DOSE-ESCALATION OF PACLITAXEL WITH HIGH-DOSE CYCLOPHOSPHAMIDE, WITH ANALYSIS OF PROGENITOR-CELL MOBILIZATION AND HEMATOLOGIC SUPPORT OF ADVANCED OVARIAN-CANCER PATIENTS RECEIVING RAPIDLY SEQUENCED HIGH-DOSE CARBOPLATIN CYCLOPHOSPHAMIDE COURSES

Purpose: We commenced a phase I study of escalating-dose (paclitaxel; Bristol-Myers Squibb Co, Wallingford, CT) in addition to cyclophospham ide, to assess its impact on both antitumor efficacy and mobilization of peripheral-blood progenitor cells (PBP). Patients and Methods: Indu ction therapy consisted of two cycles of cyclophosphamide 3.0 g/m(2) p lus escalating-dose Taxol (dose levels I to IV, 150, 200, 250, and 300 mg/m(2), respectively) in cohorts of three, plus filgrastim granulocy te colony-stimulating factor [G-CSF]) and leukaphereses to harvest PBP , followed by four courses of rapidly cycled carboplatin and cyclophos phamide (1,000 and 1,500 mg/m(2) per course, respectively), for which hematopoietic rescue was achieved with PBP. Results: Sixteen patients completed all planned cycles of Toxol/cyclophosphamide. Fifty-four cyc les of carboplatin/cyclophosphamide were given and rescued with PBP. T he median interval between treatments for Taxol/cyclophosphamide cours es was 14 days (range, 13 to 21). Twelve patients completed all planne d cycles of carboplatin/cyclophosphamide. The median inter-treatment i nterval for carboplatin/cyclosphoshamide courses when rescue was achie ved with Taxol/cyclophosphamide-primed PBP wets 17 days (range, 14 to 25). The median number of days to recovery of an absolute neutrophil c ount (ANC) greater than 0.5 was 8 (range, 5 to 12), and of self-sustai ning platelet count greater than 20 x 10(9)/L, 11 (range, 8 to 15). Th ere was one episode of fatal sepsis. Of 13 patients assessable for res ponse, there were five patients with pathologic complete responses (38 .5%), six patients with microscopic residual disease (46%), and two pa tients with pathologic partial responses, for an overall response rate of 100%. Conclusion: The addition of escalating-dose Taxol to high-do se cyclophosphamide does not compromise PBP mobilization. The use of P BP mobilized in this fashion provides reliable engraftment after seque ntial administration of high-dose carboplatin/cyclophosphamide. Toxici ties produced with this approach are manageable. The response rates de monstrated are promising and warrant further evaluation. (C) 1995 by A merican Society of Clinical Oncology.