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Use of Hematopoietic Progenitors in Whole Blood to Support Dose-Dense Chemotherapy: A Randomized Phase II Trial in Small-Cell Lung Cancer Patients

From the Cancer Research Campaign Department of Clinical Oncology, City Hospital, Nottingham; Cancer Research Campaign Departments of Medical Oncology and Clinical Oncology, Christie Hospital, Manchester; and Amgen Ltd, Cambridge, United Kingdom.

Address reprint request to Penella J. Woll, MD, Cancer Research Campaign Department of Clinical Oncology, City Hospital, Hucknall Road, Nottingham NG5 1PB, United Kingdom; email: penella.woll@ nott.ac.uk.

PURPOSE: Small-cell lung cancer (SCLC) is exquisitely chemosensitive, but few patients are cured by conventional chemoradiotherapy. Recent studies suggest that increased cytotoxic dose-intensity might improve survival. In this randomized phase II study, we tested the feasibility of dose intensification 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. Intensified treatment was supported by daily subcutaneous filgrastim injections and reinfusion of 750 mL 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 treatment cycles, and 70% completed six cycles; 96% of treatments were given at full dose. The planned dose-intensity was 1.0 for standard and 2.0 for intensified ICE. The median received dose-intensity for cycles 1 through 3 was 0.99 (range, 0.33 to 1.02) for the standard treatment arm and 1.80 (range, 0.99 to 1.97) for the intensified treatment arm (P < .001). Over all six cycles, the median received dose-intensity was 0.95 (range, 0.17 to 1.03) for the 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 standard treatment arm (84% v 56%), resulting in more days of intravenous antibiotics (median, 10 v 3 days; P = .035). Transfusion requirements were similar in the two groups.

CONCLUSION: Sequential reinfusion of hematopoietic progenitors in whole blood can safely support substantial increases in dose-intensity of ICE chemotherapy for SCLC.

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