BEXXAR also seems to show promise in front-line improving CHOP therapy.
[3504] A Phase II Trial of CHOP Followed by Bexxar™ (Tositumomab and Iodine-131-Tositumomab) for Treatment of Newly Diagnosed Follicular Non-Hodgkin’s Lymphomas (SWOG 9911).
Oliver W. Press, Joseph M. Unger, Rita M. Braziel, David G. Maloney, Michael L. LeBlanc, Thomas M. Grogan, Thomas P. Miller, Richard I. Fisher. Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Statistical Center, Southwest Oncology Group, Seattle, WA, USA; Pathology, Oregon Health Sciences University, Portland, OR, USA; Arizona Cancer Center, University of Arizona, Tuscon, AZ, USA; Wilmot Cancer Center, University of Rochester, Rochester, NY, USA
Advanced follicular lymphomas are incurable with conventional chemotherapy regimens. The Southwest Oncology Group investigated the safety and efficacy of a novel treatment approach by administering 6 cycles of standard CHOP chemotherapy (cyclophosphamide 750 mg/m2 , doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 , and prednisone 100 mg po for 5 days) given at 3 week intervals followed by radioimmunotherapy. Four weeks after the completion of the last cycle of CHOP, patients with a partial (PR) or complete remission (CR) to chemotherapy underwent dosimetry with 450 mg of unlabeled tositumomab (anti-CD20) antibody and 35 mg of trace-labeled Iodine-131-tositumomab (Bexxar®). Based on the rate of clearance of this dosimetric infusion from the body as assesed by gamma counting, subjects were treated with Bexxar labeled with 48-115 mCi of I-131 (median 84 mCi), estimated to deliver 75 cGy to the whole body (or 65 cGy if the platelet count was 100,000-149,999). This therapeutic dose was administered 1-2 weeks after the trace-labeled dose. 102 patients with newly-diagnosed follicular lymphomas (grade 1, 2, or 3) were registered by the time of study closure on June 1, 2000 and 92 were eligible. 88 patients are currently evaluable for toxicity from the CHOP regimen and 33 (38%) experienced grade 4 toxicities with CHOP, including 31 (35%) with grade 4 hematologic toxicities. Sixty patients are evaluable at the current time for toxicities from I-131-tositumomab and 8 patients (13%) had 10 grade 4 toxicities including 4 with neutropenia, 2 with leukopenia, 2 with thrombocytopenia, one with an anaphyllactoid reaction and one with chest and back pain. There were no treatment-related deaths. Seventy-one of the currently analyzable patients have been evaluated for response to the combination of CHOP + I-131-tositumomab and 51 (80%) have achieved an objective remission, including 37 confirmed or unconfirmed CRs (52%) and 20 PRs (28%). One patient (1%) had progressive disease on therapy, two patients (3%) had stable disease, and 11 patients (15%) did not have sufficient data available to assess response. In 17 patients (24%), the addition of I-131-tositumomab to CHOP improved the overall best response, either from a partial to a complete response (15 patients, 21%) or from an unconfirmed to a confirmed complete response (2 patients, 3%). Serial molecular monitoring of the t(14;18) translocation in the blood and bone marrow was performed by polymerase chain reaction at study entry, after completion of 6 cycles of CHOP, and 72 days, 6 months and 12 months following I-131-tositumomab. (The PCR analysis is currently pending). We conclude that the addition of I-131-tositumomab radioimmunotherapy to 6 cycles of CHOP chemotherapy is feasible, well-tolerated, and efficacious. SWOG has recently initiated a three armed, prospective randomized study (SWOG 0016) to compare this CHOP + Bexxar® regimen to CHOP alone and to CHOP + rituximab.
Keywords: Antibody\ Tositumomab\ Follicular lymphoma |
