Lymphoma group

ABVD
INDICATION Hodgkin lymphoma. Please refer to the bleomycin supportive care document.

TREATMENT INTENT Curative.

PRE-ASSESSMENT 1. 2. 3. 4. 5. 6. Ensure histology is confirmed prior to administration of chemotherapy and document in notes. Record stage of disease - CT scan (neck, chest, abdomen and pelvis) and/or PET-CT scan, presence or absence of B symptoms, clinical extent of disease. Bone marrow aspirate and trephine if Stage IIB – IV radiologically. Pulmonary function tests before course one and as clinically indicated (see bleomycin supportive care document). Blood tests - FBC, ESR, DAT, U&Es, LDH, urate, calcium, magnesium, creatinine, LFTs, glucose, Igs, β2 microglobulin, Hep B&C, EBV, CMV, VZV, HIV 1+2 after consent. Send a "group and save" sample to transfusion and inform patient and transfusion laboratory that they will require irradiated blood products for all future transfusions. Ensure card is attached to the patient's notes and copy given to the patient. Urine pregnancy test - before cycle 1 of each new chemotherapy course in women aged 12 – 55 years of age unless they have been sterilised or undergone a hysterectomy. ECG +/- Echo - if clinically indicated. Record performance status (WHO/ECOG). Record height and weight. Consent - ensure patient has received adequate verbal and written information regarding their disease, treatment and potential side effects. Document in medical notes all information that has been given. Obtain written consent prior to treatment. Fertility - it is very important the patient understands the potential risk of reduced fertility. All patients should be offered fertility advice (see fertility guidelines). Hydration - in patients with bulky disease pre-hydrate with sodium chloride 0.9% 1 litre over 4-6 hours. For patients at high risk of tumour lysis, refer to the tumour lysis protocol. Consider dental assessment / Advise dental check is carried out by patient's own dental practitioner before treatment starts. Treatment should be agreed in the relevant MDT.

7. 8. 9. 10. 11.

12. 13. 14. 15.

For early stage disease, classify into favourable or unfavourable – see treatment pathway.

1 of 4 This is a controlled document and therefore must not be changed or photocopied ABVD Authorised by Lymphoma lead Published: September 2008 Version Dr. Chris Hatton Reviewed: May 2010 3.4 Date: August 2012 Amended: June 2011 May & Aug 2012 Review: June 2013

Formal restaging including CT scan after 4. Day 15 DOXORUBICIN 25 mg/m2 iv bolus. Bleomycin should be omitted from courses 7 and 8. Day 15 DACARBAZINE 375 mg/m2 iv infusion in 250-500 ml sodium chloride 0. All drugs will be given at full dose and on schedule with no dose delays or reduction for haematological toxicity. Aim to treat to complete response + 2 courses. give 25% dose reduction If AST >3 x ULN. Day 1 BLEOMYCIN* 10. Patients who are unwell should be deferred by one week. If performing PET-CT scan at end of treatment.000 units/m2 in 100 ml sodium chloride 0. Day 15 VINBLASTINE** 6 mg/m2 iv infusion in 50 ml sodium chloride 0. Day 15 BLEOMYCIN* 10.9% over 10 minutes. 2 of 4 This is a controlled document and therefore must not be changed or photocopied ABVD Authorised by Lymphoma lead Published: September 2008 Version Dr. 6 and 8 courses as indicated. Discuss with consultant patients who are unwell / admission with neutropenic sepsis/platelets <50. modify as per trial protocol.Lymphoma group DRUG REGIMEN Each 4 week cycle consists of: Day 1 DOXORUBICIN 25 mg/m2 iv bolus.9% iv infusion over >1 hour.9% over 1-2 hours. DOSE MODIFICATIONS If patient is on clinical trial. PET-CT scan after two courses is currently NOT recommended outside the context of a clinical trial. Day 1 VINBLASTINE** 6 mg/m2 iv infusion in 50 ml sodium chloride 0. CYCLE FREQUENCY • • • • • • Each course is given every 28 days (ABVD is administered on Day 1 and Day 15).4 Date: August 2012 Amended: June 2011 May & Aug 2012 Review: June 2013 . Chris Hatton Reviewed: May 2010 3. Treatment should be delivered on time irrespective of the neutrophil count. RESTAGING • • • • Clinical assessment at least prior to each course and document in notes. give 50% dose reduction Doxorubicin maximum cumulative dose (additive to other anthracyclines): 450-550 mg/m2 (in normal cardiac function) 400 mg/m2 (in patients with cardiac dysfunction or exposed to mediastinal irradiation).000 units/m2 in 100 ml sodium chloride 0.9% over 10 minutes. Patients should not normally be supported with G-CSF. ** No 'ceiling' for vinblastine dosage in this protocol.9% iv infusion over >1 hour.9% over 1-2 hours. Maximum of 8 courses. NB: * Maximum of 6 courses (12 doses) of bleomycin may be given. Doxorubicin: Renal impairment Discuss with consultant if renal impairment severe Hepatic impairment Bilirubin micromol/L Dose 20-51 50% dose reduction 51-85 75% dose reduction >85 omit If AST 2-3 x normal. Day 1 DACARBAZINE 375 mg/m2 iv infusion in 250-500 ml sodium chloride 0. Consider dose reduction in the event of cardiac impairment. wait 6 – 8 weeks after last course.

Allopurinol 300 mg daily. Day 1: Fluconazole 50 mg od continuous. no validated recommendations on dose reductions can be given currently (SPC).4 Date: August 2012 Amended: June 2011 May & Aug 2012 Review: June 2013 .refer to Bleomycin supportive care document. 15-16: High.Lymphoma group Bleomycin: Renal impairment Hepatic impairment CrCl >50 ml/min 100% dose Clinical decision CrCl 10-50 ml/min 25% dose reduction CrCl <10 ml/min 50% dose reduction Pulmonary Toxicity . Dacarbazine: Renal impairment . CONCURRENT MEDICATION If needed. EMETIC RISK Days 1-2. during treatment and for 3 months following. 3 of 4 This is a controlled document and therefore must not be changed or photocopied ABVD Authorised by Lymphoma lead Published: September 2008 Version Dr. starting on days 1 and 15. Aciclovir 200 mg tds for the duration of chemotherapy and for 3 months after completion. Vinblastine: Renal impairment Hepatic impairment Bilirubin 26-51 micromol/L or ALT/AST 60-180 u/L 50% dose reduction Bilirubin >51 micromol/L & normal ALT/AST 50% dose reduction Bilirubin >51 micromol/L & ALT/ AST >180 u/L omit Neuropathy . INVESTIGATIONS FBC.in the presence of motor weakness or severe sensory symptoms. to start 24 hours prior to chemotherapy and then continue for 7 days. a dose reduction is not usually required. Discuss with consultant. renal and liver profiles. Co-trimoxazole 480 mg od po on Mondays. elimination of dacarbazine is prolonged. In patients with combined renal and hepatic impairment. discuss reducing or withholding vinblastine with a consultant. Wednesdays and Fridays each week. Can be CrCl >60 ml/min give 100% dose hepatotoxic. Dexamethasone 8 mg prior to chemotherapy then Dexamethasone 4 mg BD for 4 doses to prevent toxicity from dacarbazine and bleomycin (include in TTO). CrCl 46-60 ml/min give 80% dose CrCl 30-45 ml/min give 75% dose CrCl <30 ml/min give 70% dose If there is mild to moderate renal or hepatic insufficiency alone.discuss with Hepatic impairment consultant BOPA recommendations: Activated and metabolised in the liver. However. Chris Hatton Reviewed: May 2010 3.

2. Pearcey RG. United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519).18(2):376-80. Anaphylaxis can occur very rarely following administration of Dacarbazine. Connors JM. Ortiz T. Miyata S. Doxorubicin may be stopped in future cycles if signs of cardiotoxicity. If bleomycin lung is suspected. ABVD is considered low risk for infertility. Boleti E. 2007 Feb. Ryder D. 4.21(4):607-14. Shustik C. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. Alteration in liver function tests and a transient rise in the LDH may occur.Lymphoma group ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS • Reactions to bleomycin are common and may present with shortness of breath. J Clin Oncol. Tallman MS. PFTs. 2012 Feb 2. Glick JH. Stenning SP. Duggan DB. 2003 Feb 15. Winter JN.updated January 2009). Jack AS. Bennett CL. 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 (ISRCTN97144519). J Clin Oncol. 2005 Dec 20. The presentation may mimic the underlying present condition. Meyer RM. Djurfeldt MS. Ann Oncol. Cilley J. Eastern Cooperative Oncology Group. Mead GM.23(36):9208-18. Fisher RI.Dosage Adjustment for Cytotoxics in Hepatic Impairment (Version 3 .updated January 2009). Br J Haematol. Shepherd LE. e. Wells WA. 2007 Jun. Variakojis D. UCLH . Hancock BW. 4 of 4 This is a controlled document and therefore must not be changed or photocopied ABVD Authorised by Lymphoma lead Published: September 2008 Version Dr. Catsaros K. Winter JN. 6. Cardiotoxicity . Photosensitivity reactions may occur rarely. Johnson JL. Chen BE. NCIC Clinical Trials Group. UCLH . Rademaker A. Connors JM. Cullen MH. Hou N. Walewski J. MacLennan KA. tachycardia with fatigue. Clawson S. Radford JA. G-CSF is not necessary to maintain over 99% dose-intensity with ABVD in the treatment of Hodgkin lymphoma: low toxicity and excellent outcomes in a 10-year analysis. Augustyniak C. Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial. Horning SJ. Smith P. Gounder M. N Engl J Med.137(6):545-52. Canellos GP. Gospodarowicz MK. cardiac arrhythmias. Evens AM. 5. Crump M. 3. 7.g. Chris Hatton Reviewed: May 2010 3. ABVD for Hodgkin's lymphoma: full-dose chemotherapy without dose reductions or growth factors. Petroni GR. Johnson PW.4 Date: August 2012 Amended: June 2011 May & Aug 2012 Review: June 2013 .Dosage Adjustment for Cytotoxics in Renal Impairment (Version 3 .366(5):399-408. • • • • REFERENCES 1. Consider use of antibiotics and systemic steroids (see bleomycin supportive care policy). Sydes MR. Peterson BA. Stewart DA. pericardial effusion. high resolution CT scanning of the chest.monitor cardiac function. cough or 'flu like' symptoms. Gordon LI. Dar AR. measurement of arterial O2 saturation should be performed and the bleomycin discontinued.