BACOP/FR combination chemotherapy as front-line treatment of follicular lymphoma. A phase II study of the Gruppo Italiano Studio Linfomi (GISL)

Abstract

7571 Background: Doxorubicin, fludarabine and rituximab are all considered active drugs in the treatment of follicular lymphoma (FL). Howevere, the best induction regimen is still matter of debate. In 2003 the GISL started a phase II trial to assess efficacy and tolerability of a combination of bleomycin, adriamycin, ciclophosphamide, vincristine and prednisone (BACOP) followed by fludarabine and rituximab (FR). Methods: To be included in the study pts should have: histologically confirmed diagnosis of FL, stage II-IV disease, age 18–70, active disease. Pts were assessed for t(14:18) by PCR on bone marrow at diagnosis and at time of response assessment. Treatment consisted in three courses of BACOP followed by 4 courses of FR for pts in partial remission (PR) or complete remission with persistent t(14:18) positivity (CRM+). Pts achieving molecular complete remission (CRM-) stopped therapy after BACOP. The main endpoints of the study were overall response rate (CR+PR) (ORR) and failure free survival (FFS). A final accrual of 60 assessable pts was planned, however a faster accrual than expected allowed to enrol 91 pts between May 2003 and Dec 2005. Results: At time of present analysis 61 pts were valuable for final response: Median age was 56 yrs (25–70), male gender 56%, 18% with systemic symptoms, 88% in stage III-IV disease, 13% had elevated LDH and 21% bulky disease. Molecular marker was present in 30 out of 57 pts. 19 pts achieved a CR after three courses of BACOP; four of them, being in CRM- stopped therapy. 28 pts achieved CR with four additional courses of FR. At the end of treatment CR and ORR were 77% and 90% respectively; relatively to pts with molecular marker at diagnosis CRM- was 60%. Toxicity data are available for 57 patients: grade III/IV anemia and neutropenia were observed in two (3%) and 18 (32%) cases respectively; severe infections occurred in two cases, both bacterial pneumonia. After a median follow-up of 17 months (0.5–31) 12 events were observed: Major toxicity, four; non responders, two; relapse, six. Conclusions: BACOP/FR is a feasible and safe regimen for the treatment of patients with FL with promising efficacy. More mature follow-up is required to confirm these preliminary results. No significant financial relationships to disclose.