Preliminary Results of a Phase II Study of HCVIDDoxil Alternated with Methotrexate-Cytarabine in Patients with Newly Diagnosed T-Cell Lymphoma.

Background The prognosis of patients with T-cell lymphoma (TCL) remains poor with conventional chemotherapy regimens and innovative approaches are needed. We evaluated the efficacy and safety of the regimen HCVIDDoxil, with pegylated doxorubicin substituting doxorubicin in the HCVAD regimen, alternated with MTX-Ara-C in patients with newly diagnosed TCL.

Methods Previously untreated patients (pts) with Zubrod performance status 3 or less, age > 18 years, and adequate marrow, cardiac, liver and renal function were included in this study. Patients with ALK + anaplastic large cell lymphoma (ALCL), skin involvement alone, HIV positive serology, and evidence of CNS involvement were excluded. Patients received HCVIDDoxil (iv cyclophosphamide 300 mg/m² iv Q 12 h X 6 doses days 1–3, mesna 600 mg/m² iv daily over 24 hours by continuous infusion days 1–3, doxil 25 mg/m²/day iv on day 2, vincristine 1.4 mg/m² (max. 2 mg) iv days 4 and 11, dexamethasone 40 mg iv or po daily X 4 days 1–4 and 11–14) alternated with MTX/Ara-C (MTX 200 mg/m2 iv over 2 hours on day 1, then 800 mg/m² iv over 22 hours on day 1, Ara-C 3 g/m² iv Q 12 hours X 4 doses on days 3–4). Courses were repeated every 3 weeks for a maximum of 8 cycles. Endpoints were response rate and progression-free survival.

Results Between October 2003 and July 2007, 38 patients (pts) were included, 20 pts with PTCL, 6 pts with ALCL-ALK-, 4 pts with NK-TCL, 4 pts with HSL, and 4 pts with AIL. Median age was 54 (range, 23–70). Thirty-three (86%) pts had stage III/IV, 5 stage I/ II. Twenty-five (65%) pts had extranodal disease, and 14 (36%) pts had bone marrow involvement. A median of 5 cycles were delivered. To date 32 pts are evaluable for response. The ORR was 87%, with CR in 19 pts (59%) and PR in 9 pts (28%). Common Grade ¾ adverse events were thrombocytopenia in 31 pts (96%), neutropenia in 24 (75%), anemia in 23 (71%), and febrile neutropenia in 7 (32%). Six of the complete responders progressed (31%, median TTP 188 days), and 13 of the responses are ongoing (+6-+36 months).

Conclusions In this high-risk population the regimen HCVIDDoxil alternated with MTX-Ara-C induced a high response rate. Further follow-up is needed to evaluate if the high response rate results in improved disease-free survival. As expected, the major toxicity was myelosuppression. Enrollment in this study continues.