A phase II study of HCVIDDOXIL alternated with methotrexate-cytarabine in patients with newly diagnosed T-cell lymphoma.

7597 Background: T cell lymphomas (TCL) generally are more aggressive and have a poorer prognosis than the corresponding B cell lymphomas. A chemotherapeutic regimen that is effective in aggressive lymphoid malignancies is HCVAD alternating with methotrexate (MTX) and cytarabine (Ara-C). Pegylated liposomal doxorubicin (DOXIL) is associated with greater tumor penetration and less toxicity. We initiated a phase II study to evaluate the efficacy of the regimen HCVIDDOXIL, using DOXIL as a substitute for doxorubicin in the HCVAD regimen, alternated with MTX-Ara-C .,Previously untreated patients (pts) with Zubrod performance status ≤3, age > 18 years, and adequate organ function were eligible. Pts with skin involvement alone, CD30+, ALK +, T-anaplastic large cell lymphoma (ALCL), HIV-1 positive serology, and evidence of CNS involvement were excluded. Pts received HCVIDDOXIL ( cyclophosphamide 300 mg/m iv Q 12 h × 6 doses d 1-3, mesna 600 mg/m iv daily over 24 hours by continuous infusion d 1-3, DOXIL 25 mg/m/day iv on d 2, vincristine 1.4 mg/m (max. 2 mg) iv days 4 and 11, dexamethasone 40 mg iv or po daily × 4 d 1-4 and 11-14) alternated with MTX/Ara-C ( MTX 200 mg/m iv over 2 hours on d 1, then 800 mg/m iv over 22 hours on d1, Ara-C 3 g/m iv Q 12 hours × 4 doses on d 3-4) every 3 weeks for a maximum of 8 cycles. Endpoints were progression-free survival and response rate.,Between October 2003 and November 2005, 23 pts were enrolled. Median age 53 years (range, 23-68). Twelve pts had stage IV, 6 stage III, 3 stage I, and 2 stage II disease. Fourteen (60%) pts had extranodal disease, and 8 (36%) pts had an elevated LDH. In 21 evaluable pts, the ORR was 90% [CR n=12 (57%); PR n= 7 pts (33%)]. Common Grade 3-4 adverse events were thrombocytopenia in 17 pts (77%), neutropenia in 6 (27%), anemia in 5 (23%), and febrile neutropenia in 7 (32%). With a median follow-up of 13 months, the median progression-free survival is 8.3 months (95% CI: 6.5 to 14.2 months).,In this high-risk population the regimen HCVIDDOXIL alternated with MTX-Ara-C induced a high response rate. As expected, the most common toxicity was myelosuppression. The efficacy of this regimen should be confirmed in a larger cohort of patients. Enrollment in this study continues. No significant financial relationships to disclose.