Chemo/Rituximab Is Effective as First-Line CLL Therapy

LUGANO, Switzerland-The chemotherapy/immunotherapy regimen FCR (fludarabine, cyclophosphamide(Drug information on cyclophosphamide), rituximab(Drug information on rituximab)) has produced the highest complete response (CR) rate seen thus far in first-line treatment of chronic lymphocytic leukemia (CLL), according to investigator Michael J. Keating, MD. The FCR regimen, which is well tolerated, also results in molecular remissions in a "significant number" of complete responders, said Dr. Keating, professor of medicine, M.D. Anderson Cancer Center. "I think we now have an outpatient regimen that can accomplish PCR [polymerase chain reaction] negativity to a level that was formerly only achievable with various transplant procedures," Dr. Keating said. "It will be intriguing to follow these patients and see how durable these responses are." The study, which included 135 patients with CLL who received six cycles of FCR, achieved a complete response rate of 67% (90 patients), Dr. Keating reported at the 8th International Conference on Malignant Lymphoma (ICML abstract 008). By comparison, front-line fludarabine (Fludara), in previous investigations, has resulted in a 35% complete remission rate, while adding cyclophosphamide to fludarabine increases the CR rate to 43%. The FCR regimen is an infusion of rituximab (Rituxan) at a conventional dose (375 mg/m²) on the first day of the first cycle, with fludarabine and cyclophosphamide given on days 2, 3, and 4. In subsequent cycles, rituximab is given at a higher dose (500 mg/m²) on day 1, along with the 3-day fludarabine/cyclophosphamide couplet. Cycles are repeated every 4 weeks for a total of six cycles. The median patient age was 57 years, or somewhat lower than in previous studies of first-line treatment for CLL. Dr. Keating attributes this to the "Internet phenomenon"- younger patients seeking out more aggressive therapies. The treatment was well tolerated, with 74% of patients completing six cycles, and only 4% completing less than three cycles. Overall Response Rate
The overall response rate was 95%, including 67% complete remissions, 14% nodular partial remissions, and 14% partial remissions. Early death occurred in 2 patients (1%). "Although this is a very aggressive approach, the early death rate was actually quite low," Dr. Keating said. With a median follow- up of 27 months, 125 of the 135 patients are still alive. INDUSTRY WATCH
Phase II Trial of ISF154 for Treatment of CLL
SAN DIEGO-Tragen Pharmaceuticals has initiated a phase II clinical trial of its lead product, ISF154, in the treatment of patients with chronic lymphocytic leukemia (CLL). ISF154 is designed to activate dormant leukemia B-cells and rally T-cells to attack blood- and tissue-based leukemia cells, the company said in a press release. Investigators will administer ISF-154 to 40 patients in two cohorts: 20 patients who have failed chemotherapy will receive up to 10 doses of ISF154 over 20 weeks; 20 patients with advanced disease who have declined chemotherapy will receive up to 10 doses of ISF154 as frontline therapy. Complete response rate did not vary much according to Rai stage (69% for stage 0-II and 52% for stage III-IV). However, the CR rate was 66% for patients under 70 years of age vs 33% for patients over 70, and low beta-2-microglobulin levels were a "very powerful predictive factor" in favor of complete response. Molecular remission (as shown by PCR negativity for IgH) was seen in 58% of complete responders tested (33 of 57 patients). Of 26 patients tested again after 6 months, 18 (69%) remained negative, and 5 of 6 patients tested again at 12 months remained negative. Toxicity associated with rituximab infusion included fever and chills with the first dose for 45 patients; a few patients had hypotension, nausea, or dyspnea, although all of these toxicities were uncommon in later cycles. Hematologic toxicities included neutropenia (31% of cycles) and grade 3-4 thrombocytopenia (6% of cycles). Major infections occurred in 2% of cycles.