Gemcitabine + Cisplatin Regimen

Transcription

1 Gemcitabine + Cisplatin Regimen 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 Urothelial Treatment Intent Neo-adjuvant or Palliative Anti-Emetics Pre-chemotherapy Day 1 2 Day 2 3 Day 8 & 15 2 Post-chemotherapy Day 1 C Day 8 & 15 B Day 1 Gemcitabine 1000mg/m 2 Intravenous infusion in 250ml Day 2 Sodium chloride 0.9% 1000ml Intravenous infusion over 1 hour Sodium chloride 0.9% 500ml Intravenous infusion over 30 (if urine output remains low) Mannitol 10% 100ml Intravenous infusion over 10 Provided urine output is satisfactory (see notes) Cisplatin 70mg/m 2 Intravenous infusion in 1000ml sodium chloride 0.9% over 60 (protect infusion from light) Mannitol 10% 100ml Intravenous infusion over 10 Sodium chloride 0.9% + 20mmol magnesium sulphate + 20 mmol potassium chloride 1000ml Intravenous infusion over 2 hours PAGE 1 of 5

2 Day 8 Gemcitabine 1000mg/m 2 Intravenous infusion in 250ml Day 15 Gemcitabine 1000mg/m 2 Intravenous infusion in 250ml Frequency & duration: every 28 days for a maximum of 3 cycles (Neo-adjuvant) every 28 days for a maximum of 6 cycles (Palliative) Notes: 1. U&Es, & LFTs must be taken prior to Day 1 of each cycle 2. FBC must be taken prior to each dose 3. Following a toxicity assessment each cycle may be given if: Neutrophils > 1.0x10 9 /L Platelets >100x 10 9 /L If the above parameters are not met see overleaf for details of dose modifications (incl. days 8 & 15) 4. The GFR prior to the first treatment should routinely be > 60 ml/minute. Then prior to each cycle, GFR should be estimated or measured as deemed clinically appropriate e.g. Cockcroft Gault Formula Females: Males: 1.04 x (140 age) x weight (kg) serum creatinine (micromol/l) 1.23 x (140 age) x weight (kg) serum creatinine (micromol/l) For patients with body mass index (BMI) of 30 kg/m2 with stable serum creatinine values, the adjusted body weight (ABW) should be used to estimate the GFR i.e. PAGE 2 of 5

3 Ideal Body Weight Female IBW (kg) = Height in cm Male IBW (kg) = Height in cm 100 ABW = IBW + 0.4(actual weight IBW If the estimated serum creatinine clearance is <60 ml/minute, then a formal measurement of the GFR is required, using either a 24 hour urine collection or an isotopic clearance. If the isotopic clearance is measured then the value uncorrected for body surface area (BSA) should be used in dose calculations. 5. The GFR should be recalculated, or re-measured, for a. Renal toxicity (CTC Grade 2, serum creatinine >1.5 x ULN), b. Serum creatinine changes of 10% compared to baseline, or last creatinine value (whichever is most recent), c. Cycle 2, if there has been significant doubt about the true GFR at cycle 1 (according to clinical judgement). Cisplatin Dose Modifications for Impaired Renal Function Creatinine Clearance (ml/min) Cisplatin Dose (mg/m 2 ) % % <45 Omit 6. Accurate fluid balance sheet must be kept. 7. Urine output should be maintained at > 100ml/hour before, during & after chemotherapy. 8. Mannitol 10% infusion is the preferred diuretic. If urine output remains <100ml/hr, a further dose of 100ml may be given by intravenous infusion over 10. Urine output should increase within 30 of commencing the infusion. If urine output remains <100ml/hr after 30, a 10 mg stat IV bolus of Furosemide may be given to increase urine output. If 30 after the furosemide dose urine output has still not improved, the Consultant should be contacted for advice. PAGE 3 of 5

4 9. Ensure Cisplatin is commenced by 14.00hrs at the latest so an adequate renal output can be maintained. 10. Dose modifications Complete ANC and platelet count weekly in every cycle (on day 21 at least during the first 2 cycles). Day 1 ANC Platelets Gemcitabine/Cisplati n 1.5 And 100 Full doses If a patient needs 2 weeks for haematologic recovery, treatment should be continued with 75% of all three drugs if WBC 2.0 x 10 9 /L, ANC 1.0 x 10 9 /L and platelets are 75 x 10 9 /L. Days 8 & 15 ANC (x 10 9 /L) Platelet s Percentage dose of Gemcitabine 1.5 And % Dose 1.0 and % Dose 1.0 or 50 Withhold 25% dose reduction in both drugs if during the nadir one or more of the following occurs: Grade IV neutropenia (ANC 0.5 x 10 9 /L) with fever 38.5 C or Grade IV thrombocytopenia ( 10.0 x 10 9 /L) for more than 3 days or Thrombocytopenia with active bleeding during the nadir. If afebrile grade IV neutropenia is present on day 15 give prophylactic ciprofloxacin 500mg twice daily for 7 days. 11. Mucosal Toxicity Patients with grade 3 4 mucositis will have a 25% dose decrease of on days 1, 8 & Neurotoxicity Grade 3-4 neurotoxicity cisplatin should be discontinued and patients remain in the protocol as long as they continue to receive gemcitabine and no additional anti-cancer treatment is given. PAGE 4 of 5

5 13. Renal Toxicity GFR (ml/min) % dose of Gemcitabine % dose of Cisplatin 60ml/min ml/min to be given over 2 days 50ml/min Full dose gemcitabine unless the CTC grade for Creatinine is 3 ( 6 x ULN) in which case omit dose If GFR 50ml/min repeat after IV hydration (max 2 days), if still 50ml/min withhold during current cycle. 14. Other Toxicities Grade 1 2 Grade 3 Grade 4 no dose reductions 50% dose reductions in both drugs Patient may be withdrawn from the study at the investigators discretion. If patient continues under treatment, 50% dose reduction of both drugs should be considered. 15. Dosage adjustments in a cycle If day 1 of the cycle is delayed the cycle will not consider starting until the day the first dose is actually administered to the patient. If the day 8 dose is withheld or missed the cycle would continue per protocol with one dose not given. If day 15 is withheld or missed this would be considered to be the week of rest. The following week a dose would be administered if toxicity permits and considered day 1 of the new cycle. A patient who cannot be administered treatment after a delay of more than 2 weeks from the planned beginning of a new cycle must be discontinued from protocol treatment. 16. Alcohol content of gemcitabine Doses of gemcitabine not available as ready- made infusions contain up to approximately 11g of ethanol (1.5units). Patients should be advised not to drive on the day of treatment. Where alcohol content is a concern please contact pharmacy for advice about alternative formulations. References: 1. BA11 Trial Protocol (5 th Sept 2002) Version 6.2 PAGE 5 of 5