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Urinary tract infection - patient information

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Patient information factsheet Urinary tract infections (UTIs) Urinary tract infections (UTIs) are very common. They can be painful and uncomfortable, but
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Capecitabine-Epirubicin-Oxaliplatin (EOX)

Description
Chemotherapy Protocol GASTROINTESTINAL (UPPER) CANCER CAPECITABINE, EPIRUBICIN and OXALIPLATIN (EOX) Regimen • Gastrointestinal Cancer (upper) – Capecitabine-Epirubicin-Oxaliplatin (EOX) Indication • First line
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Capecitabine-Oxaliplatin 4-cycles

Description
Chemotherapy Protocol COLORECTAL CANCER CAPECITABINE and OXALIPLATIN (CAPOX-4 cycles) Regimen • Colorectal Cancer – Capecitabine-Oxaliplatin 4 cycles (CAPOX-4 cycles) Indication
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Capecitabine-Oxaliplatin

Description
Chemotherapy Protocol COLORECTAL CANCER CAPECITABINE and OXALIPLATIN (CAPOX) Regimen • Colorectal Cancer – Capecitabine-Oxaliplatin (CAPOX) Indication • Advanced / metastatic colorectal cancer • Adjuvant therapy
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/Media/UHS-website-2019/Docs/Chemotherapy-SOPs1/Colorectal/Capecitabine-Oxaliplatin.pdf

Fulvestrant-Ribociclib

Description
Chemotherapy Protocol Breast Cancer Fulvestrant-Ribociclib Regimen • Breast Cancer – Fulvestrant-Ribociclib Indication • Fulvestrant and ribociclib is indicated for oestrogen receptor-positive
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Bevacizumab-Capecitabine-Oxaliplatin

Description
Chemotherapy Protocol COLORECTAL CANCER BEVACIZUMAB-CAPECITABINE-OXALIPLATIN This protocol may require funding Regimen • Colorectal Cancer– Bevacizumab-Capecitabine-Oxaliplatin Indication • Metastatic colorectal cancer • WHO performance status 0, 1 Toxicity Drug Bevacizumab Capecitabine Oxaliplatin Adverse Effect Haemorrhage, hypertension, proteinuria, impaired wound healing, gastrointestinal perforations, fistulae, arterial thrombosis Palmar-plantar erythrodysesthesia, diarrhoea, mucositis, chest pain Peripheral neuropathy (cumulative), acute laryngopharyngeal dysasthesia (increase duration of infusion) 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 one of treatment • Blood pressure and dipstick urinalysis for proteinuria prior to treatment with bevacizumab • Patients with complete or partial dihydropyrimidine dehydrogenase (DPD) deficiency are at increased risk of severe and fatal toxicity during treatment with capecitabine. All patients should be tested for DPD deficiency before initiation (cycle 1) to minimise the risk of these reactions. Dose Modifications The dose modifications listed are for haematological, liver and renal function and some drug specific toxicities only. Dose adjustments may be necessary for other toxicities as well. Version 1.2 (November 2020) Page 1 of 9 Colorectal-Bevacizumab-Capecitabine-Oxaliplatin 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. The following is a general guide only. Haematological Consider blood transfusion if patient symptomatic of anaemia or has a haemoglobin of less than 8g/dL. (See below for information on bevacizumab and transfusions). Prior to prescribing on day one of cycle one the following criteria must be met; Criteria Neutrophils Platelets Eligible Level Equal to or more than 1.5x109/L Equal to or more than 100x109/L Dose modifications for haematological toxicity apply to capecitabine and oxaliplatin only. Neutrophils (x109/L) 1.5 or greater less than 1.5 Platelets (x109/L) 75 or greater less than 75 Dose Modifications (capecitabine and oxaliplatin) 100% Delay until neutrophils recover to 1.5x109/L or greater. If recovery occurs within 7 days restart at 100% of the original dose. If recovery occurs within 7-14 days restart at 75% (100% where appropriate) of the original dose. If recovery takes greater than 21 days stop treatment. Dose Modifications (capecitabine and oxaliplatin) 100% Delay until platelets recover to 75x109/L or greater. If recovery occurs within 7 days restart at 100% of the original dose. If recovery occurs within 7-14 days restart at 75% (100% where appropriate) of the original dose. If recovery takes greater than 21 days stop treatment. There is little need to adjust the dose of bevacizumab for haematological toxicity. Version 1.2 (November 2020) Page 2 of 9 Colorectal-Bevacizumab-Capecitabine-Oxaliplatin Hepatic Impairment Please note that the approach may be different where abnormal liver function tests are due to disease involvement. Drug Bevacizumab Bilirubin (μmol/L) n/a AST/ALT Dose (% of original dose) n/a No information available Capecitabine greater than 3xULN If treatment related consider or greater than 2.5xULN delaying treatment. For mild/moderate hepatic dysfunction due to liver metastasis dose modification may not be necessary. Oxaliplatin n/a n/a No dose adjustment necessary Renal Impairment Drug Bevacizumab Creatinine Clearance (ml/min) n/a Dose (% of original dose) No information available Capecitabine 51 or greater 30-50 less than 30 100% 75% Contra-indicated Oxaliplatin 30 or greater less than 30 Dose adjust according to toxicity Avoid 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. 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. Bevacizumab should be stopped if the individual develops; Version 1.2 (November 2020) Page 3 of 9 Colorectal-Bevacizumab-Capecitabine-Oxaliplatin • 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. Capecitabine NCI-CTC Grade 2 Interrupt treatment until the toxicity resolves to NCI-CTC grade 0-1 then continue at the same dose. If the toxicity recurs for a second time again interrupt treatment until it resolves to NCI-CTC grade 0-1 then resume therapy at 75% of the original dose. If the same adverse effect develops on a third occasion once more interrupt treatment until it resolves to grade 01 then continue at 50% of the original dose. Stop treatment if the toxicity re-appears on a fourth instance. NCI-CTC Grade 3 Interrupt treatment until the toxicity resolves to NCI-CTC grade 0-1 then continue treatment using 75% of the original dose with prophylaxis if appropriate. If the toxicity recurs for a second time again interrupt treatment until it resolves to NCI-CTC grade 0-1 and then resume therapy at 50% of the original dose. If the same adverse effect develops on a third occasion discontinue capecitabine. NCI-CTC Grade 4 Discontinue treatment unless the responsible consultant considers it to be in the best interest of the patient to continue at 50% of the original dose once the toxicity has resolved to NCI-CTC grade 0-1. When capecitabine is stopped for toxicity the doses are omitted, not delayed. Version 1.2 (November 2020) Page 4 of 9 Colorectal-Bevacizumab-Capecitabine-Oxaliplatin Oxaliplatin For cold related dysaesthesia or paresthesia without pain there is no need to dose delay or reduce unless it persists between cycles. In this instance withhold the oxaliplatin until recovery and then re-start treatment using 100mg/m2. Only omit the oxaliplatin if it recurs. For paresthesiae with pain or functional impairment that lasts 7 days or less no dose modification is necessary. If it persists beyond 7 days or is NCI-CTC grade 3 and above, in the first instance reduce the dose to 100mg/m2. If the painful paresthesia recurs or persists between cycles omit the oxaliplatin. If NCI-CTC grade 3-4 diarrhoea or stomatitis recurs despite appropriate reduction in the capecitabine dose the oxaliplatin dose should be reduced to 100mg/m2. There are rare case reports of acute interstitial lung disease or lung fibrosis in association with oxaliplatin. Where an unexplained respiratory symptom occurs stop treatment until pulmonary investigations have been conducted to exclude an interstitial cause. Regimen 21 day cycle for 6 cycles Drug Bevacizumab Capecitabine Oxaliplatin Dose 7.5mg/kg 1000mg/m2 twice a day 130mg/m2 Days 1 1-14 1 Administration Intravenous infusion in 100ml sodium chloride 0.9% over 90 minutes (see administration information) Oral Intravenous infusion in 500ml glucose 5% over 120 minutes If continuing treatment beyond six cycles consider stopping oxaliplatin from cycle 7 onwards to minimise the risk of serious peripheral sensory neuropathy. If oxaliplatin is stopped the dose of capecitabine may be increased at this point to 1250mg/m2 twice a day if clinically appropriate. Dose Information • Bevacizumab will be dose banded in accordance with the national dose bands (25mg/ml NS) • In patients over 70 years old consider initiating capecitabine treatment at 800mg/m2 twice a day. • Capecitabine will be dose banded in accordance with the national dose bands • Oxaliplatin will be dose banded in accordance with the national dose bands (5mg/ml) Version 1.2 (November 2020) Page 5 of 9 Colorectal-Bevacizumab-Capecitabine-Oxaliplatin Administration Information Extravasation • Bevacizumab - neutral • Oxaliplatin - exfoliant Other • 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 • Capecitabine should start on the evening of day 1 • Capecitabine should be taken with or after food • A glucose 5% flush should be administered before and after the oxaliplatin Additional Therapy • Antiemetics 15-30 minutes prior to chemotherapy - ondansetron 8mg oral or intravenous - dexamethasone 8mg oral or equivalent intravenous dose As take home medication - dexamethasone 4mg oral twice a day for 3 days - metoclopramide 10mg oral three times a day for 3 days then when required • Oral loperamide 4mg initially then 2mg after each loose stool when required for the relief of diarrhoea (maximum 16mg/24 hours). • Mouthcare for the prophylaxis or treatment of mucositis in accordance with local or national guidelines • 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. Additional Information • The National Patient Safety Agency alert NPSA/2008/RRR001 must be followed when prescribing, dispensing or administering oral chemotherapy. • Ensure the total daily dose of capecitabine is divided into two doses given twelve hours apart (the first should be administered in the evening of day one of the cycle). Version 1.2 (November 2020) Page 6 of 9 Colorectal-Bevacizumab-Capecitabine-Oxaliplatin Serious toxicity has occurred where the total daily dose has been given twice a day. • It must be made clear to all staff, including those in the community, that this is a short course of oral chemotherapy that must not be continued. References 1. Diaz-Rubio E, Gomez-Espana A, Massuti B et al. First line XELOX plus bevacizumab followed by XELOX plus bevacizumab or single agent bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: The phase III MACRO TTD study. The Oncologist 2012; 17 (1): 15-25. Version 1.2 (November 2020) Page 7 of 9 Colorectal-Bevacizumab-Capecitabine-Oxaliplatin REGIMEN SUMMARY Bevacizumab-Capecitabine-Oxaliplatin Day 1 1. Dexamethasone 8mg oral or intravenous 2. Ondansetron 8mg oral or intravenous 3. Bevacizumab 7.5mg/kg intravenous infusion in 100ml sodium chloride 0.9% over 90 minutes 4. Oxaliplatin 130mg/m2 intravenous infusion in 500ml glucose 5% over 120 minutes Take home medicines 5. Capecitabine 1000mg/m2 oral twice a day for 14 days starting on the evening of day one of the cycle 6. Dexamethasone 4mg oral twice a day for 3 days starting the day after chemotherapy administration 7. Metoclopramide 10mg oral three times a day for 3 days then when required for the relief of nausea. Version 1.2 (November 2020) Page 8 of 9 Colorectal-Bevacizumab-Capecitabine-Oxaliplatin DOCUMENT CONTROL Version Date Amendment Written By Approved By Updated monitoring with DPD testing 1.2 Nov 2020 Dose banding statement updated Donna Kimber Pharmacy Technician Rebecca Wills Pharmacist Coding removed Header changed < symbol removed from paragraph on dose modifications Capecitabine dose modifications for age moved to section on “dose modifications” Bolus removed from intravenous 1.1 bolus May 2014 Metoclopramide dose changed to 10mg throughout Dr Deborah Wright Pharmacist Donna Kimber Pharmacy Technician Dexamethasone and capecitabine administration clarified Coding updated Intravenous added to antiemetics in summary Disclaimer added Rebecca Wills Pharmacist Dr Tim Iveson 1 Feb 2013 None Consultant Medical Dr Deborah Wright Oncologist 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 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 1.2 (November 2020) Page 9 of 9 Colorectal-Bevacizumab-Capecitabine-Oxaliplatin
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Capecitabine-Cetuximab-Oxaliplatin

Description
Chemotherapy Protocol COLORECTAL CANCER CAPECITABINE-CETUXIMAB-OXALIPLATIN (21 day) This regimen may require funding Regimen • Colorectal Cancer – Capecitabine-Cetuximab-Oxaliplatin (21 day) Indication • Cetuximab in combination with fluoropyrimidine and oxaliplatin chemotherapy is recommended as a possible first or second line treatment for people with metastatic colorectal cancer when: - surgery to remove the cancer in the colon or rectum has been carried out or is possible - the metastases are only in the liver and cannot be removed surgically before treatment - the person is fit enough to have surgery to remove the cancer in the colon or rectum and to have liver surgery if it becomes possible to remove the metastases after cetuximab treatment • The tumour is positive for the wild type KRAS genotype • WHO performance status 0, 1, 2 Toxicity Drug Capecitabine Cetuximab Oxaliplatin Adverse Effect Palmar-plantar erythrodysesthesia, diarrhoea, mucositis, chest pain Infusion related reactions, interstitial lung disease, skin reactions, electrolyte abnormalities, fatigue, abdominal pain, constipation Peripheral neuropathy (cumulative), acute laryngopharyngeal dysasthesia (increase duration of infusion) The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Monitoring Regimen Version 1.3 (October 2020) Page 1 of 12 Colorectal – Capecitabine-Cetuximab-Oxaliplatin (21 day) • Prior to starting therapy confirm a positive KRAS status • FBC, LFT’s and U&E’s prior to day one of treatment • Monitor for hypersensitivity reactions for 60 minutes after the end of the cetuximab infusion • Patients with complete or partial dihydropyrimidine dehydrogenase (DPD) deficiency are at increased risk of severe and fatal toxicity during treatment with capecitabine. All patients should be tested for DPD deficiency before initiation (cycle 1) to minimise the risk of these reactions 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. The following is a general guide only. Haematological Prior to prescribing the following criteria must be met. Criteria Neutrophil Platelets Eligible Level equal to or more than 1.5x109/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 For haematological toxicity, if the neutrophil count is less than 1.5 109/L or the platelet count is less than 75 109/L, delay treatment until these levels are achieved. Re-initiate therapy at the full dose for a seven day delay or with 75% of the original dose for a fourteen day delay (consider re-starting with 100%). If the delay is more than 20 days stop therapy. There is little need to adjust the dose of cetuximab for haematological toxicity. Hepatic / Renal Impairment Deteriorating liver or kidney function may be a sign of disease progression or drug toxicity. Version 1.3 (October 2020) Page 2 of 12 Colorectal – Capecitabine-Cetuximab-Oxaliplatin (21 day) Hepatic Impairment Drug Capecitabine Cetuximab Oxaliplatin Dose (% of original dose) There is little published information available. No dose reductions are necessary for those with mild to moderate hepatic dysfunction due to liver metastasis Administer only when the transaminases are 5xULN or below and the bilirubin is 1.5xULN or below There is little published information available. No dose reductions are probably necessary. Renal Impairment Drug Capecitabine Cetuximab Creatinine Clearance (ml/min) Dose (% of original dose) More than 51 30-50 less than 30 more than 180 (1.5xULN) 100 75 Do not use Do not use Oxaliplatin Less than 20 Dose reduce and adjust according to toxicity 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. Dose limiting toxicities include diarrhoea, abdominal pain, emesis, stomatitis, palmar-plantar erythrodysesthesia and neurosensory toxicities among others. If any NCI-CTC grade 1 toxicity occurs treatment should be continued, without interruption, at the full dose. For toxicities NCI-CTC grade 3 or above in general treatment should be withheld until recovery to at least NCI-CTC grade 1 then re-started if medically appropriate. If recovery takes twenty-one days or longer then stop treatment. Capecitabine NCI-CTC Grade 2 Interrupt treatment until the toxicity resolves to NCI-CTC grade 0-1 then continue at the same dose. If the toxicity recurs for a second time again interrupt treatment until it resolves to NCI-CTC grade 0-1 then resume therapy at 75% of the original dose. If the same adverse effect develops on a third occasion once more interrupt treatment until it resolves to NCI-CTC grade 0-1 then continue at 50% of the original dose. Stop treatment if the toxicity re-appears on a fourth instance. Version 1.3 (October 2020) Page 3 of 12 Colorectal – Capecitabine-Cetuximab-Oxaliplatin (21 day) NCI-CTC Grade 3 Interrupt treatment until the toxicity resolves to NCI-CTC grade 0-1 then continue treatment using 75% of the original dose with prophylaxis if appropriate. If the toxicity recurs for a second time again interrupt treatment until it resolves to NCI-CTC grade 0-1 and then resume therapy at 50% of the original dose. If the same adverse effect develops on a third occasion discontinue capecitabine. NCI-CTC Grade 4 Discontinue treatment unless the responsible consultant considers it to be in the best interest of the patient to continue at 50% of the original dose once the toxicity has resolved to NCI-CTC grade 0-1. When capecitabine is stopped for toxicity the doses are omitted, not delayed. Consider stopping capecitabine therapy if chest pain occurs. Cetuximab Allergic or hypersensitivity reactions have occurred during the administration of cetuximab. For a NCI-CTC grade 1 reaction reduce the infusion rate by 50%. For a NCI-CTC grade 2 reaction, stop the infusion and administer supportive therapies as indicated. Once the reaction has resolved to NCI-CTC grade 1 or below resume the infusion at 50% of the previous rate. For a NCI-CTC grade 3 or 4 toxicity stop the infusion immediately and disconnect the tubing from the patient. Administer appropriate supportive therapies. Once recovered, patients should not receive cetuximab again. Once the rate has been reduced it should not be increased on subsequent infusions. If a second reaction occurs on the slower infusion rate the infusion should be stopped and no further treatment given. An acniform skin rash occurs in over 70% of those receiving cetuximab. The onset is normally within three weeks of starting therapy and often resolves after week twelve. For a NCI-CTC grade 1-2 reaction use symptomatic treatments such as topical or oral antibiotics and continue with the cetuximab. For a NCI-CTC grade 3 toxicity delay treatment until the toxicity resolves to NCI-CTC grade 2 or below. If this occurs within fourteen days resume cetuximab at the same dose. If more than fourteen days is required stop treatment. If the NCI-CTC grade 3 toxicity occurs for a second and third time the cetuximab may again be delayed for up to and including fourteen days with concomitant dose reductions to 200mg/m2 and 150mg/m2 respectively. Cetuximab dose reductions are permanent. The cetuximab must be discontinued if more than two consecutive infusions are withheld or a fourth episode of a NCI-CTC grade 3 skin toxicity develops or a NCI-CTC grade 4 toxicity at any time. UV radiation may worsen skin reactions. Sun safety practices should be followed during and for up to two months after the end of treatment. Stop treatment if there is a confirmed pneumonitis. Version 1.3 (October 2020) Page 4 of 12 Colorectal – Capecitabine-Cetuximab-Oxaliplatin (21 day) Oxaliplatin For cold related dysaesthesia or paresthesia without pain there is no need to dose delay or reduce unless it persists between cycles. In this instance withhold the oxaliplatin until recovery and then re-start treatment using 100mg/m2. Only omit the oxaliplatin if it recurs. For paresthesia with pain or functional impairment that lasts up to seven days no dose modification is necessary. If it persists beyond seven days or is NCI-CTC grade 3 and above, in the first instance reduce the dose to 100mg/m2. If the painful paresthesia recurs or persists between cycles omit the oxaliplatin. If NCI-CTC grade 3-4 diarrhoea or stomatitis recurs despite appropriate reduction in the capecitabine dose the oxaliplatin dose should be reduced to 100mg/m2. There are rare case reports of acute interstitial lung disease or lung fibrosis in association with oxaliplatin. Where an unexplained respiratory symptom occurs stop treatment until pulmonary investigations have been conducted to exclude an interstitial cause. Regimen 21 day cycle for 6 cycles Cycle One Drug Capecitabine Cetuximab Cetuximab Oxaliplatin Dose 800mg/m2 twice a day 400mg/m2 250mg/m2 130mg/m2 Days Route 1-14 incl Oral 1 8, 15 1 Intravenous infusion (see administration) Intravenous infusion (see administration) Intravenous infusion in 500ml glucose 5% over 120 minutes Cycle Two Onwards Drug Dose Capecitabine 800mg/m2 twice a day Cetuximab 250mg/m2 Oxaliplatin 130mg/m2 Days 1-14 incl 1, 8, 15 1 Route Oral Intravenous infusion (see administration) Intravenous infusion in 500ml glucose 5% over 120 minutes Dose Information • Capecitabine will be dose banded in accordance with the national dose bands • Cetuximab will be dose banded in accordance with the national dose bands (5mg/ml) Version 1.3 (October 2020) Page 5 of 12 Colorectal – Capecitabine-Cetuximab-Oxaliplatin (21 day) • Oxaliplatin will be dose banded in accordance with the national dose bands (5mg/ml) Administration Information Extravasation • Cetuximab - neutral • Oxaliplatin – exfoliant Other • Capecitabine should start on the evening of day 1 • Capecitabine should be taken with or after food • Individuals should be monitored for hypersensitivity reactions for sixty minutes after finishing the cetuximab infusion. Do not administer other chemotherapy during this period. • The rate of administration of cetuximab must not exceed 5mg/min for the first infusion (minimum 120 minutes). If well tolerated subsequent infusions may be given at a rate of 10mg/min (minimum 60 minutes). • Oxaliplatin must never come into contact with sodium chloride 0.9%. Ensure the line is flushed with glucose 5% before and after each oxaliplatin infusion Additional Therapy • Antiemetics 15-30 minutes prior to chemotherapy on day one only; - dexamethasone 8mg oral or intravenous - ondansetron 8mg oral or intravenous As take home medication; - dexamethasone 4mg twice a day oral for 3 days - metoclopramide 10mg three times a day when required oral • 30 minutes prior to cetuximab infusion; - chlorphenamine 10mg intravenous - dexamethasone 8mg oral or intravenous (given as part of antiemetic regimen on day 1) - H2 antagonist according to local formulary choice and availability - paracetamol 1000mg oral Version 1.3 (October 2020) Page 6 of 12 Colorectal – Capecitabine-Cetuximab-Oxaliplatin (21 day) • Oral loperamide 4mg after the first loose stool then 2-4mg four times a day when required for the relief of diarrhoea (maximum 16mg/24 hours). • Mouthwashes according to local or national policy on the treatment of mucositis • 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 Additional Information • The National Patient Safety Agency alert NPSA/2008/RRR001 must be followed when prescribing, dispensing or administering oral chemotherapy. • Ensure the total daily dose of capecitabine is divided into two doses given twelve hours apart (the first should be administered in the evening of day one of the cycle) Serious toxicity has occurred where the total daily dose has been given twice a day. • It must be made clear to all staff, including those in the community, that this is a short course of oral chemotherapy that must not be continued. References 1. Moosnann N, von Weikersthal LF, Vehling-Kaiser U et al. Cetuximab plus capecitabine and irinotecan compared with cetuximab plus capecitabine and oxaliplatin as first line treatment for patients with metastatic colorectal cancer. AIO KRK-0104 – a randomised trial of the German AIO CRC study group. JCO 2011; 29 (8): 1050-1058. 2. Maughan TS, Adams RS, Smith CG et al. Addition of cetuximab to oxaliplatin based first line combination chemotherapy for the treatment of advanced colorectal cancer; results of the randomised phase III MRC COIN trial. Lancet 2011; 377 (9783); 2103-2114. Version 1.3 (October 2020) Page 7 of 12 Colorectal – Capecitabine-Cetuximab-Oxaliplatin (21 day) REGIMEN SUMMARY Capecitabine-Cetuximab-Oxaliplatin (21 day) Day One Cycle One 1. Chlorphenamine 10mg intravenous 2. Dexamethasone 8mg oral or intravenous 3. Paracetamol 1000mg oral Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg in every 24 hours 4. H2 antagonist according to local formulary choice and availability Administration Instructions: Administer according to local formulary choice and availability one of the following 30 minutes prior to chemotherapy; - Ranitidine 50mg intravenous once only - Famotidine 20mg oral once only - Nizatidine 150mg oral once only - Ranitidine 150mg oral once only If there is no stock of these products due to national shortages treatment may proceed without the H2 antagonist provided there is no instruction in the ARIA journal indication the patient must have H2 antagonist treatment. All infusion related reactions must be recorded in the ARIA journal and reported to the appropriate consultant. Many Trusts do not administer an H2 antagonist from cycle three onwards. They have been left in the ARIA protocols so that decisions can be made on an individual Trust and patient basis. 5. Cetuximab 400mg/m2 intravenous infusion An interval of 60 minutes should be left between administration of cetuximab and oxaliplatin 6. Ondansetron 8mg oral or intravenous 7. Oxaliplatin 130mg/m2 intravenous infusion in 500ml glucose 5% over 120 minutes Take Home Medicines 8. Capecitabine 800mg/m2 twice a day for 14 days oral 9. Dexamethasone 4mg twice a day for 3 days oral starting the day after oxaliplatin 10. Metoclopramide 10mg three times a day when required oral Day Eight and Fifteen Cycle One 1. Chlorphenamine 10mg intravenous 2. Dexamethasone 8mg oral or intravenous 3. Paracetamol 1000mg oral Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg in every 24 hours Version 1.3 (October 2020) Page 8 of 12 Colorectal – Capecitabine-Cetuximab-Oxaliplatin (21 day) 4. H2 antagonist according to local formulary choice and availability Administration Instructions: Administer according to local formulary choice and availability one of the following 30 minutes prior to chemotherapy; - Ranitidine 50mg intravenous once only - Famotidine 20mg oral once only - Nizatidine 150mg oral once only - Ranitidine 150mg oral once only If there is no stock of these products due to national shortages treatment may proceed without the H2 antagonist provided there is no instruction in the ARIA journal indication the patient must have H2 antagonist treatment. All infusion related reactions must be recorded in the ARIA journal and reported to the appropriate consultant. Many Trusts do not administer an H2 antagonist from cycle three onwards. They have been left in the ARIA protocols so that decisions can be made on an individual Trust and patient basis. 5. Cetuximab 250mg/m2 intravenous infusion Day One Cycle Two Onwards 1. Chlorphenamine 10mg intravenous 2. Dexamethasone 8mg oral or intravenous 3. Paracetamol 1000mg oral Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg in every 24 hours 4. H2 antagonist according to local formulary choice and availability Administration Instructions: Administer according to local formulary choice and availability one of the following 30 minutes prior to chemotherapy; - Ranitidine 50mg intravenous once only - Famotidine 20mg oral once only - Nizatidine 150mg oral once only - Ranitidine 150mg oral once only If there is no stock of these products due to national shortages treatment may proceed without the H2 antagonist provided there is no instruction in the ARIA journal indication the patient must have H2 antagonist treatment. All infusion related reactions must be recorded in the ARIA journal and reported to the appropriate consultant. Many Trusts do not administer an H2 antagonist from cycle three onwards. They have been left in the ARIA protocols so that decisions can be made on an individual Trust and patient basis. 5. Cetuximab 250mg/m2 intravenous infusion 6. Ondansetron 8mg oral or intravenous 7. Oxaliplatin 130mg/m2 intravenous infusion in 500ml glucose 5% over 120 minutes Take Home Medicines 8. Capecitabine 800mg/m2 twice a day for 14 days oral 9. Dexamethasone 4mg twice a day for 3 days oral starting the day after oxaliplatin 10. Metoclopramide 10mg three times a day when required oral Version 1.3 (October 2020) Page 9 of 12 Colorectal – Capecitabine-Cetuximab-Oxaliplatin (21 day) Day Eight and Fifteen Cycle Two Onwards 1. Chlorphenamine 10mg intravenous 2. Dexamethasone 8mg oral or intravenous 3. Paracetamol 1000mg oral Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg in every 24 hours 4. H2 antagonist according to local formulary choice and availability Administration Instructions: Administer according to local formulary choice and availability one of the following 30 minutes prior to chemotherapy; - Ranitidine 50mg intravenous once only - Famotidine 20mg oral once only - Nizatidine 150mg oral once only - Ranitidine 150mg oral once only If there is no stock of these products due to national shortages treatment may proceed without the H2 antagonist provided there is no instruction in the ARIA journal indication the patient must have H2 antagonist treatment. All infusion related reactions must be recorded in the ARIA journal and reported to the appropriate consultant. Many Trusts do not administer an H2 antagonist from cycle three onwards. They have been left in the ARIA protocols so that decisions can be made on an individual Trust and patient basis. 5. Cetuximab 250mg/m2 intravenous infusion Version 1.3 (October 2020) Page 10 of 12 Colorectal – Capecitabine-Cetuximab-Oxaliplatin (21 day) DOCUMENT CONTROL Version Date Amendment Written By Approved By 1.3 October Update of premedication due to Arum Shortland Dr Debbie Wright 2020 shortage of IV ranitidine. Pharmacist Pharmacist IV ranitidine changed to H2 antagonist according to local formulary choice and availability Coding removed Monitoring updated with DPD testing 1.2 May 2014 Header changed Dr Debbie Wright Donna Kimber Metoclopramide dose changed Pharmacist Pharmacy Technician to 10mg Cetuximab administration changed to reflect SPC Mucositis recommendation changed Bolus removed from supportive therapies Coding updated Disclaimer added 1.1 Nov 2011 In the “Additional Therapy” section, dexamethasone added to the cetuximab premedication Dr Debbie Wright Becky Wills with statement regarding anti- Pharmacist Pharmacist emetic on day 1. Ondansetron moved in the regimen summary to be given after the cetuximab. In the regimen summary spelling of chlorpheniramine changed to chlorphenamine Spelling mistakes in dose modifications corrected (with out to without and paresthesiae to paresthesia) 1 Sept 2011 None Dr Debbie Wright Dr Tim Iveson Pharmacist 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 Hospital NHS Foundation Trust Version 1.3 (October 2020) Page 11 of 12 Colorectal – Capecitabine-Cetuximab-Oxaliplatin (21 day) 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 1.3 (October 2020) Page 12 of 12 Colorectal – Capecitabine-Cetuximab-Oxaliplatin (21 day)
Url
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Letrozole-Ribociclib

Description
Chemotherapy Protocol Breast Cancer Letrozole-Ribociclib Regimen • Breast Cancer – Letrozole-Ribociclib Indication • Ribociclib in combination with an aromatase inhibitor is indicated for the treatment previously untreated, hormone receptor-positive, HER2- negative, locally advanced or metastatic breast cancer that is not amenable to curative treatment and where; - the patient has had no prior treatment with a CDK 4/6 inhibitor unless either palbociclib has had to be stopped within 3 months of its start solely as a consequence of dose-limiting toxicity and in the clear absence of disease progression or ribociclib has been received as part of the compassionate use scheme and the patient meets all the other criteria - the patient is male or is female and either post-menopausal or if pre- or perimenopausal has undergone ovarian ablation or suppression with LHRH agonist treatment - the patient has had no previous hormone therapy for locally advanced or metastatic disease i.e. is hormone therapy naïve for locally advanced/metastatic breast cancer. Previous hormone therapy with anastrozole or letrozole whether as adjuvant therapy or as neoadjuvant treatment is allowed as long as the patient has had a disease-free interval of 12 months or more since completing treatment with anastrazole or letrozole. - WHO performance status of 0 – 2 Toxicity Treatment breaks of up to 6 weeks are allowed for ribociclib but solely to allow toxicities to settle. Drug Letrozole Ribociclib Adverse Effect Osteoporosis, headache, somnolence, hot flushes, alopecia, arthralgia, rash, vaginal dryness, asthenia, liver abnormalities, depression, insomnia Infection, myelosuppression, peripheral neuropathy, fatigue, mucositis, anorexia, eye disorders, venous thromboembolism, cadiac abnormalities The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Version 1 (Feb 2018) 1 Breast – Letrozole-Ribociclib Monitoring Drugs • FBC, LFTs and U&Es at baseline and then on day one of each cycle (every twenty-eight days). • For cycle one and two only the FBC and LFTs should be assessed on day one and fourteen of the cycle (the full cycle of ribociclib may be dispensed on day 1) • ECG should be assessed before initiating treatment with ribociclib. After initiating treatment, ECG should be repeated at approximately day 14 of the first cycle and at the beginning of the second cycle, then as clinically indicated. In case of QTcF prolongation during treatment, more frequent ECG monitoring is recommended. 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. The following is a general guide only. Haematological Dose modifications for haematological toxicity in the table below are for general guidance only. Always refer to the responsible consultant as any dose reductions or delays will be dependent on clinical circumstances and treatment intent. 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) Prior to prescribing cycle 1 the following criteria must be met. Criteria Neutrophils Platelets Eligible Level Equal to or more than 1.0x109/L Equal to or more than 100x109/L Thereafter dose adjustments for haematological toxicity are described in the table below; Version 1 (Feb 2018) 2 Breast – Letrozole-Ribociclib Toxicity Grade Ribociclib dose Haematological 1 or 2 No change Day 1: Delay one week. When recovered to NCI-CTC grade 2 or below restart at same dose Day 14 of first 2 cycles: continue current dose to complete 3 the cycle. Repeat the FBC on day 21. Consider dose reduction if the recovery to eligible levels takes 7 days or longer or there is recurrent NCI-CTC grade 3 neutropenia in subsequent cycles 3 with Delay until recovery to NCI-CTC grade 2 or below. Restart at fever next lower dose level 4 Delay until recovery to NCI-CTC grade 2 or below. Restart at next lower dose level Neutropenia was the most frequently reported adverse effect of ribociclib with a median onset of 15 days for any grade and 28 days for NCI-CTC grade 3 or 4. Median duration of severe neutropenia was seven days and most patients had their ribociclib dose reduced or held. No dose reductions are required for letrozole due to myelosuppression. Hepatic Impairment No dose change for letrozole is recommended in patients with mild hepatic disease. Caution is advised in patients with moderate to severe hepatic impairment Ribcoclib in Hepatic Impairment NCI-CTC Grade 1 No dose adjustment NCI-CTC Grade 2 No dose adjustment NCI-CTC Grade 3 Delay treatment until recovery to NCI-CTC grade 2 or below, then resume at the same dose level.If a NCI-CTC grade 2 toxicity recurs resume traement at the lower dose level NCI-CTC Grade 4 Interupt the dose until recovery to NCI-CTC grade 2 or below then resume at the next lowest dose level. Discontinue of NCI- CTC toxicity recurs. Combination If patients develop ALT and/or AST greater than 3xULN along with total bilirubin greater than 2xULN irrespective of baseline grade, discontinue ribociclib Renal Impairment No dose change is recommended for letrozole in patients with mild or moderate renal impairment. In patients with severe renal impairment, administration of letrozole should be performed with caution No dose adjustments of ribociclib are required for patients with mild to moderate renal impairment (creatinine clearance [CrCl] more than or equal to 30ml/min). Insufficient data are available in patients with severe renal impairment (CrCl less than 30ml/min) or requiring haemodialysis to provide any dose adjustment recommendation. Administer ribociclib to patients with severe renal impairment only after careful consideration of the potential benefits and risks and with close monitoring of signs of toxicity. Version 1 (Feb 2018) 3 Breast – Letrozole-Ribociclib Other Doses for other toxicities should be adjusted according to the table below; Dose Level 0 -1 -2 Ribociclib Dose (mg/day) 600 400 200 Letrozole dose (mg/day) 2.5 2.5 2.5 Ribociclib should be discontinued if the 200mg dose is not tolerated. Ribociclib Dose Adjustments Other non- NCI-CTC Grade 1 haematologic or 2 al or cardiac No dose toxicities adjustment is required. Initiate appropriate medical therapy and monitor as clinically indicated. NCI-CTC Grade 3 NCI-CTC Grade 4 Dose interruption until recovery to NCI-CTC grade 1 or below, then resume ribociclib at the same dose level. If NCI-CTC grade 3 recurs, resume ribociclib at the next lower dose level. Discontinue ribociclib Infections were reported more frequently in the ribociclib combination treatment arm versus the single agent aromatase inhibitor alone arm and may be severe. Patients should be warned of the increased risk of infection and promptly report any occurrences of fever to their health care team. Cardiac ECGs with QTcF greater than 480msec ECGs with QTcF greater than 500msec 1. The dose should be interrupted. 2. If QTcF prolongation resolves to less than 481msec, resume treatment at the same dose level. 3. If QTcF greater than or equal to 481msec recurs, interrupt dose until QTcF resolves to less than 481msec and then resume ribociclib at the next lower dose level. If QTcF is greater than 500msec on at least 2 separate ECGs, interrupt ribociclib until QTcF is less than 481msec then resume ribociclib at next lower dose level. If QTcF interval prolongation to greater than 500msec or greater than 60msec change from baseline occurs in combination with torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia, permanently discontinue ribociclib Version 1 (Feb 2018) 4 Breast – Letrozole-Ribociclib Regimen 28 day cycle until disease progression or intolerance (twelve cycles will be set in ARIA) Ovarian ablation or suppression with a LHRH agonist is mandatory is patients who are pre or peri menopausal due to the pharmacology of ribociclib and aromatase inhibitors in combination. This is not included in the regimen on ARIA. Drug Letrozole Ribociclib Dose 2.5mg per day 600mg per day Days Days 1-28 inclusive Days 1-21 inclusive Route Oral Oral Dose Information • Letrozole is available as 2.5mg tablets • Ribociclib is available as 200mg tablets Administration Information • Ribociclib should be taken with or without food. If the patient vomits or misses a dose, an additional dose should not be taken that day. The next prescribed dose should be taken at the usual time. Additional Information • The National Patient Safety Alert on oral chemotherapy (NPSA/2008/RRR001) mustbe followed in relation to ribociclib • It must be made clear to all staff, including those in the community, that ribociclib should only be prescribed under the supervision of a consultant oncologist • Ribociclib interacts with many other agents. Always check for drug interactions. • Ovarian ablation or suppression with a LHRH agonist is mandatory is patients who are pre or peri menopausal due to the pharmacology of ribociclib and aromatase inhibitors in combination. Coding • Procurement - X70.8 • Delivery – X73.1 References 1. Hortobagyi GN, Stemmer SN, Burris HA et al. Ribociclib as first line therapy for HR positive advanced breast cancer. N Engl J Med (2016); 375 (18): 1738-1748. Version 1 (Feb 2018) 5 Breast – Letrozole-Ribociclib REGIMEN SUMMARY Letrozole-Ribociclib Day One 1. Letrozole 2.5mg once a day for 28 days oral 2. Ribociclib 600mg once a day for 21 days oral Administration Instructions Oral chemotherapy Ribociclib is taken from day one to day 21 of a 28 day cycle. Take with or without food Version 1 (Feb 2018) 6 Breast – Letrozole-Ribociclib DOCUMENT CONTROL Version Date Amendment Written By Approved By 1 Feb 2018 None Dr Deborah Wright Pharmacist Dr Jenny Bradbury 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 Hospital 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 (Feb 2018) 7 Breast – Letrozole-Ribociclib
Url
/Media/UHS-website-2019/Docs/Chemotherapy-SOPs1/Breastcancer/Letrozole-Ribociclib.pdf

Exemestane-Ribociclib

Description
Chemotherapy Protocol Breast Cancer Exemestane-Ribociclib Regimen • Breast Cancer – Exemestane-Ribociclib Indication • Ribociclib in combination with an aromatase inhibitor is indicated for the treatment previously untreated, hormone receptor-positive, HER2- negative, locally advanced or metastatic breast cancer that is not amenable to curative treatment and where; - the patient has had no prior treatment with a CDK 4/6 inhibitor unless either palbociclib has had to be stopped within 3 months of its start solely as a consequence of dose-limiting toxicity and in the clear absence of disease progression or ribociclib has been received as part of the compassionate use scheme and the patient meets all the other criteria - the patient is male or is female and either post-menopausal or if pre- or perimenopausal has undergone ovarian ablation or suppression with LHRH agonist treatment - the patient has had no previous hormone therapy for locally advanced or metastatic disease i.e. is hormone therapy naïve for locally advanced/metastatic breast cancer. Previous hormone therapy with anastrozole or letrozole whether as adjuvant therapy or as neoadjuvant treatment is allowed as long as the patient has had a disease-free interval of 12 months or more since completing treatment with anastrazole or letrozole. - WHO performance status of 0 – 2 Toxicity Treatment breaks of up to 6 weeks are allowed for ribociclib but solely to allow toxicities to settle. Drug Exemestane Ribociclib Adverse Effect Osteoporosis, headache, somnolence, hot flushes, alopecia, arthralgia, rash, vaginal dryness, asthenia, liver abnormalities, depression, insomnia Infection, myelosuppression, peripheral neuropathy, fatigue, mucositis, anorexia, eye disorders, venous thromboembolism, cadiac abnormalities The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Version 1 (Feb 2018) 1 Breast – Exemestane-Ribociclib Monitoring Drugs • FBC, LFTs and U&Es at baseline and then on day one of each cycle (every twenty-eight days). • For cycle one and two only the FBC and LFTs should be assessed on day one and fourteen of the cycle (the full cycle of ribociclib may be dispensed on day 1) • ECG should be assessed before initiating treatment with ribociclib. After initiating treatment, ECG should be repeated at approximately day 14 of the first cycle and at the beginning of the second cycle, then as clinically indicated. In case of QTcF prolongation during treatment, more frequent ECG monitoring is recommended. 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. The following is a general guide only. Haematological Dose modifications for haematological toxicity in the table below are for general guidance only. Always refer to the responsible consultant as any dose reductions or delays will be dependent on clinical circumstances and treatment intent. 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) Prior to prescribing cycle 1 the following criteria must be met. Criteria Neutrophils Platelets Eligible Level Equal to or more than 1.0x109/L Equal to or more than 100x109/L Thereafter dose adjustments for haematological toxicity are described in the table below; Version 1 (Feb 2018) 2 Breast – Exemestane-Ribociclib Toxicity Grade Ribociclib dose Haematological 1 or 2 No change Day 1: Delay one week. When recovered to NCI-CTC grade 2 or below restart at same dose Day 14 of first 2 cycles: continue current dose to complete 3 the cycle. Repeat the FBC on day 21. Consider dose reduction if the recovery to eligible levels takes 7 days or longer or there is recurrent NCI-CTC grade 3 neutropenia in subsequent cycles 3 with Delay until recovery to NCI-CTC grade 2 or below. Restart at fever next lower dose level 4 Delay until recovery to NCI-CTC grade 2 or below. Restart at next lower dose level Neutropenia was the most frequently reported adverse effect of ribociclib with a median onset of 15 days for any grade and 28 days for NCI-CTC grade 3 or 4. Median duration of severe neutropenia was seven days and most patients had their ribociclib dose reduced or held. No dose reductions are required for exemestane due to myelosuppression. Hepatic Impairment No dose change for exemestane is recommended in patients with mild hepatic disease. Caution is advised in patients with moderate to severe hepatic impairment Ribcoclib in Hepatic Impairment NCI-CTC Grade 1 No dose adjustment NCI-CTC Grade 2 No dose adjustment NCI-CTC Grade 3 Delay treatment until recovery to NCI-CTC grade 2 or below, then resume at the same dose level.If a NCI-CTC grade 2 toxicity recurs resume traement at the lower dose level NCI-CTC Grade 4 Interupt the dose until recovery to NCI-CTC grade 2 or below then resume at the next lowest dose level. Discontinue of NCI- CTC toxicity recurs. Combination If patients develop ALT and/or AST greater than 3xULN along with total bilirubin greater than 2xULN irrespective of baseline grade, discontinue ribociclib Renal Impairment No dose change is recommended for exemestane in patients with mild or moderate renal impairment. In patients with severe renal impairment, administration of exemestane should be performed with caution No dose adjustments of ribociclib are required for patients with mild to moderate renal impairment (creatinine clearance [CrCl] more than or equal to 30ml/min). Insufficient data are available in patients with severe renal impairment (CrCl less than 30ml/min) or requiring haemodialysis to provide any dose adjustment recommendation. Administer ribociclib to patients with severe renal impairment only after careful consideration of the potential benefits and risks and with close monitoring of signs of toxicity. Version 1 (Feb 2018) 3 Breast – Exemestane-Ribociclib Other Doses for other toxicities should be adjusted according to the table below; Dose Level 0 -1 -2 Ribociclib Dose (mg/day) 600 400 200 Letrozole dose (mg/day) 2.5 2.5 2.5 Ribociclib should be discontinued if the 200mg dose is not tolerated. Ribociclib Dose Adjustments Other non- NCI-CTC Grade 1 haematologic or 2 al or cardiac No dose toxicities adjustment is required. Initiate appropriate medical therapy and monitor as clinically indicated. NCI-CTC Grade 3 NCI-CTC Grade 4 Dose interruption until recovery to NCI-CTC grade 1 or below, then resume ribociclib at the same dose level. If NCI-CTC grade 3 recurs, resume ribociclib at the next lower dose level. Discontinue ribociclib Infections were reported more frequently in the ribociclib combination treatment arm versus the single agent aromatase inhibitor alone arm and may be severe. Patients should be warned of the increased risk of infection and promptly report any occurrences of fever to their health care team. Cardiac ECGs with QTcF greater than 480msec ECGs with QTcF greater than 500msec 1. The dose should be interrupted. 2. If QTcF prolongation resolves to less than 481msec, resume treatment at the same dose level. 3. If QTcF greater than or equal to 481msec recurs, interrupt dose until QTcF resolves to less than 481msec and then resume ribociclib at the next lower dose level. If QTcF is greater than 500msec on at least 2 separate ECGs, interrupt ribociclib until QTcF is less than 481msec then resume ribociclib at next lower dose level. If QTcF interval prolongation to greater than 500msec or greater than 60msec change from baseline occurs in combination with torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia, permanently discontinue ribociclib Version 1 (Feb 2018) 4 Breast – Exemestane-Ribociclib Regimen 28 day cycle until disease progression or intolerance (twelve cycles will be set in ARIA) Ovarian ablation or suppression with a LHRH agonist is mandatory is patients who are pre or peri menopausal due to the pharmacology of ribociclib and aromatase inhibitors in combination. This is not included in the regimen on ARIA. Drug Exemestane Ribociclib Dose 25mg per day 600mg per day Days Days 1-28 inclusive Days 1-21 inclusive Route Oral Oral Dose Information • Exemestane is available as 25mg tablets • Ribociclib is available as 200mg tablets Administration Information • Ribociclib should be taken with or without food. If the patient vomits or misses a dose, an additional dose should not be taken that day. The next prescribed dose should be taken at the usual time. Additional Information • The National Patient Safety Alert on oral chemotherapy (NPSA/2008/RRR001) mustbe followed in relation to ribociclib • It must be made clear to all staff, including those in the community, that ribociclib should only be prescribed under the supervision of a consultant oncologist • Ribociclib interacts with many other agents. Always check for drug interactions. • Ovarian ablation or suppression with a LHRH agonist is mandatory is patients who are pre or peri menopausal due to the pharmacology of ribociclib and aromatase inhibitors in combination. Coding • Procurement - X70.8 • Delivery – X73.1 References 1. Hortobagyi GN, Stemmer SN, Burris HA et al. Ribociclib as first line therapy for HR positive advanced breast cancer. N Engl J Med (2016); 375 (18): 1738-1748. Version 1 (Feb 2018) 5 Breast – Exemestane-Ribociclib REGIMEN SUMMARY Exemestane-Ribociclib Day One 1. Exemestane 25mg once a day for 28 days oral 2. Ribociclib 600mg once a day for 21 days oral Administration Instructions Oral chemotherapy Ribociclib is taken from day one to day 21 of a 28 day cycle. Take with or without food Version 1 (Feb 2018) 6 Breast – Exemestane-Ribociclib DOCUMENT CONTROL Version Date Amendment Written By Approved By 1 Feb 2018 None Dr Deborah Wright Pharmacist Dr Jenny Bradbury 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 Hospital 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 (Feb 2018) 7 Breast – Exemestane-Ribociclib
Url
/Media/UHS-website-2019/Docs/Chemotherapy-SOPs1/Breastcancer/Exemestane-Ribociclib.pdf

Anastrozole-Ribociclib

Description
Chemotherapy Protocol Breast Cancer Anastrozole-Ribociclib Regimen • Breast Cancer – Anastrozole-Ribociclib Indication • Ribociclib in combination with an aromatase inhibitor is indicated for the treatment previously untreated, hormone receptor-positive, HER2- negative, locally advanced or metastatic breast cancer that is not amenable to curative treatment and where; - the patient has had no prior treatment with a CDK 4/6 inhibitor unless either palbociclib has had to be stopped within 3 months of its start solely as a consequence of dose-limiting toxicity and in the clear absence of disease progression or ribociclib has been received as part of the compassionate use scheme and the patient meets all the other criteria - the patient is male or is female and either post-menopausal or if pre- or perimenopausal has undergone ovarian ablation or suppression with LHRH agonist treatment - the patient has had no previous hormone therapy for locally advanced or metastatic disease i.e. is hormone therapy naïve for locally advanced/metastatic breast cancer. Previous hormone therapy with anastrozole or letrozole whether as adjuvant therapy or as neoadjuvant treatment is allowed as long as the patient has had a disease-free interval of 12 months or more since completing treatment with anastrazole or letrozole. - WHO performance status of 0 – 2 Toxicity Treatment breaks of up to 6 weeks are allowed for ribociclib but solely to allow toxicities to settle. Drug Anastrozole Ribociclib Adverse Effect Osteoporosis, headache, somnolence, hot flushes, alopecia, arthralgia, rash, vaginal dryness, asthenia, liver abnormalities, depression, insomnia Infection, myelosuppression, peripheral neuropathy, fatigue, mucositis, anorexia, eye disorders, venous thromboembolism, cadiac abnormalities The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Version 1 (Feb 2018) 1 Breast – Anastrozole-Ribociclib Monitoring Drugs • FBC, LFTs and U&Es at baseline and then on day one of each cycle (every twenty-eight days). • For cycle one and two only the FBC and LFTs should be assessed on day one and fourteen of the cycle (the full cycle of ribociclib may be dispensed on day 1) • ECG should be assessed before initiating treatment with ribociclib. After initiating treatment, ECG should be repeated at approximately day 14 of the first cycle and at the beginning of the second cycle, then as clinically indicated. In case of QTcF prolongation during treatment, more frequent ECG monitoring is recommended. 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. The following is a general guide only. Haematological Dose modifications for haematological toxicity in the table below are for general guidance only. Always refer to the responsible consultant as any dose reductions or delays will be dependent on clinical circumstances and treatment intent. 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) Prior to prescribing cycle 1 the following criteria must be met. Criteria Neutrophils Platelets Eligible Level Equal to or more than 1.0x109/L Equal to or more than 100x109/L Thereafter dose adjustments for haematological toxicity are described in the table below; Version 1 (Feb 2018) 2 Breast – Anastrozole-Ribociclib Toxicity Grade Ribociclib dose Haematological 1 or 2 No change Day 1: Delay one week. When recovered to NCI-CTC grade 2 or below restart at same dose Day 14 of first 2 cycles: continue current dose to complete 3 the cycle. Repeat the FBC on day 21. Consider dose reduction if the recovery to eligible levels takes 7 days or longer or there is recurrent NCI-CTC grade 3 neutropenia in subsequent cycles 3 with Delay until recovery to NCI-CTC grade 2 or below. Restart at fever next lower dose level 4 Delay until recovery to NCI-CTC grade 2 or below. Restart at next lower dose level Neutropenia was the most frequently reported adverse effect of ribociclib with a median onset of 15 days for any grade and 28 days for NCI-CTC grade 3 or 4. Median duration of severe neutropenia was seven days and most patients had their ribociclib dose reduced or held. No dose reductions are required for anastrozole due to myelosuppression. Hepatic Impairment No dose change for anastrozole is recommended in patients with mild hepatic disease. Caution is advised in patients with moderate to severe hepatic impairment Ribcoclib in Hepatic Impairment NCI-CTC Grade 1 No dose adjustment NCI-CTC Grade 2 No dose adjustment NCI-CTC Grade 3 Delay treatment until recovery to NCI-CTC grade 2 or below, then resume at the same dose level.If a NCI-CTC grade 2 toxicity recurs resume traement at the lower dose level NCI-CTC Grade 4 Interupt the dose until recovery to NCI-CTC grade 2 or below then resume at the next lowest dose level. Discontinue of NCI- CTC toxicity recurs. Combination If patients develop ALT and/or AST greater than 3xULN along with total bilirubin greater than 2xULN irrespective of baseline grade, discontinue ribociclib Renal Impairment No dose change is recommended for anastrozole in patients with mild or moderate renal impairment. In patients with severe renal impairment, administration of anastrozole should be performed with caution No dose adjustments of ribociclib are required for patients with mild to moderate renal impairment (creatinine clearance [CrCl] more than or equal to 30ml/min). Insufficient data are available in patients with severe renal impairment (CrCl less than 30ml/min) or requiring haemodialysis to provide any dose adjustment recommendation. Administer ribociclib to patients with severe renal impairment only after careful consideration of the potential benefits and risks and with close monitoring of signs of toxicity. Version 1 (Feb 2018) 3 Breast – Anastrozole-Ribociclib Other Doses for other toxicities should be adjusted according to the table below; Dose Level 0 -1 -2 Ribociclib Dose (mg/day) 600 400 200 Anastrozole dose (mg/day) 1 1 1 Ribociclib should be discontinued if the 200mg dose is not tolerated. Ribociclib Dose Adjustments Other non- NCI-CTC Grade 1 haematologic or 2 al or cardiac No dose toxicities adjustment is required. Initiate appropriate medical therapy and monitor as clinically indicated. NCI-CTC Grade 3 NCI-CTC Grade 4 Dose interruption until recovery to NCI-CTC grade 1 or below, then resume ribociclib at the same dose level. If NCI-CTC grade 3 recurs, resume ribociclib at the next lower dose level. Discontinue ribociclib Infections were reported more frequently in the ribociclib combination treatment arm versus the single agent aromatase inhibitor alone arm and may be severe. Patients should be warned of the increased risk of infection and promptly report any occurrences of fever to their health care team. Cardiac ECGs with QTcF greater than 480msec ECGs with QTcF greater than 500msec 1. The dose should be interrupted. 2. If QTcF prolongation resolves to less than 481msec, resume treatment at the same dose level. 3. If QTcF greater than or equal to 481msec recurs, interrupt dose until QTcF resolves to less than 481msec and then resume ribociclib at the next lower dose level. If QTcF is greater than 500msec on at least 2 separate ECGs, interrupt ribociclib until QTcF is less than 481msec then resume ribociclib at next lower dose level. If QTcF interval prolongation to greater than 500msec or greater than 60msec change from baseline occurs in combination with torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia, permanently discontinue ribociclib Version 1 (Feb 2018) 4 Breast – Anastrozole-Ribociclib Regimen 28 day cycle until disease progression or intolerance (twelve cycles will be set in ARIA) Ovarian ablation or suppression with a LHRH agonist is mandatory is patients who are pre or peri menopausal due to the pharmacology of ribociclib and aromatase inhibitors in combination. This is not included in the regimen on ARIA. Drug Anastrozole Ribociclib Dose 1mg per day 600mg per day Days Days 1-28 inclusive Days 1-21 inclusive Route Oral Oral Dose Information • Anastrozole is available as 1mg tablets • Ribociclib is available as 200mg tablets Administration Information • Ribociclib should be taken with or without food. If the patient vomits or misses a dose, an additional dose should not be taken that day. The next prescribed dose should be taken at the usual time. Additional Information • The National Patient Safety Alert on oral chemotherapy (NPSA/2008/RRR001) mustbe followed in relation to ribociclib • It must be made clear to all staff, including those in the community, that ribociclib should only be prescribed under the supervision of a consultant oncologist • Ribociclib interacts with many other agents. Always check for drug interactions. • Ovarian ablation or suppression with a LHRH agonist is mandatory is patients who are pre or peri menopausal due to the pharmacology of ribociclib and aromatase inhibitors in combination. Coding • Procurement - X70.8 • Delivery – X73.1 References 1. Hortobagyi GN, Stemmer SN, Burris HA et al. Ribociclib as first line therapy for HR positive advanced breast cancer. N Engl J Med (2016); 375 (18): 1738-1748. Version 1 (Feb 2018) 5 Breast – Anastrozole-Ribociclib REGIMEN SUMMARY Anastrozole-Ribociclib Day One 1. Anastrozole 1mg once a day for 28 days oral 2. Ribociclib 600mg once a day for 21 days oral Administration Instructions Oral chemotherapy Ribociclib is taken from day one to day 21 of a 28 day cycle. Take with or without food Version 1 (Feb 2018) 6 Breast – Anastrozole-Ribociclib DOCUMENT CONTROL Version Date Amendment Written By Approved By 1 Feb 2018 None Dr Deborah Wright Pharmacist Dr Jenny Bradbury 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 Hospital 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 (Feb 2018) 7 Breast – Anastrozole-Ribociclib
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