Combination Chemotherapy in Treating Younger Patients With Hodgkin Lymphoma

Phase II Study Evaluating the Toxicity and Efficacy of a Modified German Paediatric Hodgkin's Lymphoma Protocol (HD95) in Young Adults (Aged 18-30 Years) With Hodgkin's Lymphoma

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known which regimen of combination chemotherapy is more effective for Hodgkin lymphoma. PURPOSE: This phase II trial is studying the side effects of three different regimens of combination chemotherapy and to see how well they work in treating younger patients with Hodgkin lymphoma.

OBJECTIVES: Primary To establish neurotoxicity of OEPA+COPP chemotherapy in young adults. Secondary To determine response rates in patients treated with this regimen. To determine disease-free survival of patients treated with this regimen. To determine overall survival of patients treated with this regimen. To determine gonadal toxicity in patients treated with this regimen. OUTLINE: Patients are assigned to treatment group according to stage. Group 1 (patients with stage 1A, 1B, or 2A disease): Patients receive OEPA chemotherapy comprising vincristine IV on days 1, 8, and 15; oral prednisolone on days 1-15; etoposide IV on days 1-5; and doxorubicin hydrochloride IV on days 1 and 15. Courses repeat every 28 days for 2 courses. Patients achieving a partial response also undergo radiotherapy after completion of chemotherapy; patients achieving a complete response do not undergo radiotherapy. Group 2 (patients with stage 2AE, 2B, or 3A disease): Patients receive 2 courses of OEPA chemotherapy as in group 1. Patients then receive COPP chemotherapy comprising cyclophosphamide IV on days 1 and 8; vincristine IV on days 1 and 8; oral procarbazine hydrochloride on days 1-15; and oral prednisolone on days 1-15. Courses repeat every 28 days for 2 courses. Patients also undergo radiotherapy after completion of chemotherapy. Group 3 (patients with stage 2BE, 3AE, 3BE, 3B, 4A, or 4B disease): Patients receive 2 courses of OEPA chemotherapy as in group 1. Patients then receive COPP chemotherapy as in group 2. Treatment with COPP chemotherapy repeats every 28 days for 4 courses. Patients also undergo radiotherapy after completion of chemotherapy. In all groups, treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically. Peer Reviewed and Funded or Endorsed by Cancer Research UK.

neurotoxicity, stage I adult Hodgkin lymphoma, stage II adult Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, adult lymphocyte depletion Hodgkin lymphoma, adult lymphocyte predominant Hodgkin lymphoma, adult mixed cellularity Hodgkin lymphoma, adult nodular sclerosis Hodgkin lymphoma

OEPA (28day cycle): Vincristine 1.5mg/m^2 iv d1,d8,d15 (capped at 2mg/dose) Etoposide 125mg/m^2 iv d1-5 Prednisolone 60mg/m^2 po d1-15 Adriamycin 40mg/m^2 iv d1 and 15

OEPA (28 day cycle) Vincristine 1.5mg/m^2 iv d1,d8,d15 (capped at 2mg/dose) Etoposide 125mg/m^2 iv d1-5 Prednisolone 60mg/m^2 po d1-15 Adriamycin 40mg/m^2 iv d1 and 15 COPP (28 day cycle) Cyclophosphamide 500mg/m^2 iv d1 and 8 Vincristine 1.5mg/m^2 iv d1,8 (capped 2mg/dose) Procarbazine 100mg/m^2 po d1-15* Prednisolone 40mg/m^2 po d1-15

OEPA (28 day cycle) Vincristine 1.5mg/m^2 iv d1,d8,d15 (capped at 2mg/dose) Etoposide 125mg/m^2 iv d1-5 Prednisolone 60mg/m^2 po d1-15 Adriamycin 40mg/m^2 iv d1 and 15 COPP (28 day cycle) Cyclophosphamide 500mg/m^2 iv d1 and 8 Vincristine 1.5mg/m^2 iv d1,8 (capped 2mg/dose) Procarbazine 100mg/m^2 po d1-15* Prednisolone 40mg/m^2 po d1-15

DISEASE CHARACTERISTICS: Biopsy proven de-novo classical Hodgkin lymphoma Any stage disease No nodular lymphocyte-predominant Hodgkin lymphoma PATIENT CHARACTERISTICS: No known or suspected HIV infection No pre-existing neurological disorder No serious comorbidity which may prevent administration of study treatment No other previous malignancy Not pregnant or nursing Fertile patients must use effective contraception during and for up to 1 year after completion of study treatment Creatinine ≤ 1.5 times upper limit of normal (ULN) unless due to the lymphoma ALT/AST ≤ 1.5 times ULN unless due to the lymphoma Bilirubin ≤ 2 times ULN unless due to the lymphoma PRIOR CONCURRENT THERAPY: No prior chemotherapy or radiotherapy No prior organ transplant