EFFICACY OF LENOGRASTIM ON HEMATOLOGIC TOLERANCE TO MAID CHEMOTHERAPYIN PATIENTS WITH ADVANCED SOFT-TISSUE SARCOMA AND CONSEQUENCES ON TREATMENT DOSE-INTENSITY

This two-arm, double-blind, randomized ducted to determine the effects of lenograstim, a glycosylated recombinant human granulocyte colony-s timulating factor (rHU-G-CSF), on the hematologic tolerance of patient s with sarcoma treated with mesna, doxorubicin, ifosfamide, and doxoru bicin (MAID) chemotherapy. Patients and Methods: Forty-eight patients with metastatic or locally advanced soft tissue sarcoma were, followin g the first cycle of a combination with doxorubicin 60 mg/m(2), ifosfa mide 7.5 g/m(2), and dacarbazine 900 mg/m(2) given on days 1 to 3, ran domized to receive either lenograstim 5 mu g/kg/d by once-daily inject ion from day 4 to day 13, or its vehicle. For subsequent cycles, 28 pa tients continued on the same chemotherapy and lenograstim was systemat ically given as prophylactic treatment in an open manner. Results: Fol lowing the first cycle of MAID, the duration of neutropenia was reduce d in patients who received lenograstim as compared with those who rece ived placebo, with a median duration of neutropenia (< 0.5 x 10(9)/L n eutrophils) of 0 days (range, 0 to 3) and 5 days (range, 0 to 10), res pectively (P < .001). All patients who received lenograstim had recove red at least 1 x 10(9)/L Purpose: trial was con neutrophils (polymorph onuclear lymphocytes [PMN]) on day 14, compared with only one of 26 in the placebo group (P < .001). The median time to recover this neutrop hil level was 12 days (range, 10 to 13) and 17 days (range, 14 to 21), respectively (P < .001). Neutropenic fever occurred in five (23%) and 15 (58%) patients, respectively (P = .02). Twenty-eight patients rece ived at least two cycles (median, four) of MAID at the same dose. Toxi city remained constant across all treatment cycles. A progressive incr ease in thrombocytopenia was noted, with median platelet nadirs of 102 x 10(9)/L at cycle 2 and 19.5 x 10(9)/L at cycle 6, but did not resul t in significant treatment modifications. Consequently, median relativ e dose-intensities remained greater than 0.95 for up to six consecutiv e MAID cycles. Conclusion: Lenograstim significantly improved hematolo gic tolerance in patients treated with the MAID chemotherapy regimen a nd, therefore, allowed optimal adhesion to the theoretic doses planned for up to six cycles. Whether such an optimization in relative dose-i ntensity will result in an improvement of treatment efficacy remains t o be determined. (C) 1995 by American Society of Clinical Oncology.