5-FU & Cisplatin + Cetuximab

Transcription

1 5-FU & Cisplatin + Cetuximab Available for Routine Use in Not routinely commissioned, each case requires prior documented approval before offering & commencing therapy from either: a) the relevant PCT or b) the relevant SHA Interim Cancer Drugs Fund panel Indication Primary metastatic/recurrent/relapsed head and neck cancers Treatment Intent Palliative Anti-Emetics Pre-chemotherapy 3+Akynzeo Post-chemotherapy C Day 1 Sodium chloride 0.9% 1000ml Intravenous infusion over 1 hour Sodium chloride 0.9% 500ml Intravenous infusion over 30 minutes (if urine output remains low) Mannitol 10% 100ml Intravenous infusion over 10 minutes Provided urine output is satisfactory (see notes) Cetuximab 400mg/m 2 (Cycle 1) 250mg/m 2 (Subesquent cycles) AUTHORISED BY: Dr R Vijayan & PAGE 1 of 7 Intravenous infusion over 2 hours (Cycle 1), subsequent cycles over 1 hour Cisplatin 80mg/m 2 Intravenous infusion in 1000ml sodium chloride 0.9% over 1 hour (protect infusion from light) Mannitol 10% 100ml Intravenous infusion over 10 minutes Sodium chloride 0.9% + 20mmol magnesium sulphate + 20 mmol potassium chloride 1000ml Intravenous infusion over 2 hours Followed By Day 1 5-Fluorouracil 2000mg/m 2 Intravenous infusion in 120ml sodium chloride 0.9% in 2.5ml/hr infusor device over 48 hours via PICC or Hickman line

2 Day 3 5-Fluorouracil 2000mg/m 2 Intravenous infusion in 120ml sodium chloride 0.9% in 2.5ml/hr infusor device over 48 hours via PICC or Hickman line Day 8 Cetuximab 250mg/m 2 Intravenous infusion over 1 hour Day 15 Cetuximab 250mg/m 2 Intravenous infusion over 1 hour Frequency & duration: every 21 days for a maximum of 6 cycles FOLLOWED BY Cetuximab monotherapy every 7 days until disease progression Notes: 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 > 1.0x10 9 /L Platelets > 100x10 9 /L 2. 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 AUTHORISED BY: Dr R Vijayan & PAGE 2 of 7

3 i.e. 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. 3. The GFR should be recalculated, or re-measured, for Renal toxicity (CTC Grade 2, serum creatinine >1.5 x ULN), Serum creatinine changes of 10% compared to baseline, or last creatinine value (whichever is most recent), Cycle 2, if there has been significant doubt about the true GFR at cycle 1 (according to clinical judgement). 4. If creatinine clearance is < 60mls/min the Cisplatin dose is adjusted as follows: 60 ml/min FULL dose Cisplatin ml/min 50% dose Cisplatin < 40 ml/min OMIT Cisplatin 5. 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 minutes. Urine output should increase within 30 minutes of commencing the infusion. If urine output remains <100ml/hr after 30 minutes, a 10 mg stat IV bolus of Furosemide may be given to increase urine output. If 30 minutes after the furosemide dose urine output has still not improved, the Consultant should be contacted for advice. 6. Ensure Cisplatin is commenced by hours at the latest so an adequate renal output can be maintained. 7. Patients must be advised to drink 2 litres of fluid over next 24 hours. 8. Urine output should be maintained at > 100 ml/hour before (for at least 2 hours from commencing hydration), during and after chemotherapy (8 hours). AUTHORISED BY: Dr R Vijayan & PAGE 3 of 7

4 9. Accurate fluid balance sheet must be kept. 10. If cisplatin is contra-indicated, substitute Carboplatin, see separate QACS protocol 11. Prior to each cetuximab infusion, patients must receive premedication with an antihistamine (e.g. Chlorphenamine 10mg intravenous bolus). 12. The line should be flushed with sodium chloride 0.9% NOT dextrose 5% prior to and following the cetuximab administration. 13. A nurse must be present in the immediate area during the first infusion of cetuximab and for one hour thereafter, and a physician within close proximity or immediately available by emergency bleep. 14. Close monitoring is required during the infusion and for at least 1 hour after the end of the infusion. Availability of resuscitation equipment must be ensured. 15. Cetuximab Infusion-related reactions Severe infusion-related reactions have been reported in patients treated with cetuximab. Symptoms usually occurred during the first infusion and up to 1 hour after the end of infusion, but may occur after several hours or with subsequent infusions. Treatment depends on the grade or severity of the reaction, as follows: CTC Grade Treatment Allergic/hypersensitivity reaction Grade 1 Decrease the cetuximab infusion rate by Transient flushing or rash, drug fever <38ºC 50% and monitor closely for any worsening The total infusion time for Cetuximab should Grade 2 Rash; flushing; urticaria; dyspnea; drug fever 38 C Grade 3 or Grade 4 Grade 3: Symptomatic bronchospasm, with not exceed 240 minutes Stop cetuximab infusion Administer bronchodilators, oxygen etc. as medically indicated Resume infusion at 50% of previous rate once allergic/hypersensitivity reaction has resolved or decreased to grade 1 in severity, and monitor closely for any worsening Stop cetuximab infusion immediately and disconnect infusion tubing from the patient AUTHORISED BY: Dr R Vijayan & PAGE 4 of 7

5 or without urticaria; parenteral medication(s) indicated; allergy related edema/angioedema; hypotension Grade 4: Anaphylaxis Administer epinephrine, bronchodilators, antihistamines, glucocorticoids, intravenous fluids, vasopressor agents, oxygen etc., as medically indicated Patients have to be withdrawn immediately from treatment and must not receive any further cetuximab treatment Once the infusion rate has been slowed for an allergic reaction, it should remain at the slower rate for all subsequent infusions. If the patient has a second allergic/hypersensitivity reaction on the slower infusion rate, the infusion should be stopped and no further cetuximab administered. If a patient receives a grade 3 or 4 allergic/hypersensitivity reaction at any time, cetuximab must be discontinued. It is recommended to warn patients of the possibility of such a late onset and instruct them to contact their physician if symptoms of an infusion-related reaction occur. Occurrence of a severe infusion-related reaction requires immediate and permanent discontinuation of cetuximab therapy and may necessitate emergency treatment 16. Skin reactions If a patient experiences a severe skin reaction ( grade 3; US National Cancer Institute - Common Toxicity Criteria, NCICTC), cetuximab therapy must be interrupted. Treatment may only be resumed, if the reaction has resolved to grade 2 If the severe skin reaction occurred for the first time, treatment may be resumed without any change in dose level. With the second and third occurrences of severe skin reactions, cetuximab therapy must again be interrupted. Treatment may only be resumed at a lower dose level (200 mg/m² after the second occurrence and 150 mg/m² after the third occurrence), if the reaction has resolved to grade 2. If severe skin reactions occur a fourth time or do not resolve to grade 2 during interruption of treatment, permanent discontinuation of cetuximab treatment is required AUTHORISED BY: Dr R Vijayan & PAGE 5 of 7

6 Grade 3 skin reactions Schematic of management of grade 3 skin reactions Delay infusion for 1 week Resolved to grade 2? YES Which grade 3? 1st 2nd 3rd 4th NO 2nd consecutive week Delay infusion for 1 week Dose at 250mg/m 2 Reduce dose to 200mg/m 2 Reduce dose to 150mg/m 2 Discontinue treatment 3rd consecutive week Discontinue treatment Suggested management of skin reactions: Grade 1 (Mild) 2 (Moderate) 3 (Severe) Comments Definition (NCI-CTC v2 skin reactions) Macular or papular eruption or erythema without associated symptoms Macular or papular eruption or erythema with pruritus or other associated symptoms; localised desquamation or other lesions covering < 50% of body surface area Symptomatic generalised erythroderma or macular, papular or vesiculareruption or desquamation covering 50% of body surface area Delay Cetuximab? No No Yes (until resolved to grade 2 or less, see flow chart above) Topical treatment Consider Yes Yes Systemic treatment Discuss with patient Yes Yes Treatment suggestions (if in doubt discuss with consultant and/or dermatologist) Topical Topical anti-acne or anti-rosacea products As for grade 1 plus: menthol in aqueous cream As for grade 2 and seek dermatology advise for severe Systemic Not usually indicated Oral antihistamines and oral tetracyclines cases Oral antihistamines and oral tetracyclines Oral corticosteroids themselves may induce acne-like rash or rosacea Topical corticosteroids applied to an acnelike rash may exacerbate local symptoms AUTHORISED BY: Dr R Vijayan & PAGE 6 of 7

7 17. Electrolyte disturbances Progressively decreasing serum magnesium levels have been observed leading to severe hypomagnesaemia in some patients. Hypomagnesaemia is reversible following discontinuation of cetuximab. Depending on severity, other electrolyte disturbances, mainly hypocalcaemia or hypokalaemia, have also been observed. Determination of serum electrolyte levels is recommended prior to and periodically during cetuximab treatment. Electrolyte repletion is recommended, as appropriate 18. Respiratory disorders Dyspnoea may occur in close temporal relationship to the cetuximab infusion as part of an infusion-related reaction, but has also been reported after several weeks of therapy, possibly related to the underlying disorder. Patients with advanced age, impaired performance status and underlying cardiac or pulmonary disorders may be at increased risk for dyspnoea, which may be severe and/or long-standing. If patients develop dyspnoea during the course of cetuximab treatment, it is recommended to investigate them for signs of progressive pulmonary disorders as appropriate. Individual cases of interstitial lung disorders of unknown causal relationship to cetuximab have been reported. If interstitial lung disease is diagnosed, cetuximab must be discontinued and the patient be treated appropriately References: 1. Clark P, on behalf of the MRC Upper GI Tract Cancer Group. Medical Research Council (MRC) randomised phase III trial of surgery with or without pre-operative chemotherapy in resectable cancer of the oesophagus. Br J Cancer, 2000; 83 (supplement 1):1, abstract CT2. 2. Merck Serono; Summary of Product Characteristics AUTHORISED BY: Dr R Vijayan & PAGE 7 of 7