A A AText only | Accessibility | Privacy and cookies

Browse site A to Z

Search results

Go To Advanced Search

Enfortumab-Vedotin-Pembrolizumab

Description
Chemotherapy Protocol UROTHELIAL CANCER Enfortumab vedotin-Pembrolizumab (EV-P) Regimen • Urothelial – Enfortumab vedotin - Pembrolizumab Indication • First-line treatment of adult patients
Url
/Media/UHS-website-2019/Docs/Chemotherapy-SOPs1/Bladdercancer/Enfortumab-Vedotin-Pembrolizumab.pdf

Ibrutinib-Venetoclax

Description
Chemotherapy Protocol Chronic Lymphocytic Leukaemia IBRUTINIB-VENETOCLAX Regimen CLL – Ibrutinib & Venetoclax Indication • Ibrutinib plus Venetoclax is recommended as an option for untreated chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) in adults. • All the criteria as described in the appropriate Blueteq form are met and an application for use has been approved. Toxicity Drug Ibrutinib Venetoclax Adverse Effect Diarrhoea, fatigue, arthralgia, musculoskeletal pain, upper respiratory tract infection, bruising, rash, nausea, pyrexia, neutropenia, thrombocytopenia, constipation, atrial fibrillation, ventricular tachycardia, hypertension, onycholclasis Upper respiratory tract infection, neutropenia, anaemia, hyperphosphataemia, electrolyte disturbances, tumour lysis syndrome (TLS), gastrointestinal disturbance, raised blood creatinine, fatigue. The adverse effects listed are no exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Pre-assessment and monitoring • Confirm immunophenotype or histology prior to administration of therapy. • Record stage of disease and TLS risk - CT scan (neck, chest, abdomen, and pelvis), B symptoms, cytopenias, clinical extent of disease. • Blood tests - FBC, DAT, U&Es, LDH, G6PD (in at risk population), urate, calcium, magnesium, creatinine, phosphate, LFTs, glucose, IGs, β2 microglobulin, hepatitis B core antibody and hepatitis B surface antigen, hepatitis C antibody, HIV 1+2 after consent. • FBC, U+Es, LFTs before each cycle, extending to 3 monthly from cycle 5 onward for clinically stable patients. • Genetic tests for 17p deletion, TP53 mutation, and IGHV mutation status. • Urine pregnancy test is required before first cycle of chemotherapy in women of childbearing age unless they are post-menopausal, have been sterilised or undergone a hysterectomy. Version 1.1 (April 2025) Page 1 of 13 CLL- Ibrutinib with Venetoclax • ECG +/- ECHO and baseline BP in all patients with a cardiac history or at risk of cardiac complications (hypertension, smokers, diabetes). • Record height and weight & ECOG performance status. • Consent and counselling - ensure patient has received adequate verbal and written information regarding their disease, treatment, and potential side effects. Document in medical notes all information that has been given. Obtain written consent prior to treatment. • Treatment should be agreed in the relevant MDT. • Document baseline and pre cycle 4 tumour lysis syndrome (TLS) risk in Aria journal. • Patients at high baseline TLS risk due to tumour bulk should be re-assessed with further CT imaging before cycle 4. • Use caution initiating with severe thrombocytopenia and consider platelet support if needed. Dose Modifications Please discuss all dose reductions / delays with the relevant consultant before prescribing if appropriate. The approach may be different depending on the clinical circumstances. The following is a general guide only. Dose adjustment may be necessary for other toxicities as well. If a patient discontinues either ibrutinib or venetoclax for reasons other than disease progression, the other drug should be continued, unless otherwise indicated by the treating consultant (up to max. 15 cycles of ibrutinib and max. 12 cycles of venetoclax). Haematological Consider blood transfusion or the use of erythropoietin according to NICE TA323 if patient symptomatic of anaemia or has haemoglobin of less than 8g/dL (80g/L). Haematological Toxicity Grade 3 neutropenia (ANC 30 mL/min CrCl 25 x 109/L High risk Any LN ≥10cm OR any LN ≥5cm AND ALC > 25 x 109/L Hydrationa PO + allopurinolb Hydrationa PO + allopurinolb a. 1.5 to 2L of water each day 2 days prior to treatment initiation, on cycle 1 day 1 and during venetoclax dose-titration phase. IV fluids may be considered based on overall TLS risk or for those who cannot maintain an adequate level of oral hydration. b. Start allopurinol 72 hours prior to initiation of venetoclax. Reduce dose to 100mg OD if CrCl < 20mL/min. Hydrationa PO and IV + allopurinolb + rasburicasec c. Consider Rasburicase 3mg IV over 30 minutes prior to dosing on day 1 and day 8 if uric acid raised. Omit allopurinol on the days of rasburicase. Monitoring for TLS Low risk Outpatient • For first dose of 20mg and 50 mg: Pre-dose, 6 to 8 hours, 24 hours • For subsequent dose increases: Pre-dose only Moderate risk Outpatient or Ambulatory care • For first dose of 20mg and 50 mg: Pre-dose, 6 to 8 hours, 24 hours • For subsequent dose increases: Pre-dose only • For first dose of 20 mg and 50 mg with additional risk (e.g., age, CrCl <80ml/min): consider High risk monitoring pathway High risk Ambulatory care or Inpatient Ambulatory/In hospital • For first dose of 20 mg and 50 mg: Pre-dose, 8, 24 hours and consider 4 and 12 hours if additional risk (e.g., age, CrCl <80ml/min) Outpatient • For subsequent dose increases: Pre-dose, 6 to 8 hours, 24 hours [TLS=Tumour Lysis Syndrome, LN=Lymph Node, ALC=Absolute Lymphocyte Count] • Cycle 1: Low, moderate and high-risk TLS patients: TLS management usually only requires oral hydration and allopurinol. TLS bloods monitoring is not required for the majority of patients, unless specifically indicated otherwise by treating clinician. • TLS risk reduces following initial 3 cycles of ibrutinib lead-in therapy. Based on the current clinical data, <2% patients remain in high-risk category at the start of cycle 4. Version 1.1 (April 2025) Page 5 of 13 CLL- Ibrutinib with Venetoclax Table 1: Venetoclax dose modifications for TLS and other toxicities Dose at interruption Restarting dosea 400mg 300mg 300mg 200mg 200mg 100mg 100mg 50mg 50mg 20mg 20mg 10mg aThe modified dose should be continued for 1 week before increasing the dose. Additional Information • The National Patient Safety Alert on Oral Systemic Anti-Cancer Therapy (NPSA/2008/RRR001) must be followed in relation to ibrutinib and venetoclax. • It must be made clear to all staff, including those in the community, that venetoclax and ibrutinib should only be prescribed under the supervision of a consultant haematologist or oncologist. • Cases of ventricular tachyarrhythmia have been reported. Temporarily discontinue ibrutinib in patients who develop symptoms suggestive of ventricular arrhythmia, including palpitations, chest pain, dyspnoea, dizziness, or fainting, and assess benefitrisk before restarting therapy. • Consider change of angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blocker (ARBs) to alternative treatments given possible risk of sudden death. • Ibrutinib should be withheld at least 3 to 7 days pre- and post-surgery, depending upon the type of surgery and the risk of bleeding. There is little data around venetoclax and surgery. It may be reasonable to stop venetoclax with ibrutinib. • Ibrutinib and venetoclax are primarily metabolized by Cytochrome P450 3A4 (CYP3A). Please refer to Summary of Product Characteristics (SmPC) to check relevant drug interactions (i.e., CYP3A inhibitors/inducers and P-gp/BCRP substrates and inhibitors) and recommended dose modifications. • Co-administration of grapefruit and grapefruit juice, Seville oranges and starfruit (carambola), should be avoided during treatment with ibrutinib and venetoclax. Additional Therapy • Antiemetics As take-home medication - metoclopramide 10mg three times a day when required oral for Cycle 1 only • Patients should be adequately hydrated during the venetoclax dose-titration phase to reduce the risk of TLS. Patients should be instructed to drink 1.5 to 2L of water daily, 2 days prior to and the days of dosing at initiation and each subsequent dose increase. Version 1.1 (April 2025) Page 6 of 13 CLL- Ibrutinib with Venetoclax Intravenous fluids should be administered as indicated based on overall risk of TLS or for those who cannot maintain an adequate level of oral hydration. • Allopurinol 300mg once a day oral for 7 days (ibrutinib initiation in Cycle 1). Then it should start 72 hours prior to the initiation of venetoclax in Cycle 4 and for 5 weeks continuously including the first week of Cycle 5 unless otherwise indicated in TLS risk assessment. • Anti-infective prophylaxis for duration of treatment: - Aciclovir 400mg twice a day oral - Co-trimoxazole 960mg once a day on Monday, Wednesday, and Friday only • Oral loperamide 4mg at the onset of diarrhoea followed by 2-4mg after each each loose stool (maximum 16mg/24 hours). • Consider growth factor at the discretion of treating clinician, when clinically indicated according to local formulary choice. For example: - Filgrastim or bioequivalent 30 million units once a day subcutaneous - Lenograstim or bioequivalent 33.6 million units once a day subcutaneous - Pegfilgrastim or bioequivalent 6mg once only subcutaneous References 1. Janssen-Cilag Ltd. Imbruvica® (ibrutinib) 140mg film-coated tablets. Summary of Product Characteristics (SmPC). Last updated 14/04/2023. Available at http://www.medicines.org.uk/emc 2. AbbVie Ltd. Venclyxto® (venetoclax) 10mg film-coated tablets (Great Britain). Summary of Product Characteristics (SmPC). Last updated 31/01/2023. Available at http://www.medicines.org.uk/emc 3. MHRA. Ibrutinib (Imbruvica▼): reports of ventricular tachyarrhythmia; risk of hepatitis B reactivation and of opportunistic infections. Drug Safety Update volume 11 issue 1, August 2017: 1. Published 15/08/2017 4. MHRA. Venetoclax (Venclyxto▼): updated recommendations on tumour lysis syndrome (TLS). Drug Safety Update volume 15, issue 5: December 2021: 2. Published 10/12/2021 5. NICE GID-TA10746. Final draft guidance – Ibrutinib with venetoclax for untreated chronic lymphocytic leukaemia. Published 21/04/2023. Last updated 21/04/2023. Available at https://www.nice.org.uk/guidance/gidta10746/documents/final-appraisal-determination-document 6. 6. Munir, Talha, et al. Chronic lymphocytic leukemia therapy guided by measurable residual disease. N Engl J Med. 2024; 390(4), 326-337. 7. Kater AP, Owen C, Moreno C, et al. Fixed-duration ibrutinib-venetoclax in patients with chronic lymphocytic leukemia and comorbidities. N Engl J Med. Published online May 13, 2022. doi:10.1056/EVIDoa2200006 7. 8. Tam S, et al. Fixed-duration ibrutinib plus venetoclax for first-line treatment of CLL: primary analysis of the CAPTIVATE FD cohort. Blood. 2022;139(22), 3278–3289. 8. 9. Moreno C, et al. Fixed-duration (FD) Ibrutinib + Venetoclax For First-line Treatment of Chronic Lymphocytic Leukemia(CLL)/Small Lymphocytic Lymphoma (SLL): 3-year Follow-up From The Phase 2 Captivate Study FD Cohort. 2022; EHA2022 357531; P669. 10. Munir T, et al. Sudden or cardiac deaths on ibrutinib-based therapy were associated with a prior history or hypertension or cardiac disease and the use of ACE-inhibitors at study entry: analysis from the Phase lll NCRI FLAIR trial. Blood. 2021; 138(1), P2636. 11. NSSG Chemotherapy Protocol (oxford-haematology.org.uk) With thanks to Dr Toby Eyre and OUH pharmacy team; used and altered with permission. Version 1.1 (April 2025) Page 7 of 13 CLL- Ibrutinib with Venetoclax REGIMEN SUMMARY Ibrutinib – Venetoclax Take Home Medicines Cycle 1 Day 1 1. Warning – TLS Assessment and Prevention Administration Instructions There is a risk of tumour lysis syndrome in CLL patients having this regimen. Ensure the patient has been assessed for TLS risk and documented in Journal on Aria. Please ensure the appropriate prophylaxis are prescribed and arrangements are in place to monitor the patient. For patients with high TLS risk, please prescribe rasburicase 3mg intravenous infusion in 50mL sodium chloride 0.9% over 30 minutes. 2. Warning – Check hydration status Administration Instructions Patient should be adequately hydrated prior to starting treatment with ibrutinib and venetoclax and venetoclax dosetitration phase to reduce the risk of TLS. Patients should be instructed to drink 1.5 to 2L (approximately 6-8 glasses) of water daily 2 days before, on the day of the first dose, and every time the dose is increased. Intravenous fluid should be administered as indicated based on overall risk of TLS of for those who cannot maintain an adequate level of oral hydration. 3. Warning – Consider growth factor at the discretion of treating clinician, when clinically indicated Administration Instructions The choice of G-CSF is dependent on local formulary and may include: a. Filgrastim or bioequivalent 30 million units once a day subcutaneous b. Lenofilgrastim or bioequivalent 33.6 million units once a day subcutaneous c. Pegfilgrastim or bioequivalent 6mg once only subcutaneous 4. Ibrutinib 420mg once a day for 28 days oral Administration instructions Oral Systemic Anti-Cancer Therapy Ibrutinib tablets should be swallowed whole with water at approximately the same time each day. Avoid grapefruit and grapefruit juice, and Seville oranges while on ibrutinib. Always check for drug interactions. 5. Allopurinol 300mg once a day for 7 days oral 6. Aciclovir 400mg twice a day for 28 days oral 7. Co-trimoxazole 960mg once a day on Monday, Wednesday, and Friday for 28 days oral Administration instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays, and Fridays. This may be dispensed as 480mg twice a day on Mondays, Wednesdays, and Fridays according to local practice. 8. Metoclopramide 10mg three times a day when required for the relief of nausea oral Administration instructions Please supply 28 tablets or nearest equivalent original pack size 9. Loperamide 4mg at the onset of diarrhoea followed by 2mg after each loose stool oral (maximum 16mg/ 24hours) Version 1.1 (April 2025) Page 8 of 13 CLL- Ibrutinib with Venetoclax Cycle 2 Day 1 10. Ibrutinib 420mg once a day for 28 days oral Administration instructions Oral Systemic Anti-Cancer Therapy Ibrutinib tablets should be swallowed whole with water at approximately the same time each day Avoid grapefruit and grapefruit juice, and Seville oranges while on ibrutinib. Always check for drug interactions. 11. Aciclovir 400mg twice a day for 28 days oral 12. Co-trimoxazole 960mg once a day on Monday, Wednesday, and Friday for 28 days oral Administration instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays, and Fridays. This may be dispensed as 480mg twice a day on Mondays, Wednesdays, and Fridays according to local practice. 13. Loperamide 4mg at the onset of diarrhoea followed by 2mg after each loose stool oral (maximum 16mg/ 24 hours) Cycle 3 Day 1 14. Ibrutinib 420mg once a day for 28 days oral Administration instructions Oral Systemic Anti-Cancer Therapy Ibrutinib tablets should be swallowed whole with water at approximately the same time each day. Avoid grapefruit and grapefruit juice, and Seville oranges while on ibrutinib. Always check for drug interactions. 15. Allopurinol 300mg once a day for 3 days oral Administration instruction Start 72 hours prior to the first dose of venetoclax. 16. Aciclovir 400mg twice a day for 28 days oral 17. Co-trimoxazole 960mg once a day on Monday, Wednesday, and Friday for 28 days oral Administration instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays, and Fridays. This may be dispensed as 480mg twice a day on Mondays, Wednesdays, and Fridays according to local practice. 18. Loperamide 4mg at the onset of diarrhoea followed by 2mg after each loose stool oral (maximum 16mg/ 24 hours) Cycle 4 Day 1 19. Warning – TLS Assessment and Prevention Administration Instructions There is a risk of tumour lysis syndrome in CLL patients having this regimen. Ensure the patient has been assessed for TLS risk and documented in Journal on Aria. Please ensure the appropriate prophylaxis are prescribed and arrangements are in place to monitor the patient. Version 1.1 (April 2025) Page 9 of 13 CLL- Ibrutinib with Venetoclax For patients with high TLS risk, please prescribe rasburicase 3mg intravenous infusion in 50mL sodium chloride 0.9% over 30 minutes. 20. Warning – Check hydration status Administration Instructions Patient should be adequately hydrated prior to starting treatment with ibrutinib and venetoclax and venetoclax dosetitration phase to reduce the risk of TLS. Patients should be instructed to drink 1.5 to 2L (approximately 6-8 glasses) of water daily 2 days before, on the day of the first day, and every time dose is increased. Intravenous fluid (150-200ml/hr as tolerated) should be administered as indicated based on overall risk of TLS of for those who cannot maintain an adequate level of oral hydration. 21. Ibrutinib 420mg once daily for 28 days oral Administration instructions Oral Systemic Anti-Cancer Therapy Ibrutinib tablets should be swallowed whole with water at approximately the same day each day. Avoid grapefruit and grapefruit juice, and Seville oranges while on ibrutinib. Always check for drug interactions. 22. Venetoclax 20mg once a day for 7 days oral Administration instructions Take in the morning with or just after food, or a meal. Swallow whole with a full glass of water. Venetoclax should be dispensed 24 hours prior to the administration date of each dose escalation. 23. Aciclovir 400mg twice a day for 28 days oral 24. Allopurinol 300mg once a day for 28 days oral 25. Co-trimoxazole 960mg once a day on Monday, Wednesday, and Friday for 28 days oral Administration instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays, and Fridays. This may be dispensed as 480mg twice a day on Mondays, Wednesdays, and Fridays according to local practice. 26. Loperamide 4mg at the onset of diarrhoea followed by 2mg after each loose stool oral (maximum 16mg/ 24 hours) Day 8 27. Warning – Dose escalation and hydration Administration instructions Please note this dose has been automatically escalated by ARIA. Please check the dose is appropriate for the patient. Patient should be adequately hydrated during the dose-titration phase to reduce the risk of TLS. Patients should be instructed to drink 1.5 to 2L (approximately 6-8 glasses) of water daily 2 days before, on the day of the first dose, and each subsequent dose increases. Intravenous fluid (150-200ml/hr as tolerated) should be administered as indicated based on overall risk of TLS of for those who cannot maintain an adequate level of oral hydration. 28. Venetoclax 50mg once a day for 7 days oral Administration instructions Take in the morning with or after food. Swallow whole with a full glass of water. Venetoclax should be dispensed 24 hours prior to the administration date of each dose escalation. Day 15 29. Warning – Dose escalation and hydration Administration instructions Please note this dose has been automatically escalated by ARIA. Please check the dose is appropriate for the patient. Patient should be adequately hydrated during the dose-titration phase to reduce the risk of TLS. Patients should be instructed to drink 1.5 to 2L (approximately 6-8 glasses) of water daily 2 days before, on the day of the first dose, and Version 1.1 (April 2025) Page 10 of 13 CLL- Ibrutinib with Venetoclax each subsequent dose increases. Intravenous fluid (150-200ml/hr as tolerated) should be administered as indicated based on overall risk of TLS of for those who cannot maintain an adequate level of oral hydration. 30. Venetoclax 100mg once a day for 7 days oral Administration instructions Take in the morning with or after food. Swallow whole with a full glass of water. Venetoclax should be dispensed 24 hours prior to the administration date of each dose escalation. Day 22 31. Warning – Dose escalation and hydration Administration instructions Please note this dose has been automatically escalated by ARIA. Please check the dose is appropriate for the patient. Patient should be adequately hydrated during the dose-titration phase to reduce the risk of TLS. Patients should be instructed to drink 1.5 to 2L (approximately 6-8 glasses) of water daily 2 days before, on the day of the first dose, and each subsequent dose increases. Intravenous fluid (150-200ml/hr as tolerated) should be administered as indicated based on overall risk of TLS of for those who cannot maintain an adequate level of oral hydration. 32. Venetoclax 200mg once a day for 7 days oral Administration instructions Take in the morning with or after food. Swallow whole with a full glass of water. Venetoclax should be dispensed 24 hours prior to the administration date of each dose escalation. Cycle 5 Day 1 33. Warning - Dose escalation and hydration Administration instructions Please note this dose has been automatically escalated by ARIA. Please check the dose is appropriate for the patient. Patient should be adequately hydrated during the dose-titration phase to reduce the risk of TLS. Patients should be instructed to drink 1.5 to 2L (approximately 6-8 glasses) of water daily 2 days before and on the day of the first dose, and each subsequent dose increases. Intravenous fluid (150-200ml/hr as tolerated) should be administered as indicated based on overall risk of TLS of for those who cannot maintain an adequate level of oral hydration. 34. Ibrutinib 420mg once a day for 28 days oral Administration instructions Oral Systemic Anti-Cancer Therapy Ibrutinib tablets should be swallowed whole with water at approximately the same time each day. Avoid grapefruit and grapefruit juice, and Seville oranges while on ibrutinib. Always check for drug interactions. 35. Venetoclax 400mg once a day for 28 days oral Administration instructions Take in the morning with or after food. Swallow whole with a full glass of water. Venetoclax should be dispensed 24 hours prior to the administration date of each dose escalation. 36. Aciclovir 400mg twice a day for 28 days oral 37. Allopurinol 300mg once a day for 7 days oral 38. Co-trimoxazole 960mg once a day on Monday, Wednesday, and Friday for 28 days oral Administration instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays, and Fridays. This may be dispensed as 480mg twice a day on Mondays, Wednesdays, and Fridays according to local practice. Version 1.1 (April 2025) Page 11 of 13 CLL- Ibrutinib with Venetoclax 39. Loperamide 4mg at the onset of diarrhoea followed by 2mg after each loose stool oral (maximum 16mg/ 24 hours). Cycle 6 onwards Day 1 40. Ibrutinib 420mg once a day for 28 days oral Administration instructions Oral Systemic Anti-Cancer Therapy Ibrutinib tablets should be swallowed whole with water at approximately the same time each day. Avoid grapefruit and grapefruit juice, and Seville oranges while on ibrutinib. Always check for drug interactions. 41. Venetoclax 400mg once a day for 28 days oral Administration instructions Take in the morning with or after food. Swallow whole with a full glass of water. 42. Aciclovir 400mg twice a day for 28 days oral 43. Co-trimoxazole 960mg once a day on Monday, Wednesday, and Friday for 28 days oral Administration instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays, and Fridays. This may be dispensed as 480mg twice a day on Mondays, Wednesdays, and Fridays according to local practice. 44. Loperamide 4mg at the onset of diarrhoea followed by 2mg after each loose stool oral (maximum 16mg/ 24 hours) Version 1.1 (April 2025) Page 12 of 13 CLL- Ibrutinib with Venetoclax DOCUMENT CONTROL Version Date Amendment Written By Approved By Heading changed from monitoring to pre-assessment and monitoring Hydration route updated in TLS 1.1 April 2025 risk assessment flow chart Infusion rate of IV fluid removed Aram Shortland Dr David Dutton Pharmacist Consultant haematologist in TLS risk assessment flow chart and regimen summary Growth factor added as warning in regimen summary Alexandre Guedes 1 September 2023 None Pharmacist Aram Shortland Dr David Dutton Consultant haematologist Pharmacist This chemotherapy protocol has been developed as part of the chemotherapy electronic prescribing project. This was and remains a collaborative project that originated from the former CSCCN. These documents have been approved on behalf of the following Trusts; Hampshire Hospitals NHS Foundation Trust Isle of Wight NHS Trust Portsmouth Hospitals NHS Trust Salisbury NHS Foundation Trust University Hospital Southampton NHS Foundation Trust Western Sussex Hospitals NHS Foundation Trust All actions have been taken to ensure these protocols are correct. However, no responsibility can be taken for errors which occur as a result of following these guidelines. Version 1.1 (April 2025) Page 13 of 13 CLL- Ibrutinib with Venetoclax
Url
/Media/UHS-website-2019/Docs/Chemotherapy-SOPs1/CLL/Ibrutinib-Venetoclax-Ver1.1.pdf

Carboplatin-Docetaxel-Pertuzumab-Trastuzumab_IV-SC

Description
Chemotherapy Protocol BREAST CANCER CARBOPLATIN (AUC6)-DOCETAXEL- PERTUZUMABTRASTUZUMAB (IV/SC) Regimen • Breast Cancer – Carboplatin (AUC6)-Docetaxel-Pertuzumab-Trastuzumab (IV/SC) Indication
Url
/Media/UHS-website-2019/Docs/Chemotherapy-SOPs1/Breastcancer/Carboplatin-Docetaxel-Pertuzumab-Trastuzumab-IV-SC.pdf

EC-DPH IV (Cyclophosphamide-Epirubicin-Docetaxel-Pertuzumab-Trastuzumab IV)

Description
Please refer to the most up to date Bluteq eligibility criteria for pertuzumab and trastuzumab before prescribing.
Url
/Media/UHS-website-2019/Docs/Chemotherapy-SOPs1/Breastcancer/EC-DPH-IV-Cyclophosphamide-Epirubicin-Docetaxel-Pertuzumab-Trastuzumab-IV.pdf

Carboplatin-Docetaxel-Pertuzumab-Trastuzumab_IV

Description
Chemotherapy Protocol BREAST CANCER CARBOPLATIN (AUC 6)-DOCETAXEL-PERTUZUMABTRASTUZUMAB (IV) Regimen • Breast Cancer – Carboplatin (AUC6)-Docetaxel-Pertuzumab-Trastuzumab (IV) Indication • Neo-Adjuvant treatment of high risk (node positive or negative tumour greater than or equal to one centimetre) HER2 positive breast cancer that that is locally advanced, inflammatory, or early-stage with a high risk of recurrence, in adults. • WHO Performance status 0, 1, 2 Toxicity Drug Carboplatin Docetaxel Pertuzumab Trastuzumab Adverse Effect Neuropathy, nephrotoxicity, ototoxicity, thrombocytopenia Hypersensitivity, fluid retention, neuropathy, joint pains, nail changes, fatigue, alopecia, neutropenia Diarrhoea, hypersensitivity reactions, headache, reduced appetite, dyspnoea, cough, vomiting, nausea, constipation, rash, pain, oedema, fatigue, asthenia, cardiotoxicity Cardiotoxicity, acute respiratory distress syndrome, infusion related effects The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Monitoring Regimen • FBC, U&E’s and LFT’s prior to each cycle • EDTA or calculated creatinine clearance before the first cycle • HER2 status prior to initiating therapy • Cardiac function must be assessed prior to starting treatment. Thereafter, cardiac function should be assessed every 9-12 weeks and as clinically indicated. • Blood pressure prior to each trastuzumab administration Version 1.3 (July 2024) Page 1 of 14 Breast –Carboplatin (AUC6)-Docetaxel-Pertuzumab-Trastuzumab (IV) Dose Modifications The dose modifications listed are for haematological, liver and renal function only. Dose adjustments may be necessary for other toxicities as well. In principle all dose reductions due to adverse drug reactions should not be reescalated in subsequent cycles without consultant approval. It is also a general rule for chemotherapy that if a third dose reduction is necessary treatment should be stopped. Please discuss all dose reductions / delays with the relevant consultant before prescribing, if appropriate. The approach may be different depending on the clinical circumstances. This is especially true in the adjuvant / neoadjuvant setting where dose delays and reductions may be less appropriate. The following is a general guide only. Haematological Prior to prescribing the following treatment criteria must be met; Criteria Neutrophils Platelets Eligible Level equal to or more than 1x109/L equal to or more than 100x109/L Consider blood transfusion if patient symptomatic of anaemia or has a haemoglobin of less than 8g/dL (80g/L) If counts on day one are below these criteria for neutrophil and/or platelets then delay carboplatin and docetaxel treatment for seven days. Only re-start treatment when these levels are reached. If patients experience a febrile neutropenia or a treatment delay due to neutrophil count of less than 0.5 x109/L or platelets less than 50 x109/L for more than seven days, then reduce the dose of carboplatin and docetaxel to 80% of the original dose. If the neutropenia or thrombocytopenia recurs despite this decrease in dose intensity, the dose should either be further reduced to 50% of the original dose or treatment stopped. Haematological dose modifications are not necessary for pertuzumab or trastuzumab. If patients do not tolerate either pertuzumab or trastuzumab, treatment should be stopped. The haematological modifications refer to carboplatin and docetaxel only. Version 1.3 (July 2024) Page 2 of 14 Breast –Carboplatin (AUC6)-Docetaxel-Pertuzumab-Trastuzumab (IV) Liver Impairment Drug Carboplatin Docetaxel Pertuzumab Bilirubin (μmol/L) AST/ALT (units) Alk Phos (units) No dose adjustment needed Dose (% of original dose) N/A 1.5xULN or greater and 2.5xULN or greater Consider 75% Greater than ULN and/or 3.5xULN or greater and 6xULN or greater Not Recommended The safety and efficacy of pertuzumab has not been established in hepatic impairment Trastuzumab No dose adjustment needed Renal Impairment Drug Carboplatin Docetaxel Pertuzumab Trastuzumab Creatinine Clearance (ml/min) 20ml/min or less Dose (% of original dose) Contra-indicated No dose adjustment necessary No dose adjustment necessary in mild to moderate renal impairment. No information in severe renal impairment – clinical decision No dose adjustment necessary Other Dose reductions or interruptions in therapy are not necessary for those toxicities that are considered unlikely to be serious or life threatening. For example, alopecia, altered taste or nail changes. Docetaxel Peripheral neuropathy at NCI-CTC grade 3 should result in a dose reduction from 75mg/m2 to 60mg/m2. If the NCI-CTC grade 3 neuropathy occurred at doses lower than 75mg/m2 or a NCI-CTC grade 4 toxicity develops stop treatment. Excessive tearing / lacrimation are related to cumulative docetaxel doses and occur after a median of 400mg/m². Symptomatic treatment with hypromellose 0.3% eye drops four times a day may help. However, if the ocular irritation continues reduce the docetaxel dose to 60mg/m2 in the first instance. Delay the docetaxel where a NCI-CTC grade 3 cutaneous toxicity is present on day one of the cycle until it resolves to NCI-CTC grade 1 or below. The subsequent doses of docetaxel should be reduced to from 75mg/m2 to 60mg/m2. If it occurs with a dose of 60mg/m2 or if there is no recovery after two weeks, docetaxel treatment should be stopped. Where a NCI-CTC grade 3 cutaneous toxicity occurs between Version 1.3 (July 2024) Page 3 of 14 Breast –Carboplatin (AUC6)-Docetaxel-Pertuzumab-Trastuzumab (IV) cycles with recovery by day one then reduce the docetaxel dose as described. Docetaxel should be stopped in response to a NCI-CTC grade 4 cutaneous toxicity. Pertuzumab The diarrhoea can be severe in patients treated with pertuzumab. It is important to ensure patients are given appropriate therapy for the treatment of diarrhoea. This is not included in the regimen on ARIA and must be added from the support folder. Pertuzumab and Trastuzumab Cardiac The LVEF should be fifty or above before starting cycle one of pertuzumab and trastuzumab. Subsequent Echocardiograms The flow chart below describes the process to be followed if there is an asymptomatic decline in LVEF during pertuzumab and trastuzumab treatment. This is taken from the study protocol as used in the reference section. Study treatment refers to pertuzumab and trastuzumab. The LVEF should be fifty or above before starting cycle one of trastuzumab. Version 1.3 (July 2024) Page 4 of 14 Breast –Carboplatin (AUC6)-Docetaxel-Pertuzumab-Trastuzumab (IV) In general patients who develop symptomatic cardiac dysfunction should have pertuzumab and trastuzumab discontinued, be commenced on ACE inhibitor therapy and be referred to a cardiologist. Further treatment should be discussed with the relevant oncology consultant.. Regimen The starting dose of carboplatin AUC6 is used with calculated GFR. AUC 5 may be considered with EDTA clearance, seek advice from the appropriate consultant before prescribing. The recommended maximum dose when using a calculated creatinine clearance at AUC 6 is 900mg (this will set as 890mg to match the national dose bands). If you have an obese patient or an individual with a calculated creatinine clearance above 125ml/min please seek advice from the relevant consultant. It should be noted that the dose of carboplatin may need to be altered if there is a change (improvement or reduction) in renal function of more than 10% from the previous cycle. Docetaxel is highly myelosuppressive and in those with poor bone marrow reserves (for example due to extensive prior treatment, bone metastasis or extensive skeletal radiation) consider a starting dose of 55mg/m² with a view to increase to 75mg/m² if well tolerated. Version 1.3 (July 2024) Page 5 of 14 Breast –Carboplatin (AUC6)-Docetaxel-Pertuzumab-Trastuzumab (IV) 21 day cycle for 6 cycles. Trastuzumab is then continued post surgery as monotherapy for a further 12 cycles (18 cycles of treatment in total) Cycle 1 Drug Carboplatin Docetaxel Dose AUC 6 (max dose) 75mg/m2 Pertuzumab 840mg Trastuzumab 8mg/kg Days 2 2 1 1 Administration Intravenous infusion in 500ml glucose 5% over 60 minutes Intravenous infusion in 250ml sodium chloride 0.9% over 60 minutes Intravenous infusion in 250ml sodium chloride 0.9% over 60 minutes Intravenous infusion in 250ml sodium chloride 0.9% over 90 minutes Cycle 2, 3, 4, 5, 6 Drug Dose Carboplatin Docetaxel AUC 6 (maximum dose) 75mg/m2 Pertuzumab 420mg Trastuzumab 6mg/kg Days Administration 1 Intravenous infusion in 500ml glucose 5% over 60 minutes 1 Intravenous infusion in 250ml sodium chloride 0.9% over 60 minutes 1 Intravenous infusion in 250ml sodium chloride 0.9% over 60 minutes 1 Intravenous infusion in 250ml sodium chloride 0.9% over 90 minutes Cycle 7 – 18 (12 cycles will be set in ARIA) Drug Dose Days Administration Trastuzumab 6mg/kg 1 Intravenous infusion in 250ml sodium chloride 0.9% over 90 minutes Dose Information • Carboplatin will be dose banded in accordance with the national dose bands • The maximum dose of carboplatin for AUC 6 is 900mg (this will be set as 890mg to comply with national dose bands) • Docetaxel will be dose banded according to the national dose bands (20mg/ml) • Docetaxel induced fluid retention can lead to weight gain. This is not a reason to alter the doses Version 1.3 (July 2024) Page 6 of 14 Breast –Carboplatin (AUC6)-Docetaxel-Pertuzumab-Trastuzumab (IV) • If the time between two sequential infusions of pertuzumab is less than six weeks, the 420mg dose should be administered as soon as possible without regard to the next planned dose. If the time between two sequential infusions is 6 weeks or more, the initial loading dose of 840mg should be re-administered as a 60 minute intravenous infusion followed every 3 weeks thereafter by a maintenance dose of 420 mg administered over a period of 30 to 60 minutes. • Intravenous trastuzumab will be dose banded in accordance with national dose bands (21mg/ml) • If the patient misses a dose of intravenous trastuzumab by seven days or less, then the usual maintenance dose of 6mg/kg should be given as soon as possible. Do not wait until the next planned cycle. Subsequent maintenance doses should be given according to the previous schedule • If the patient misses a dose of intravenous trastuzumab by more than seven days, a re-loading dose of 8mg/kg should be given over 90 minutes. Subsequent maintenance doses should then be given every 21 days from that point Administration Information • Hypersensitivity reactions tend to occur with the first or second infusion of docetaxel. The docetaxel infusion should not be interrupted for minor symptoms such as flushing or localised rashes. Immediately discontinue the infusion for severe reactions which include profound hypotension, bronchospasm and generalised erythema. • Docetaxel doses of more than 200mg should be diluted in 500ml sodium chloride 0.9% (maximum concentration 0.74mg/ml) • Pertuzumab has been associated with hypersensitivity and infusion related reactions. Patients should be observed for 60 minutes after the first infusion and for 30 minutes after the second infusion, provided no reaction occurred on the first infusion. If patients have tolerated the first two infusions with no infusion related reactions consideration can be given to eliminating this observation period. • Intravenous trastuzumab is associated with hypersensitivity reactions. Patients should be observed for six hours following the start of the first infusion of trastuzumab and for two hours following the start of the second infusion. If the patient has tolerated the first two infusions with no infusion related effects consideration can be given to eliminating this observation period. • The first infusion of intravenous trastuzumab must be administered over 90 minutes. If this is well tolerated administer subsequent infusions over 30 minutes Extravasation • Carboplatin - irritant • Docetaxel – vesicant • Pertuzumab - neutral Version 1.3 (July 2024) Page 7 of 14 Breast –Carboplatin (AUC6)-Docetaxel-Pertuzumab-Trastuzumab (IV) • Trastuzumab (intravenous) – neutral Additional Therapy • Antiemetics 15-30 minutes before chemotherapy - ondansetron 8mg oral or intravenous As take home medication - metoclopramide 10mg three times a day when required oral - ondansetron 8mg twice a day for three days oral • To prevent fluid retention and hypersensitivity reactions prescribe dexamethasone 8mg twice a day oral for three days starting 24 hours before the docetaxel administration. On the occasions where individuals attend for treatment and have forgotten to take the dexamethasone pre-medication administer dexamethasone 20mg once only dose intravenous bolus. • Diarrhoea is a common adverse effect, particularly on cycle one. Consider prescribing loperamide 4mg after the first loose motion then 2mg after each loose motion thereafter. This is included on cycle one only and can be added from the support folder thereafter • For treatment of pertuzumab or trastuzumab infusion reactions ‘once only when required’ doses of the following should be prescribed; - chlorphenamine 10mg intravenous - hydrocortisone 100mg intravenous - paracetamol 1000mg oral • Growth factors according to local formulary choice. For example: - filgrastim or bioequivalent 30million units once a day for 7 days starting from day 3 subcutaneous - lenograstim or bioequivalent 33.6million units once a day for 7 days starting from day 3 subcutaneous - pegfilgrastim or bioequivalent 6mg once only on day 2 subcutaneous • Gastric protection with a proton pump inhibitor or a H2 antagonist may be considered in patients considered at high risk of GI ulceration or bleed References 1.Valero V, Forbes J, Pegram MD et al. Multicentre phase III randomised trial comparing docetaxel and trastuzumab with docetaxel, carboplatin and trastuzumab as first line chemotherapy for patients with HER2 positive gene amplified metastatic breast cancer (BCIRG007 study); two highly active therapeutic regimens. J Clin Oncol 2011; 29 (2): 149156. 2.Baselga J, Cortes J, Sung-Bae K et al. Peruzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012; 366 (2): 109-11 Version 1.3 (July 2024) Page 8 of 14 Breast –Carboplatin (AUC6)-Docetaxel-Pertuzumab-Trastuzumab (IV) REGIMEN SUMMARY Carboplatin (AUC6)-Docetaxel-Pertuzumab-Trastuzumab (IV) Cycle 1 Day One 1. Dexamethasone 8mg twice a day oral (from TTO)* Administration Instructions Ensure the patient has taken the dexamethasone pre-medication the day before and the day of docetaxel administration (and the day after). On the occasions where individuals attend for treatment and have forgotten to take the dexamethasone pre-medication administer dexamethasone 20mg (or equivalent dose) IV stat 15-30 minutes before chemotherapy. If the patient has already taken a dose of dexamethasone do not administer this dose 2. Pertuzumab 840mg intravenous infusion in 250ml sodium chloride 0.9% over 60 minutes Administration Instructions The first infusion of pertuzumab should be given over 60 minutes. If this is well tolerated subsequent infusions may be given over 30 minutes 3. Trastuzumab 8mg/kg intravenous infusion in 250ml sodium chloride 0.9% over 90 minutes Administration Instructions The first infusion of trastuzumab must be administered over 90 minutes. If this is well tolerated administer subsequent infusions over 30 minutes 4. Chlorphenamine 10mg intravenous when required for infusion related reactions 5. Hydrocortisone 100mg intravenous when required for infusion related reactions 6. Paracetamol 1000mg oral when required for infusion related reactions Administration Instructions Please check if the patient has taken paracetamol. Maximum dose is 4g per 24 hours. There should be 4 hours between doses Day Two 7. Dexamethasone 8mg twice a day oral (from TTO)* Administration Instructions Ensure the patient has taken the dexamethasone pre-medication the day before and the day of docetaxel administration (and the day after). On the occasions where individuals attend for treatment and have forgotten to take the dexamethasone pre-medication administer dexamethasone 20mg (or equivalent dose) IV stat 1530 minutes before chemotherapy. If the patient has already taken a dose of dexamethasone do not administer this dose 8. Ondansetron 8mg oral or intravenous Administration Instructions Administer 15-30 minutes prior to SACT. This may be given as 8mg intravenous if required 9. Docetaxel 75mg/m² intravenous infusion in 250ml sodium chloride 0.9% over 60 minutes Administration Instructions Ensure the patient has taken the dexamethasone pre-medication the day before and the day of docetaxel administration (and the day after). On the occasions where individuals attend for treatment and have forgotten to take the dexamethasone pre-medication administer dexamethasone 20mg (or equivalent dose) IV stat 1530 minutes before chemotherapy. If the patient has already taken a dose of dexamethasone do not administer this dose Version 1.3 (July 2024) Page 9 of 14 Breast –Carboplatin (AUC6)-Docetaxel-Pertuzumab-Trastuzumab (IV) 10. Carboplatin AUC6 intravenous infusion in 500ml glucose 5% over 60 minutes Administration Instructions This recommended maximum dose is 900mg based on a creatinine clearance of 125ml/min. This will be set at 890mg in ARIA to comply with national dose bands Take Home Medicines (given on day 1) 11. Dexamethasone 8mg twice a day oral for 3 days starting the day before the docetaxel infusion. Administration Instructions This is the supply for the next cycle. Take in the morning and at lunchtime 12. Metoclopramide 10mg three times a day when required oral Administration Instructions Please supply 28x10mg tablets or nearest equivalent pack size 13. Ondansetron 8mg twice a day for 3 days starting on the evening of the day of chemotherapy (not antibody) administration oral Administration Instructions Start on the evening of the day of chemotherapy (not antibody administration) 14. Loperamide 4mg after the first loose stool and 2mg after each subsequent loose stool to a maximum of 16mg in 24 hours Administration Instructions Take 4mg after the first loose stool and then 2mg after each subsequent loose stool to a maximum of 16mg in 24 hours. Please supply one original pack size 15. Growth factor according to local formulary choice Administration Instructions Growth factors according to local formulary choice. For example; - filgrastim or bioequivalent 30million units once a day for 7 days starting from day 3 subcutaneous - lenograstim or bioequivalent 33.6million units once a day for 7 days starting from day 3 subcutaneous - pegfilgrastim or bioequivalent 6mg once only on day 2 subcutaneous Cycles 2, 3, 4, 5 Day One 16. Pertuzumab 420mg intravenous infusion in 250ml sodium chloride 0.9% over 60 minutes Administration Instructions The first infusion of pertuzumab should be given over 60 minutes. If this is well tolerated subsequent infusions may be given over 30 minutes 17. Trastuzumab 6mg/kg intravenous infusion in 250ml sodium chloride 0.9% over 90 minutes Administration Instructions The first infusion of trastuzumab must be administered over 90 minutes. If this is well tolerated administer subsequent infusions over 30 minutes 18. Ondansetron 8mg oral or intravenous Administration Instructions Administer 15-30 minutes prior to SACT. This may be given as 8mg intravenous if required 19. Docetaxel 75mg/m² intravenous infusion in 250ml sodium chloride 0.9% over 60 minutes Administration Instructions Ensure the patient has taken the dexamethasone pre-medication the day before and the day of docetaxel administration (and the day after). On the occasions where individuals attend for treatment and have forgotten to take the dexamethasone pre-medication administer dexamethasone 20mg (or equivalent dose) IV stat 15-30 minutes before chemotherapy. If the patient has already taken a dose of dexamethasone do not administer this dose Version 1.3 (July 2024) Page 10 of 14 Breast –Carboplatin (AUC6)-Docetaxel-Pertuzumab-Trastuzumab (IV) 20. Carboplatin AUC 6 intravenous infusion in 500ml glucose 5% over 60 minutes Administration Instructions This recommended maximum dose is 900mg based on a creatinine clearance of 125ml/min. This will be set at 890mg in ARIA to comply with national dose bands 21. Chlorphenamine 10mg intravenous when required for infusion related reactions 22. Hydrocortisone 100mg intravenous when required for infusion related reactions 23. Paracetamol 1000mg oral when required for infusion related reactions Administration Instructions Please check if the patient has taken paracetamol. Maximum dose is 4g per 24 hours. There should be 4 hours between doses Take Home Medicines 24. Dexamethasone 8mg twice a day oral for 3 days starting the day before the docetaxel infusion. Administration Instructions This is the supply for the next cycle. Take in the morning and lunchtime 25. Metoclopramide 10mg three times a day when required oral Administration Instructions Please supply 28x10mg tablets or nearest equivalent pack size 26. Ondansetron 8mg twice a day for 3 days starting on the evening of the day of chemotherapy (not antibody) administration oral Administration Instructions Start on the evening of the day of chemotherapy (not antibody administration) 27. Growth factor according to local formulary choice Administration Instructions Growth factors according to local formulary choice. For example; -filgrastim or bioequivalent 30million units once a day for 7 days starting from day 3 subcutaneous -lenograstim or bioequivalent 33.6million units once a day for 7 days starting from day 3 subcutaneous -pegfilgrastim or bioequivalent 6mg once only on day 2 subcutaneous Cycle 6 Day One 28. Pertuzumab 420mg intravenous infusion in 250ml sodium chloride 0.9% over 60 minutes Administration Instructions The first infusion of pertuzumab should be given over 60 minutes. If this is well tolerated subsequent infusions may be given over 30 minutes 29. Trastuzumab 6mg/kg intravenous infusion in 250ml sodium chloride 0.9% over 90 minutes Administration Instructions The first infusion of trastuzumab must be administered over 90 minutes. If this is well tolerated administer subsequent infusions over 30 minutes 30. Ondansetron 8mg oral or intravenous Administration Instructions Administer 15-30 minutes prior to SACT. This may be given as 8mg intravenous if required Version 1.3 (July 2024) Page 11 of 14 Breast –Carboplatin (AUC6)-Docetaxel-Pertuzumab-Trastuzumab (IV) 31. Docetaxel 75mg/m² intravenous infusion in 250ml sodium chloride 0.9% over 60 minutes Administration Instructions Ensure the patient has taken the dexamethasone pre-medication the day before and the day of docetaxel administration (and the day after). On the occasions where individuals attend for treatment and have forgotten to take the dexamethasone pre-medication administer dexamethasone 20mg (or equivalent dose) IV stat 15-30 minutes before chemotherapy. If the patient has already taken a dose of dexamethasone do not administer this dose 32. Carboplatin AUC6 intravenous infusion in 500ml glucose 5% over 60 minutes Administration Instructions This recommended maximum dose is 900mg based on a creatinine clearance of 125ml/min. This will be set at 890mg in ARIA to comply with national dose bands 33. Chlorphenamine 10mg intravenous when required for infusion related reactions 34. Hydrocortisone 100mg intravenous when required for infusion related reactions 35. Paracetamol 1000mg oral when required for infusion related reactions Administration Instructions Please check if the patient has taken paracetamol. Maximum dose is 4g per 24 hours. There should be 4 hours between doses Take Home Medicines 36. Metoclopramide 10mg three times a day when required oral 37. Ondansetron 8mg twice a day starting on the evening of the day of chemotherapy (not antibody) administration oral Administration Instructions Start on the evening of the day of chemotherapy (not antibody administration) 38. Growth factor according to local formulary choice Administration Instructions Growth factors according to local formulary choice. For example; - filgrastim or bioequivalent 30million units once a day for 7 days starting from day 3 subcutaneous - lenograstim or bioequivalent 33.6million units once a day for 7 days starting from day 3 subcutaneous - pegfilgrastim or bioequivalent 6mg once only on day 2 subcutaneous Cycle 7 – 18 Day One 39. Trastuzumab 6mg/kg intravenous infusion in 250ml sodium chloride 0.9% over 90 minutes Administration Instructions The first infusion of trastuzumab must be administered over 90 minutes. If this is well tolerated administer subsequent infusions over 30 minutes. 40. Chlorphenamine 10mg intravenous when required for infusion related reactions 41. Hydrocortisone 100mg intravenous when required for infusion related reactions 42. Paracetamol 1000mg oral when required for infusion related reactions Administration Instructions Please check if the patient has taken paracetamol. Maximum dose is 4g per 24 hours. There should be 4 hours between doses Version 1.3 (July 2024) Page 12 of 14 Breast –Carboplatin (AUC6)-Docetaxel-Pertuzumab-Trastuzumab (IV) *Cycle one dexamethasone must be prescribed in advance of the chemotherapy. In Aria Planner the dexamethasone 8mg twice daily will appear on days 1, 2, 3 of treatment. This is the supply for the next cycle. The administration instructions reflect this. On the last cycle no dexamethasone will appear for prescribing. DOCUMENT CONTROL Version Date Amendment Written By Approved By 1.3 July Trastuzumab updated with national 2024 dose banding Alexandra Pritchard Pharmacist Nanda Basker Pharmacist 1.2 Aug 2022 Carboplatin dose bands changed to national dose bands Coding removed Dr Deborah Wright Donna Kimber Pharmacist Pharmacy Technician Trastuzumab missed doses changed to seven days Pertuzumab and trastuzumab observation period reduced on second and subsequent infusions Docetaxel extravasation changed to 1.1 April 2019 vesicant Ondansetron added to antiemetic regimen Dr Deborah Wright Pharmacist Rebecca Wills Pharmacist Loperamide added to TTO Growth factors added to TTO Paracetamol administration instructions added Carboplatin maximum dose added Disclaimer updated 1 July 2017 None Nanda Basker Pharmacist Dr Sanjay Raj Consultant Clinical Oncologist This chemotherapy protocol has been developed as part of the chemotherapy electronic prescribing project. This was and remains a collaborative project that originated from the former CSCCN. These documents have been approved on behalf Version 1.3 (July 2024) Page 13 of 14 Breast –Carboplatin (AUC6)-Docetaxel-Pertuzumab-Trastuzumab (IV) of the following Trusts; Hampshire Hospitals NHS Foundation Trust NHS Isle of Wight Portsmouth Hospitals NHS Trust Salisbury Hospitals NHS Foundation Trust University Hospital Southampton NHS Foundation Trust Western Sussex Hospitals NHS Foundation Trust All actions have been taken to ensure these protocols are correct. However, no responsibility can be taken for errors that occur as a result of following these guidelines. These protocols should be used in conjunction with other references such as the Summary of Product Characteristics and relevant published papers Version 1.3 (July 2024) Page 14 of 14 Breast –Carboplatin (AUC6)-Docetaxel-Pertuzumab-Trastuzumab (IV)
Url
/Media/UHS-website-2019/Docs/Chemotherapy-SOPs1/Breastcancer/Carboplatin-Docetaxel-Pertuzumab-Trastuzumab-IV.pdf

Atezolizumab-Bevacizumab

Description
Chemotherapy Protocol Hepatocellular Cancer ATEZOLIZUMAB-BEVACIZUMAB Regimen  HCC-Atezolizumab-Bevacizumab Indication  Atezolizumab in combination with bevacizumab for the first-line systemic treatment of adult patients with locally advanced or metastatic and/or unresectable hepatocellular carcinoma where the following criteria is met: - The patient has a diagnosis of hepatocellular carcinoma and that one of the following applies to the patient: 1. The patient has a confirmed histological diagnosis of hepatocellular carcinoma (HCC) 2. A biopsy is deemed to be very high risk or technically not feasible in the patient. The decision to not biopsy has been made and documented by a specialist HCC multi-disciplinary team meeting and the tumour meets the non-invasive diagnostic criteria (EASL-EORTC Clinical Practice Guidelines: Management, Journal of Hepatology 2012 vol 56 p908-943). Non-invasive criteria can only be applied to cirrhotic patients and are based on imaging techniques obtained by 4-phase multidetector CT scan or dynamic contrastenhanced MRI. Diagnosis should be based on the identification of the typical hallmark of HCC (hypervascular in the arterial phase with washout in the portal venous or delayed phases). While one imaging technique is required for nodules beyond 1cm in diameter, a more conservative approach with 2 techniques is recommended in suboptimal settings) - The patient has metastatic or locally advanced disease that is ineligible or has failed surgical or loco-regional therapies. - The patient has Child-Pugh A liver function. - The patient has not received previous systemic therapy for his/her hepatocellular carcinoma unless the combination of Atezolizumab and Bevacizumab has been received via the EAMS scheme (please note previous systemic treatment with sorafenib, Lenvatinib or regorafenib or any immunotherapy or any systemic chemotherapy is not allowed). - The patient has an ECOG performance status of 0 or 1. - The clinician is aware of the risk of variceal bleeding due to bevacizumab and will comply with the recommendation that an oesophago-gastro-duodenoscopy (OGD) be considered in patients at high risk of variceal bleeding and that all sizes of varices be assessed and treated as per local standard of care prior to treatment with atezolizumab and bevacizumab. - Treatment with atezolizumab in combination with bevacizumab will continue until loss of benefit or unacceptable toxicity or withdrawal of patient consent, whichever comes first. If either atezolizumab or bevacizumab has to be discontinued due to toxicity and the patient is otherwise benefitting from treatment, treatment should continue with the remaining agent until loss of clinical benefit or unacceptable toxicity or withdrawal of patient consent. - The patient has no symptomatically active brain metastases or leptomeningeal metastases. Version 1 Page 1 of 11 HCC-Atezolizumab-Bevacizumab - The patient has received no prior treatment with anti-PD-1, anti-PD-L1, anti-PDL2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody. - A formal medical review as to how treatment with atezolizumab in combination with bevacizumab is being tolerated and whether treatment with the combination should continue or not will be scheduled to occur at least by the end of the first 6 weeks of treatment. - If a treatment break of more than 12 weeks beyond the expected 3 weekly cycle length is needed, a treatment break form to restart treatment should be completed, including an indication as appropriate if the patient had an extended break because of COVID 19. - Upon discontinuation of the combination of atezolizumab and bevacizumab on account of loss of clinical benefit or treatment intolerance and if the patient is fit for further systemic therapy, the next line of treatment would be a choice of either sorafenib or Lenvatinib. - ECOG performance status 0, 1, 2 Toxicity Drug Atezolizumab Bevacizumab Adverse Effect Fatigue, rash, pruritis, pneumonitis, colitis, pancreatitis, diarrhoea, diabetes mellitus, adrenal insufficiency, thyroid disorders, nausea, electrolyte disturbances, hepatitis, myasthenic syndrome, Guillain Barre syndrome Haemorrhage, hypertension, proteinuria, impaired wound healing, gastrointestinal perforations, fistulae, arterial thrombosis, fatigue, diarrhoea, abdominal pain The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Monitoring Drugs  FBC, LFTs and U&Es prior to day each cycle  EDTA or calculated creatinine clearance prior to each cycle  Blood pressure and dipstick urinalysis for proteinuria prior to treatment with bevacizumab  Thyroid function tests and random cortisol prior to starting treatment and then every 6 weeks or when clinically indicated.  Random blood glucose prior to each cycle.  Prior to starting treatment screening for oesophageal varices should be performed. Dose Modifications The dose modifications listed are for haematological, liver and renal function and drug specific toxicities only. Dose adjustments may be necessary for other toxicities as well. Version 1 Page 2 of 11 HCC-Atezolizumab-Bevacizumab In principle all dose reductions due to adverse drug reactions should not be re-escalated in subsequent cycles without consultant approval. It is also a general rule for chemotherapy that if a third dose reduction is necessary treatment should be stopped. Please discuss all dose reductions / delays with the relevant consultant before prescribing, if appropriate. The approach may be different depending on the clinical circumstances. Haematological Consider blood transfusion if patient symptomatic of anaemia or has a haemoglobin of less than 8g/dL. There is little need to adjust the dose of atezolizumab or bevacizumab for haematological toxicity. Hepatic Impairment Drug Bevacizumab Bilirubin (μmol/L) N/A AST/ALT units N/A Dose No information available Atezolizumab If AST/ALT within normal limits at baseline, prior to starting treatment and increases to > 3x to ≤10xULN Or If AST/ALT is > 1 to ≤3 xULN at baseline, prior to starting treatment and increases to > 5x to ≤10xULN Withhold Atezolizumab. Treatment may be resumed when it improves to grade 0 or grade 1 within 12 weeks and corticosteroids have been reduced to ≤10mg Prednisolone or equivalent per day. Or If AST/ALT if > 3 to ≤5xULN at baseline, prior to starting treatment and increases to > 8 to ≤10xULN If AST/ALT increases to > 10x ULN Or Permanently discontinue atezolizumab. Total bilirubin increases to > 3xULN No initial dose adjustment of atezolizumab is required for mild or moderate hepatic impairment. There is only very limited data for HCC patients with Child-Pugh B liver disease and currently no data available for Child-Pugh C liver disease patients. Version 1 Page 3 of 11 HCC-Atezolizumab-Bevacizumab Renal Impairment Drug Atezolizumab Creatinine Clearance (ml/min) N/A Dose No dose adjustment needed Bevacizumab N/A No information available * Significant changes in GFR of more than 10% may require dose adjustment. Other Dose reductions or interruptions in therapy are not necessary for those toxicities that are considered unlikely to be serious or life threatening. For example, alopecia, altered taste or nail changes. Atezolizumab Atezolizumab belongs to the immunotherapy class of cancer treatments. Autoimmune toxicities are most frequently noted and can be life threatening. If autoimmune toxicities occur delaying treatment should be considered while investigations or treatments are organised. Some, but not all, toxicities mandate cessation of treatment. Please seek guidance from relevant site- specific specialist teams or oncologists with experience of prescribing these agents. Clinicians should be aware that the current funding approval precludes further treatment after an interruption of 12 weeks or longer; this situation may change. Refer to the latest version of the European Society of Medical Oncology guidelines; Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up(3). Dose reductions or interruptions in therapy are not necessary for those toxicities that are considered unlikely to be serious or life threatening. For example, alopecia, altered taste or nail changes. Immune-related adverse reactions, which can be severe or life-threatening, may involve the gastrointestinal, liver, skin, nervous, endocrine, or other organ systems. Most occur during treatment, however, onset month’s after the last dose has been reported. Unless an alternate aetiology has been identified, diarrhoea, increased stool frequency, bloody stool, LFT elevations, rash and endocrinopathy must be considered inflammatory and atezolizumab-related. Early diagnosis and appropriate management are essential to minimise life-threatening complications. Atezolizumab should be permanently discontinued for: any NCI-CTC grade 3 or 4 pneumonitis or hepatitis; any other life- threatening NCI-CTC grade 4 reaction (including colitis and renal impairment); any recurrence of a severe or NCI-CTC grade 3 reaction; any persistent NCI-CTC grade 2 or 3 treatment-related adverse reaction that does not recover to grade 1 or resolve within 12 weeks after the last dose. Version 1 Page 4 of 11 HCC-Atezolizumab-Bevacizumab Immune-related adverse reaction Severity Immune-related pneumonitis Grade 2 pneumonitis Treatment modification Withhold until symptoms resolve and radiographic abnormalities improve. Consider treatment with oral prednisolone 1-2mg/kg or equivalent per day Treatment may be resumed if the event improves to grade 0 or grade 1 within 12 weeks, and corticosteroids have been reduced to 10mg or less oral prednisone equivalent per day. Immune-related colitis Immune-related pancreatitis Version 1 Grade 3 or 4 pneumonitis Grade 2 or 3 diarrhoea or symptomatic colitis Permanently discontinue atezolizumab. Consider treatment with corticosteroids. Withhold the atezolizumab initially. For a grade 2 diarrhoea or colitis, if the symptoms persist for more than 5 days or recur, start treatment with 1-2mg/kg oral prednisolone or equivalent per day For a grade 3 diarrhoea or colitis treatment with intravenous corticosteroids should be started, this may be converted to oral treatment as symptoms improve. If the symptoms improve to grade 1 or less taper the corticosteroids over one month Grade 4 diarrhoea or colitis Grade 3 or 4 serum amylase or lipase levels increased (more than 2xULN) or grade 2 or 3 pancreatitis Treatment may be resumed if the event improves to grade 0 or grade 1 within 12 weeks, and corticosteroids have been reduced to 10mg or less oral prednisone equivalent per day Permanently discontinue atezolizumab. Consider treatment with corticosteroids. Withhold atezolizumab Treatment with atezolizumab may be resumed if serum amylase and lipase levels improve to grade 0 or grade 1 within 12 weeks, or symptoms of pancreatitis have resolved, and corticosteroids have been reduced to 10mg or less oral Page 5 of 11 HCC-Atezolizumab-Bevacizumab Grade 4 or any grade of recurrent pancreatitis Immune-related Symptomatic thyroid disorders Immune-related Symptomatic adrenal insufficiency Immune-related Grade 3 or 4 hyperglycaemia (fasting diabetes mellitus glucose more than 250-500mg/dL) Immune-related All grades myasthenic syndrome / myasthenia gravis, Guillain-Barre syndrome and meningoencephalitis Myositis Grade 2-3 Grade 3-4 prednisone or equivalent per day Permanently discontinue atezolizumab. Consider treatment with corticosteroids. Withhold atezolizumab Hypothyroidism Treatment may be resumed when symptoms are controlled by thyroid replacement therapy and TSH levels are decreasing Hyperthyroidism Treatment may be resumed when symptoms are controlled by cabimazole or equivalent and thyroid function is improving Withhold atezolizumab Treatment may be resumed if the symptoms improve to grade 0 or grade 1 within 12 weeks and corticosteroids have been reduced to the equivalent of 10mg or less of oral prednisone or equivalent per day and patient is stable on replacement therapy Withhold atezolizumab Treatment may be resumed if metabolic control is achieved on insulin replacement therapy Permanently discontinue atezolizumab Withhold for a moderate to severe myositis and discontinue Permanently discontinue Version 1 Page 6 of 11 HCC-Atezolizumab-Bevacizumab Infusion related reactions Grade 1 Reduce the infusion rate to half Once the event has resolved, wait for 30minutes while delivering the infusion at the reduced rate. If tolerated, the infusion rate may then be increased to original rate. Consider premedication with antihistamine and antipyretic. Grade 2 Withhold atezolizumab Restart at half of the infusion rate only after the symptoms have resolved. Consider premedication with antihistamine and antipyretic. Grade 3 or 4 Permanently discontinue atezolizumab Immune-related rash Grade 3 rash or suspected StevensJohnson syndrome (SJS) or toxic epidermal necrolysis (TEN) Withhold atezolizumab Treatment may be resumed if the rash is resolved and corticosteroids have been reduced to 10mg or less oral prednisone equivalent per day Grade 4 rash or confirmed StevensJohnsons Syndrome (SJS) or toxic epidermal necrolysis (TEN) Permanently discontinue atezolizumab. Consider treatment with corticosteroids Bleeding risk Patients treated with Bevacizumab have an increased risk of haemorrhage. Cases of severe gastrointestinal haemorrhage, including fatal events, have been reported in patients with hepatocellular carcinoma treated with atezolizumab and bevacizumab. In patients with HCC, screening for and subsequent treatment of oesophageal varices should be performed as per clinical practice prior to starting treatment with the combination of atezolizumab and bevacizumab. Bevacizumab should be permanently discontinued in patients who experience grade 3 or 4 bleeding with the combination treatment. Bevacizumab Bevacizumab doses should be omitted and not reduced for adverse reactions. If more than two doses are missed due to adverse events treatment should be stopped. It should be noted that the half- life of bevacizumab is approximately twenty days. Discontinuation of treatment in response to adverse effects is not expected to influence the short- term clinical evolution of the event, symptomatic treatment is often necessary. Version 1 Page 7 of 11 HCC-Atezolizumab-Bevacizumab Bevacizumab should be stopped if the individual develops;  Gastrointestinal perforation  Arterial thromboembolic events  NCI-CTC grade 3 and above haemorrhagic events (requiring a blood transfusion or a major non-elective intervention)  NCI-CTC grade 3 and above congestive heart failure or left ventricular function  NCI-CTC grade 4 fistula If a NCI-CTC symptomatic grade 4 venous thromboembolic event occurs bevacizumab should be stopped. However, if this is a pulmonary embolism bevacizumab may be restarted once a full recovery has been made and the individual is anti-coagulated with a subcutaneous low molecular weight heparin. An oral anticoagulant must not be used. Hypertension is a common consequence of bevacizumab therapy. For a NCI-CTC grade 1 hypertension no treatment is necessary. NCI-CTC grade 2 hypertension, consider antihypertensive therapy. For a NCI-CTC grade 3 and above hypertension that is persistent consider stopping treatment. Bevacizumab may be continued for a NCI-CTC grade 1 proteinuria or the first occurrence of a grade 2 proteinuria. For the second occurrence of a NCI-CTC grade 2 proteinuria or any NCI-CTC grade 3 proteinuria give the bevacizumab as scheduled. A 24 hour urine collection or UPCR should be conducted at most three days before the next dose. If there is less than 2g protein per 24 hours or a UPCR 0-1 administer the bevacizumab and return to dipstick monitoring. If there is more than 2g protein per 24 hours omit the bevacizumab. Repeat the 24 hour urine collection prior to the next scheduled dose. If this is less than 2g per 24 hours administer the bevacizumab and continue 24 hour urine collection until the protein is 1g per 24 hours or less. Grade 4 proteinuria (nephrotic syndrome) was seen in up to 1.4% of patients treated with bevacizumab. Therapy should be permanently discontinued in patients who develop nephrotic syndrome (NCI-CTCAE v.3). Regimen 21 day cycle until disease progression or unmanageable toxicity Drug Atezolizumab Bevacizumab Dose 1200mg 15mg/kg Days 1 1 Administration Intravenous infusion in 250ml sodium chloride 0.9% over 60 minutes Intravenous infusion in 100ml sodium chloride 0.9% over 90 minutes (see administration information) Dose Information  Bevacizumab will be dose banded in accordance with the national dose bands (bevacizumab). Version 1 Page 8 of 11 HCC-Atezolizumab-Bevacizumab Administration Information Extravasation  Atezolizumab – neutral  Bevacizumab – neutral Other  The first infusion of atezolizumab should be administered over 60 minutes. If this is well tolerated subsequent infusions can be administered over 30minutes.  The first infusion of bevacizumab will be over 90 minutes. If this is well tolerated the second infusion may be given over 60 minutes. If this is well tolerated subsequent infusions may be given over 30 minutes Additional Therapy  As required for the treatment of infusion related reactions; - chlorphenamine 10mg intravenous - hydrocortisone 100mg intravenous - paracetamol 1000mg oral Additional Information  The use of systemic corticosteroids, before starting treatment with atezolizumab should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of the agent. However, systemic corticosteroids can be used after starting atezolizumab to treat immune-related adverse reactions. The use of systemic corticosteroids after starting treatment does not appear to impair the efficacy of atezolizumab.  Patients must be given an atezolizumab Patient Alert Card. References 1. Zentiva. Alymsys® Summary of product Characteristics. Updated 10/08/2021. Accessed 20/06/2022 via http://www.medicines.org.uk/emc. 2. Roche. Tecentriq® Summary of Product Characteristics. Updated 27/01/2022. Accessed 20/06/2022 via http://www.medicines.org.uk/emc. 3. Finn R S et al. Atezolizumab plus Bevacizumab in unresectable hepatocellular carcinoma. New England Journal of Medicine. 2020 May 4; 382 (20): 1894-1905. 4. Haanen J, Carbonnel F, Robert C, Kerr K.M , Peters S, Larkin J, Jordan J on behalf of the ESMO Guidelines Committee. Management of toxicities from immunotherapy. ESMO clinical practice guidelines for diagnosis, treatment and follow up. Ann Oncol 2017; 28 (suppl 4): 119-142. Version 1 Page 9 of 11 HCC-Atezolizumab-Bevacizumab REGIMEN SUMMARY Atezolizumab-Bevacizumab 1. Atezolizumab 1200mg intravenous infusion in 250ml sodium chloride 0.9% over 60 minutes Administration Instructions The first infusion of atezolizumab should be administered over 60 minutes. If this is well tolerated subsequent infusions can be administered over 30minutes. Ensure the patient has been an atezolizumab patient alert card. 2. Bevacizumab 15mg/kg intravenous infusion in 100ml sodium chloride 0.9% over 90 minutes Administration Instructions The first infusion of bevacizumab will be over 90 minutes. If this is well tolerated the second infusion may be given over 60 minutes. If this is well tolerated subsequent infusions may be given over 30 minutes 3. Chlorphenamine 10mg intravenous injection when required for infusion related reactions 4. Hydrocortisone 100mg intravenous injection when required for infusion related reactions 5. Paracetamol 1000mg oral when required for infusion related reactions Administration Instructions Please check if the patient has taken paracetamol. Maximum dose is 4g per 24 hours. There should be 4 hours between doses. Version 1 Page 10 of 11 HCC-Atezolizumab-Bevacizumab Version Date 1 June 2022 DOCUMENT CONTROL Amendment Written By Alexandra Pritchard Pharmacist Approved By Prof Tim Iveson Consultant Medical Oncologist This chemotherapy protocol has been developed as part of the chemotherapy electronic prescribing project. This was and remains a collaborative project that originated from the former CSCCN. These documents have been approved on behalf of the following Trusts; Hampshire Hospitals NHS Foundation Trust NHS Isle of Wight Portsmouth Hospitals NHS Trust Salisbury NHS Foundation Trust University Hospital Southampton NHS Foundation Trust Western Sussex Hospitals NHS Foundation Trust All actions have been taken to ensure these protocols are correct. However, no responsibility can be taken for errors which occur as a result of following these guidelines. Version 1 Page 11 of 11 HCC-Atezolizumab-Bevacizumab
Url
/Media/UHS-website-2019/Docs/Chemotherapy-SOPs1/Hepatobiliary/Atezolizumab-Bevacizumab.pdf

Press release: Pioneering one-stop cancer clinic up for prestigious national award

Description
A pioneering one-stop clinic developed by clinicians in Southampton which speeds up access to pain relief and support for cancer patients has been recognised nationally for its success.
Url
/AboutTheTrust/Newsandpublications/Latestnews/2018/September-2018/Press-release-Pioneering-one-stop-cancer-clinic-up-for-prestigious-national-award.aspx

Researchers to address "mismatch" in care for patients with neurological conditions

Description
Researchers in Southampton are leading a study into the needs of patients with long-term neurological conditions to address a "mismatch" with the clinical and social care services they require at different stages of their illness.
Url
/AboutTheTrust/Newsandpublications/Latestnews/2018/February-2018/Researchers-to-address-mismatch-in-care-for-patients-with-neurological-conditions.aspx

Southampton doctors implant coin-sized heart failure monitor

Description
Cardiac experts in Southampton have fitted a heart failure patient with a revolutionary monitoring device the size of a 5p coin.
Url
/AboutTheTrust/Newsandpublications/Latestnews/2017/March-2017/Southampton-doctors-implant-coin-sized-heart-failure-monitor.aspx

What to expect in the last days and weeks of life: When your loved one has been discharged from hospital - patient information

Description
This booklet provides information for family, friends and carers who will be supporting a loved one during their last days and weeks after they are discharged from hospital.
Url
/Media/UHS-website-2019/Patientinformation/Bereavement-and-end-of-life/What-to-expect-in-the-last-days-and-weeks-of-life-When-your-loved-one-has-been-discharged-from-hospital-3685-PIL.pdf
1 to 10 of 230
Previous 1 2 3 4 5 … Next