E 90 C followed by Weekly Paclitaxel Available for Routine Use in Burton in-patient Derby in-patient Burton day-case Derby day-case Burton community Derby community Burton out-patient Derby out-patient Indication Treatment Intent Breast Cancer Neoadjuvant, adjuvant E 90 C Anti-Emetics Pre-chemotherapy 3 Post-chemotherapy C Day 1 Epirubicin 90mg/m 2 Intravenous bolus Frequency & Duration Cyclophosphamide 600mg/m 2 Intravenous bolus Every 3 weeks for a maximum of 4 cycles FOLLOWED BY Weekly Paclitaxel Anti-Emetics Pre-chemotherapy 3 Post-chemotherapy Dexamethasone 2mg OD for 2 days + Metoclopramide 10mg QDS for 2 days then PRN Day 1 Dexamethasone 8mg Slow intravenous bolus (30 minutes prior to paclitaxel) Ranitidine 50mg Intravenous bolus (30 minutes prior to paclitaxel) Chlorphenamine 10mg Intravenous bolus (30 minutes prior to paclitaxel) Paclitaxel 80mg/m 2 Intravenous infusion in 250ml of Sodium Chloride 0.9% or Dextrose 5% Infusion in a PVC-Free infusion bag via a low-absorption set using a 0.2micron end-line filter over 60 minutes Frequency & Every 7 days for a maximum of 12 cycles Duration REVIEWED BY C Ward AUTHORISED BY: Dr R Vijayan, PAGE 1 of 5
Notes: E 90 C 1. FBC, U&Es and LFTs must be taken prior to Day 1 of each cycle. Following a toxicity assessment treatment may be given if: Neutrophils > 1.0 x 10 9 /L Platelets > 100 x 10 9 /L 2. Haematological Toxicity Neutrophils Platelets Dose 1.0 & 100 100% dose < 1.0 & / or < 100 Delay for 1 week. Repeat FBC - if recovered to above these levels, resume treatment with 100% dose In neoadjuvant/adjuvant treatment, dose reduction and delays can compromise outcome. GCSF should be considered if more than one delay and/or before dose reduction. If in doubt, seek Consultant advice. If during the preceding cycle, the patient has experienced neutrophils < 0.5 x 109 /L or has febrile neutropenia diagnosed, GCSF should be considered. If despite GCSF treatment, febrile neutropenia occurs or a dose delay is required - seek Consultant advice and consider dose reduction by 25% If platelets persistently < 100 x 109 /L on Day 1 despite dose delay - seek Consultant advice and consider dose reduction by 25% 3. Non-haematological Toxicities Renal Impairment - Cyclophosphamide Creatinine Clearance (ml/min) Cyclophosphamide Dose > 20 100% dose 10-20 75% dose < 10 Discuss with consultant and consider 50% dose Hepatic Impairment Epirubicin Bilirubin (micromol/l) Epirubicin Dose 24-51 Give 50% 51 85 Give 25% > 85 Omit REVIEWED BY C Ward AUTHORISED BY: Dr R Vijayan, PAGE 2 of 5
Weekly Paclitaxel 1. At each attendance the following investigations are required:- FBC U&Es LFTs 2. Following a toxicity assessment treatment may be given if: Neutrophils > 1 x10 9 /L Platelets > 75 x 10 9 /L 3. Haematological Toxicity Neutrophils Platelets Dose 1.0 & 100 100% dose 1.0 & 75-99 Discuss with Consultant treatment can be considered on medical advice. Or consider treatment delay for 1 week. Repeat FBC, if platelets recover to 100 x 10 9 /L, resume treatment at 100% dose < 1.0 & / or < 75 Delay for 1 week. Repeat FBC, if recovered to above these levels, resume treatment with 75% dose for all subsequent cycles. In neoadjuvant/adjuvant treatment, dose reduction and delays can compromise outcome. GCSF should be considered if more than one delay and/or before dose reduction. If in doubt, seek Consultant advice. If during the preceding cycle, the patient has experienced neutrophils <0.5 x 10 9 /L or has febrile neutropenia diagnosed, GCSF should be considered. If despite GCSF treatment, febrile neutropenia occurs or a dose delay is required seek Consultant advice and consider dose reduction by 25% If platelets persistently < 100 x 10 9 /L on Day 1 despite dose delay - seek Consultant advice and consider dose reduction by 25% 4. Non-haematological Toxicities Hepatic Impairment Paclitaxel Bilirubin (micromol/l) Dose 22-26 Give 75 80% dose 27 51 Give 40 45% dose > 51 Give 30% dose REVIEWED BY C Ward AUTHORISED BY: Dr R Vijayan, PAGE 3 of 5
Peripheral Neuropathy Whilst neurotoxicity is rare occasionally problems have been experienced in patients with diabetes or pre-existing occult neuropathic deficits. The following dose reductions are advised: Degree of neuropathy Paclitaxel Dose Neuropathy interfering with function 65mg/m 2 (CTC grade 2) Impairment of daily activities of daily living (CTC grade 3) (Approx. 80% of full dose) Omit 5. Frequent vital sign monitoring during the Paclitaxel administration is recommended. Paclitaxel-related acute hypersensitivity reactions Despite routine prophylaxis with antihistamines and steroids etc., 2-4% of patients will suffer hypersensitivity reactions to paclitaxel. These usually occur in the first 5-10 minutes of the first or second infusion. Adrenaline (1ml/1:1000 IM) should be available, as should antihistamines, dexamethasone and oxygen. Whilst mild/moderate reaction may subside with further steroids and antihistamines, allowing successful re-challenge, this practice should be avoided if the severity of the initial reaction was such that adrenaline was required. Degree of reaction Mild symptoms Skin rash, flushing, localised pruritus Moderate symptoms Generalised pruritus or rash, mild dyspnoea, mild hypotension Severe symptoms Bronchospasm, generalised urticaria, angio-oedema, hypotension (systolic <80mmHg) Recommended Action Reduce infusion rate Treat with further IV chlorphenamine 10mg Monitor until recovery Then re-challenge Stop paclitaxel infusion Treat with IV hydrocortisone 100mg and IV chlorphenamine 10mg Re-challenge after recovery Stop paclitaxel infusion Treat with IM adrenaline (1ml 1:1000), IV hydrocortisone 100mg and IV chlorphenamine 10mg REVIEWED BY C Ward AUTHORISED BY: Dr R Vijayan, PAGE 4 of 5
References 1. 6. Alcohol content Paclitaxel contains up to 21g (approx. 2.5 units) of ethanol per maximum dose. Patients should be advised not to drive on the day of treatment. Consider alternative chemotherapy agents for patients where alcohol content is a concern. 7. If HER-2 +ve disease, subcutaneous trastuzumab (3-weekly for 1 year) may be commenced at the same time as paclitaxel. REVIEWED BY C Ward AUTHORISED BY: Dr R Vijayan, PAGE 5 of 5