ABVD for Hodgkin s Lymphoma (LYMWOS008/1)

Transcription

1 West of Scotland Cancer Network Chemotherapy Protocol Indication 1 st line treatment of Hodgkin s Lymphoma Eligibility Criteria ABVD for Hodgkin s Lymphoma (LYMWOS008/1) Confirmed diagnosis of Hodgkin s Lymphoma Treatment intent Curative Pre-treatment evaluation 1. Full staging tests. 2. Assessment of patient s Performance status. 3. Baseline pulmonary function tests are recommended 4. Cardiac ECHO for all patients > 60 years or with a history of heart disease or hypertension. 5. Provision of verbal and written information. 6. Informed consent. 7. HepB, C and HIV status. 8. Height, weight and BSA. 9. Baseline investigations FBC, U&E s, LFT s Creatinine clearance Page 1 of 6

2 Regimen Drug Dose Route Administration Frequency Treatment Days Doxorubicin 25mg/m 2 IV Injection into the side arm of a fast flowing infusion of Bleomycin 10,000 IV * Infusion over one units/m 2 hour in 100ml Vinblastine 6mg/m 2 IV Injection into the side arm of a fast flowing infusion of Dacarbazine 375mg/m 2 IV Infusion over one hour in 500ml Repeat every 28 days for 2-8 cycles, depending on stage. Maximum Cumulative dose Once daily Days 1 & mg/m 2 Once daily Days 1 & 15 ^ Once daily Days 1 & 15 N/A Once daily Days 1 & 15 N/A * The IM route of administration has been reported to be associated with reduced pulmonary toxicity. It is a valid alternative to slow intravenous administration and is favoured by some clinicians. No comment on efficacy of IM bleomycin is made as most large published trials have used IV bleomycin. ^ The risk of bleomycin induced pulmonary fibrosis is dose related and more commonly occurs in the elderly and at cumulative doses greater than 300,000 units. Premedication 100mg IV Hydrocortisone (15 min pre-bleomycin) and 1g paracetamol (1 hour prebleomycin), where the patient has had a previous reaction. Supportive therapy Emetogenic risk: High (>90%) Refer to local guideline for management. Allopurinol 300mg daily for 7 days (100mg if Cr Cl < 20ml/min) for cycles 1 and 2 unless contraindicated. Mouthcare as per local policy GCSF primary prophylaxis is not recommended. Given only if patient has additional risk factors (see GCSF guideline) GCSF secondary prophylaxis may be considered but may increase risk of pulmonary toxicity with bleomycin, see haematological toxicities. Adverse effects Very Common Incidence > 10% Common Incidence 1-10% Haematological: myelosuppression (anaemia, thrombocytopenia, neutropenia) Gastrointestinal: nausea/vomiting, mucositis, stomatitis. Skin: alopecia, hyperpigmentation. Local: thrombophlebitis. Other: discolouration of urine, acute febrile reactions. Cardiovascular: congestive heart failure, ECG abnormalities. Respiratory: interstitial pneumonitis, pulmonary fibrosis. Gastrointestinal: constipation, paralytic ileus. Skin: rash, photosensitivity. Page 2 of 6

3 This is not an exhaustive list. Please refer to SPC, at for more detailed information. Extravasation risk category: Drug Doxorubicin Bleomycin Vinblastine Dacarbazine Category Vesicant Neutral Vesicant Vesicant In the event of an extravasation, refer to local policy. Precautions & contraindications Drug interactions Known allergy to any of the drug regimen. Baseline ejection fraction < 45% or >20% reduction on repeat ECHO. be susceptible to more frequent or severe bleomycin induced toxicity. Contraceptive measures in both sexes is advised. Contraindicated in pregnancy and breastfeeding. Caution in renal impairment for bleomycin, dacarbazine and doxorubicin. Caution in hepatic impairment for bleomycin, dacarbazine, doxorubicin and vinblastine. Drug Increased Effect / Toxicity Decreased Effect Doxorubicin Azole antifungals, chlorpromazine, ciclosporin, ciprofloxacin, clarithromycin, delaviridine, diclofenac, doxycycline, erythromycin, fluoxetine, imatinib, isoniazid, miconazole, nefazodone, nicardipine, paroxetine, pergolide, propofol, protease inhibitors, quinine, quinidine, ritonavir, ropinirole, telithromycin, verapamil and other inhibitors of CYP2D6 or 3A4. Doxorubicin may increase the levels/effects of bupropion, promethazine, propofol, selegiline, sertraline and other CYP2B6 substrates. Aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, rifamycins, St. John s wort and other CYP3A4 inducers. Doxorubicin may decrease the levels/effects of digoxin and zidovudine. Bleomycin None documented Bleomycin may decrease the effects of digoxin and phenytoin. Vinblastine Azole antifungals, ciprofloxacin, clarithromycin, diclofenac, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, verapamil and other inhibitors of CYP3A4. Dacarbazine Amiodarone, ciprofloxacin, disulfiram, fluvoxamine, isoniazid, ketoconazole, lomefloxacin, miconazole, ofloxacin, rofecoxib and other inhibitors of CYP1A2 or 2E1. Investigations prior to subsequent cycles 1. FBC, U&E s, LFT s. Aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, rifamycins, St John s wort and other CYP 3A4 inducers. Aminoglutethimide, carbamazepine, phenobarbital, phenytoin, rifamycins and other CYP1A2 inducers. Page 3 of 6

4 2. Creatinine clearance. 3. Performance status. 4. Assessment of toxicity, documented by CTCAE version Weight (Re-calculate surface area if > 10% change from baseline). 6. Full physical examination, including clinical assessment of disease response. 7. All patients complaining of shortness of breath should have a CXR and PFT's prior to further administration of bleomycin. If any clinical signs or CXR evidence of pulmonary infiltration/fibrosis develop or if transfer factor < 50% of predicted value, bleomycin should be discontinued. Dose modifications Haematological * Result Value Action Platelets x 10 9 /L < 100 Delay Neutrophils <1.0 Delay. Consider GCSF. Grade 4 neutropenia with sepsis Consider GCSF * It is appreciated that there is published evidence supporting continuous administration of ABVD without the need for dose adjustments or GCSF. British Journal of Haematology, 137, This is an acceptable alternative approach. Renal Drug GFR (ml/min) % of full dose Comments Bleomycin >50 100% % <10 50% Dacarbazine >60 100% % % 30 70% Doxorubicin < 10 Clinical decision Page 4 of 6

5 Hepatic Drug Bilirubin AST/ALT % of full dose Comments Bleomycin Clinical decision Dacarbazine Contraindicated in severe hepatic impairment. Doxorubicin ULN-51 50% % >85 Omit dose 2-3xULN 75% Vinblastine ULN-51 or % >51 and normal 50% >51 and >180 Omit dose Others Toxicity Grade Action Neuropathies III or IV Consider dose reducing vinblastine Pulmonary toxicity Consider omitting bleomycin Evaluation of response to treatment Repeat CT scan after 2-3 cycles. PET scan after 2 cycles in advanced disease, according to CMG. PET scan at end of treatment, if residual mass and no interim PET. References 1. Johnson PWM, Radford JA, Cullen MH et al. Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin s lymphoma: results of the United Kingdom Lymphoma Group LY09 Trial. Journal of Clinical Oncology 2005; 23(36): The North London cancer Network. Dosage Adjustments for Cytotoxics in Hepatic Impairment. Nov The North London cancer Network. Dosage Adjustments for Cytotoxics in Renal Impairment. Nov Salimando DA. Drug Information Handbook for Oncology. 4 th ed. Ohio: Lexi- Comp; Allwood M, Stanley A, Wright P. The Cytotoxic Handook. 4 th ed. Oxon: Radcliffe Medical Press ; Kris MG, Hesketh PJ, Somerfield MR et al. American Society of Clinical Oncology Guidelines for Antiemetics in Oncology: Update JCO 2006; 24(18): Summary of Product Characteristics for Bleomycin, dacarbazine, doxorubicin and vinblastine. November BNF 52. Page 5 of 6

6 Document control Prepared by Craig Richardson and Kelly Baillie Checked by Dr L Mitchell and Dr P Tansey Approved by Dr Pam McKay, Lead Clinician Haeamto-oncology MCN Issue date October 2008 Review date October 2010 Reference/version no. LYMWOS008/1 Replaces Not applicable Page 6 of 6