INTEGRATION OF FILGRASTIM INTO CHEMORADIATION FOR LIMITED SMALL-CELL LUNG-CANCER - A PHASE-I STUDY

Purpose: Recent studies document the value of early combined modality therapy of small cell lung cancer, but also indicate that early thorac ic radiation adds to myelosuppression and can complicate further chemo therapy, Other studies indicate that simultaneous use of growth factor s with thoracic radiation may be deleterious, However, temporal separa tion of growth factor use from cytotoxic therapy may allow dose intens ity to be maintained/enhanced during combined modality treatment. We s ought to integrate filgrastim into a novel chemoradiation regimen for patients with limited small cell lung cancer using an approach that se parated growth factor administration from both chemotherapy and thorac ic radiation, Methods and Materials: Twenty-seven patients with limite d disease small cell lung cancer were enrolled in a Phase I trial of c isplatin, ifosfamide/mesna, oral etoposide, and thoracic radiation (1. 5 Gy b.i.d. x 30 fractions days 1-19 cycle 1) +/- filgrastim (5 mu gf/ kg/day). Filgrastim was given on days 20-25 of cycle 1 after completio n of radiation and following completion of oral etoposide in subsequen t cycles, The primary end point was determination of maximum tolerated dose (MTD) of chemotherapy, Serial cohorts were treated with and with out filgrastim, Results: Because of dose-limiting thrombocytopenia, pr imarily, and nonhematologic toxicity, the MTDs with and without filgra stim were identical (cisplatin 20 mg/m(2) i.v. and ifosfamide 1200 mg/ m(2) i.v., both given days 1-3, and etoposide 40 mg/m(2) p.o. days 1-1 4), Filgrastim use shortened the duration of neutropenia at the MTD (m edian 4 vs. 7 days), but was not associated with a reduction in febril e neutropenia, Although growth factor administration did not allow dos e escalation of this regimen, it did allow chemotherapy doses to be ma intained at the MTD more frequently through four cycles of therapy, In the 24 evaluable patients, the overall response rate was 100% (71% pa rtial and 29% complete), Conclusions: Despite careful attention to the timing of growth factor with chemoradiation, the administration of fi lgrastim with this regimen did not allow dose escalation. As in many o ther recent studies of hematopoietic growth factors given prophylactic ally with chemotherapy, the duration of neutropenia at the MTD was sho rtened and the need for dose reduction throughout treatment was reduce d in patients receiving filgrastim at the MTD. (C) 1998 Elsevier Scien ce Inc.