Use of hematopoietic progenitors in whole blood to support dose-dense chemotherapy: A randomized phase II trial in small-cell lung cancer patients

Purpose: Small-cell lung cancer (SCLC) is exquisitely chemosensitive, but f ew patients are cured by conventional chemoradiotherapy. Recent studies sug gest that increased cytotoxic dose-intensity might improve survival. In thi s randomized phase II study, we tested the feasibility of dose intensificat ion using sequential reinfusion of hematopoietic progenitors in whole blood . Patients and Methods: SCLC patients with a favorable prognosis were treated with six cycles of ifosfamide, carboplatin, and etoposide (ICE), at 4-week (standard treatment) or 2-week (intensified treatment) intervals. Intensif ied treatment was supported by daily subcutaneous filgrastim injections and reinfusion of 750 mt of autologous blood collected immediately before each cycle. Results: Fifty consecutive patients were randomized to standard (n = 25) or intensified (n = 25) ICE. A total of 94% completed at least three treatmen t cycles, and 70% completed six cycles; 96% of treatments were given at ful l dose. The planned dose-intensity was 1.0 for standard and 2.0 for intensi fied ICE. The median received dose-intensity for cycles 1 through 3 was 0.9 9 (range, 0.33 to 1.02) for the standard treatment arm and 1.80 (range, 0.9 9 to 1.97) for the intensified treatment arm (P < .001). Over all six cycle s, the median received dose-intensity was 0.95 (range, 0.17 to 1.03) for th e standard treatment arm and 1.60 (range, 0.60 to 2.01) for the intensified treatment arm (P < .001). Febrile neutropenia was more common on the stand ard treatment arm (84% v 56%), resulting in more days of intravenous antibi otics (median, 10 v 3 days; P = .035). Transfusion requirements were simila r in the two groups. Conclusion: Sequential reinfusion of hematopoietic progenitors in whole blo od can safely support substantial increases in dose-intensity of ICE chemot herapy for SCLC. (C) 2001 by American Society of Clinical Oncology.