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

被引:53
作者
FENNELLY, D
SCHNEIDER, J
SPRIGGS, D
BENGALA, C
HAKES, T
REICH, L
BARAKAT, R
CURTIN, J
MOORE, MAS
HOSKINS, W
NORTON, L
CROWN, J
机构
[1] Mem. Sloan-Kettering Cancer Center, New York, NY
[2] Solid Tumor Division, Breast and Gynecol. Medicine Service, Mem. Sloan-Kettering Cancer Center, New York
关键词
D O I
10.1200/JCO.1995.13.5.1160
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: We commenced a phase I study of escalating-dose (paclitaxel; Bristol-Myers Squibb Co, Wallingford, CT) in addition to cyclophosphamide, to assess its impact on both antitumor efficacy and mobilization of peripheral-blood progenitor cells (PBP). Patients and Methods: Induction therapy consisted of two cycles of cyclophosphamide 3.0 g/m(2) plus escalating-dose Taxol (dose levels I to IV, 150, 200, 250, and 300 mg/m(2), respectively) in cohorts of three, plus filgrastim granulocyte colony-stimulating factor [G-CSF]) and leukaphereses to harvest PBP, followed by four courses of rapidly cycled carboplatin and cyclophosphamide (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 cycles of carboplatin/cyclophosphamide were given and rescued with PBP. The median interval between treatments for Taxol/cyclophosphamide courses was 14 days (range, 13 to 21). Twelve patients completed all planned cycles of carboplatin/cyclophosphamide. The median inter-treatment interval for carboplatin/cyclosphoshamide courses when rescue was achieved with Taxol/cyclophosphamide-primed PBP wets 17 days (range, 14 to 25). The median number of days to recovery of an absolute neutrophil count (ANC) greater than 0.5 was 8 (range, 5 to 12), and of self-sustaining platelet count greater than 20 x 10(9)/L, 11 (range, 8 to 15). There was one episode of fatal sepsis. Of 13 patients assessable for response, there were five patients with pathologic complete responses (38.5%), six patients with microscopic residual disease (46%), and two patients with pathologic partial responses, for an overall response rate of 100%. Conclusion: The addition of escalating-dose Taxol to high-dose cyclophosphamide does not compromise PBP mobilization. The use of PBP mobilized in this fashion provides reliable engraftment after sequential administration of high-dose carboplatin/cyclophosphamide. Toxicities produced with this approach are manageable. The response rates demonstrated are promising and warrant further evaluation. (C) 1995 by American Society of Clinical Oncology.
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页码:1160 / 1166
页数:7
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