Abstract
The major challenge in treatment of early stage HL has been to achieve excellent treatment results while reducing short and long-term toxicities. Radiation therapy (RT) is a major cause of long-term toxicity. Doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) is the established standard chemotherapy regimen for HL. Treatment results in early stage HL with ABVD alone are similar to those with ABVD + RT. Bleomycin pulmonary toxicity is the major cause of short-term morbidity and mortality. Gemcitabine is one of the most active single agents for relapsed/refractory HL with response rates 39–43%, and promising results have been reported in CALGB 59804 in relapsed HL with gemcitabine, vinorelbine and liposomal doxorubicin (
Ann Oncol 18: 1071–9, 2007
). For these reasons, CALGB conducted a phase II trial of AVG for the initial treatment of stages I and II non-bulky HL. Treatment consisted of doxorubicin 25 mg/m2, vinblastine 6 mg/m2 and gemcitabine 800mg/m2 every 2 weeks for 12 treatments (6 cycles). By study design the dose of gemcitabine was decreased from 1000 mg/m2 to 800 mg/m2 because of at least grade 3 neutropenia in the first 5/6 patients. Growth factor support was permitted following a dose delay due to neutropenia. Responses were assessed according to the International Workshop criteria (JCO 17: 1244–53, 1999
). Positron emission tomography (PET) was performed prior to treatment, after 2 and after 6 cycles of AVG. Results were centrally read by 2 independent reviewers and an adjudicator. PET results were not employed in remission assessment. The primary endpoint was complete response rate (CR) + CR/unconfirmed (u). Based on published results with ABVD, the null hypothesis was CR rate ≤ 85% vs. the alternative ≥ 92%. At least 88/98 patients had to achieve CR + CRu for AVG to be considered promising. 104 patients were enrolled, 5 never began treatment. Thus, 99 patients were assessable: median age 38 years (18–80), stages: 10 IA, 70 IIA, 19 IIB. 34/99 (34.3%) patients were ≥45 years of age. 91 patients completed 6 cycles of treatment. CR + CRu: 67/99 (67.7%) (95% CI; 58–77%), partial response (PR): 27/99 (27.3%), stable 4/99 (4%), not assessable 1/99 (1%). 17 patients have relapsed: 9 CR + CRu, 6 PR, 2 stable. Median followup for patients who did not relapse is 1.1 years (0.1 – 2.5). The estimated 1 and 2 year progression free survivals (95% CI) are 0.81 (0.70, 0.89) and 0.71 (0.54, 0.83). All patients are alive. Less than 10% of patients experienced grade 3 or 4 toxicities with the exception of leukopenia and neutropenia. Of the 93 patients who received the 800 mg/m2 dose of gemcitabine, 74% had grade 3 and 28% grade 4 neutropenia. The CR + CRu rates for AVG were lower and the early PFS was shorter than expected. Correlations of month 2 and month 6 PET results with response and PFS will be reported.
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