Weekly Cisplatin + Radiotherapy - Interlace study -

Transcription

1 Weekly Cisplatin + Radiotherapy - Interlace study - A phase III multicentre trial of weekly induction chemotherapy followed by standard chemoradiation versus standard chemoradiation alone in patients with advanced cervical cancer **** See protocol for further details**** 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 Advanced cervical cancer Treatment Intent Radical Anti-Emetics Pre-chemotherapy 3 Post-chemotherapy C Day 1 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 (Maximum dose is 70mg) 40mg/m 2 AUTHORISED BY: Dr M Persic PAGE 1 of 6 Intravenous infusion in 500ml 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

2 Frequency & duration: weekly for 5 weeks maximum, commencing in the first week of radiotherapy or as soon as blood counts have recovered from induction chemotherapy. Refer to protocol as to when patients are treated depends whether randomisation was to the investigational arm or standard arm. Notes: 1. Prior to treatment, the following must apply: ANC > 1.5 x 10 9 /L (inclusion criteria) but > 1.0 x 10 9 /L prior to subsequent cycles Platelets > 100 x 10 9 /L (inclusion criteria) but > 75 x 10 9 /L prior to subsequent cycles Adequate renal function, defined as GFR > 60ml/min calculated using the wright equation (or > 50ml/min for radioisotope GFR assessment see appendix IV protocol and below) Total bilirubin < 1.25 ULN AST or ALT < 2.5 x ULN 2. FBC, U&E s (including magnesium & calcium) and LFT s must be performed prior to each cycle (ideally this is within 36 hours of treatment but biochemistry may be done up to 72 hours before treatment providing all indices are stable and not significantly different). Please refer to the Protocol. 3. Cisplatin is given concurrently with radiotherapy. See protocol for further details on the radiotherapy treatment. 4. Cisplatin infusion should ideally commence prior to daily radiotherapy fraction. 5. Accurate fluid balance sheet must be kept. 6. Urine output should be maintained at > 100ml/hour before (for at least 2 hours), during and after chemotherapy (8 hours). 7. 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 AUTHORISED BY: Dr M Persic PAGE 2 of 6

3 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. 8. Ensure Cisplatin is commenced by hours at the latest so an adequate renal output can be maintained. 9. Advise patients to drink at least 2 litres of fluid over next 24 hours. 10. For those patients unable to tolerate day case regime, due to rapid hydration give: Pre-hydration sodium chloride 0.9% 1000ml over 4 hours Post-hydration sodium chloride 0.9% 3000ml over 18 hours. 11. The interval from the last dose of induction chemotherapy to the start of cisplatin should be a minimum of 7 days to allow blood counts to recover. Where daily radiotherapy is being delivered (Monday Friday), it is suggested that cisplatin is given on a Monday, Tuesday or Wednesday of each week to maximise the potential radiosensitizing effect. Cisplatin must not be given on the same day as brachytherapy. 12. Dose banding for cisplatin is as per local policy, therefore National Dose Banding tables should be used. 13. For information on supportive & contraindicated medication in the study refer to section 8.2 & 8.3 of the Protocol, respectively. 14. Dose modifications for haematological toxicity Full dose of cisplatin will be given concomitantly with radiotherapy starting in week 7 for those patients on the investigational arm providing ANC count 1.0 x 10 9 /L and platelets 75 x 10 9 /L within 36 hours of treatment. If these levels are not reached the following dose modifications (based on the absolute drug dose) are recommended: AUTHORISED BY: Dr M Persic PAGE 3 of 6

4 Dose modifications for haematological toxicity during induction chemotherapy (Table 5 from Protocol) Haematological toxicity Cisplatin weekly No toxicity during cycle 100% dose (40mg/m 2 ) Day 1 ANC <1.0 or platelets <75 If cisplatin omitted on 2 occasions If further delays despite dose modification Febrile neutropenia ( grade 3 ) or ANC <0.5 lasting >7 days 2 nd occurrence of febrile neutropenia / ANC <0.5 lasting >7 days Delay for 24 hours. If still no recovery omit for 1 week. Continue at 80% of the absolute dose Discontinue cisplatin Hold for 1 week, if ANC resolves to grade 1 resume at 80% dose. If ANC does not resolve to grade 1 discontinue cisplatin Discontinue cisplatin All reasonable efforts must be made to ensure that the radiotherapy treatment continues without interruption. The use of GCSF is permitted at the investigator s discretion. GCSF should not be given within 24 hours pre or post chemotherapy treatment. 15. Dose modifications for non-haematologocal toxicity Hypersensitivity Patients who experience a Grade 3 or 4 allergic reaction to cisplatin should discontinue cisplatin and continue with radiation alone. AUTHORISED BY: Dr M Persic PAGE 4 of 6

5 Renal toxicity Dose modifications for renal toxicity during chemoradiation (Table 7 from Protocol) GFR (ml/min) Dose of cisplatin 50 ml/min if measured or 100% 60ml/min if calculated 50 ml/min if measured or 100% but consider slower infusion and 60 if calculated but < 75% of baseline extra hydration GFR <50 ml/min if measured or Omit <60ml/min if calculated If omitted on 1 occasion but recovers to 80% dose, consider slower infusion and > 50 ml/min if measured or >60ml/min if extra hydration calculated within 7 days If omitted on 1 occasion and no Discontinue permanently, recovery to > 50 ml/min if measured or continue radiation only >60ml/min if calculated within 7 days of initial fall During delays or breaks in cisplatin patients should continue with radical radiotherapy alone. Peripheral neuropathy Peripheral neuropathy > Grade 2 omit cisplatin for one week. If recovery occurs to Grade 1 continue with cisplatin at 80% of the dose. If further occurrence despite dose reduction, discontinue cisplatin and continue with radiation alone. Ototoxocity Tinnitus or impaired hearing Grade 2 hold until recovery to Grade 1. Then continue at 80% of the absolute dose. Where possible audiometry should be performed to document hearing loss. AUTHORISED BY: Dr M Persic PAGE 5 of 6

6 Gastrointestinal toxicity Patients with Grade 3 or 4 anorexia, nausea, vomiting, constipation, diarrhoea or other gastrointestinal events should be managed according to local guidelines. Hold cisplatin until toxicity resolves to Grade 1 and then either continue with full dose cisplatin with increased antiemetic cover or at 80% of the absolute dose (at investigator s discretion). If further occurrence despite dose reduction then discontinue cisplatin and continue radiation alone. Every effort must be made to continue the radiation therapy without interruption. 16. Additional medication for intercurrent illness or to manage the side effects of chemotherapy and /or radiotherapy may be prescribed at the investigator s discretion. References: 1. Interlace study Protocol EUDRAT no , version 5.0, 1 st September AUTHORISED BY: Dr M Persic PAGE 6 of 6