Dose escalation of paclitaxel with high-dose carboplatin using peripheral blood progenitor cell support in patients with advanced ovarian cancer.
A phase I study of escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given in combination with high-dose carboplatin was conducted to identify the antitumor efficacy and maximum tolerated dose of paclitaxel in patients who had received sequential cycles of paclitaxel/cyclophosphamide as prior treatment for ovarian carcinoma. Eighteen patients with advanced ovarian cancer were treated in this study. Induction therapy consisted of two cycles of cyclophosphamide 3.0 g/m2 plus high-dose paclitaxel 300 mg/m2 plus filgrastim and leukapheresis to harvest peripheral blood progenitor cells, followed by four courses of rapidly cycled high-dose carboplatin with planned dose escalation of paclitaxel (150, 200, 250, and 300 mg/m2) rescued with peripheral blood progenitor cells. The study was amended after accrual of 11 patients, and the remaining seven patients received a single cycle of induction therapy with paclitaxel/cyclophosphamide, followed by four courses of rapidly cycled high-dose carboplatin with planned dose escalation of paclitaxel through levels 200 and 250 mg/m2. All 18 patients have completed therapy. Of the 15 who are evaluable for response, the pathologic complete response was 33% (five of 15 patients). The administration of escalating doses of paclitaxel in combination with high-dose carboplatin following sequential cycles of paclitaxel/cyclophosphamide induction resulted in significant nonhematopoietic toxicity. Induction with a single cycle of paclitaxel/cyclophosphamide resulted in excellent progenitor cell mobilization, and significantly ameliorated the toxicity of this approach. The response rates thus far obtained are promising and warrant further evaluation.
Fennelly
D W
DW
Department of Medical and Gynecologic Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Aghajanian
C
C
Shapiro
F
F
O'Flaherty
C
C
O'Connor
K
K
Curtin
J P
JP
Crown
J P
JP
Hoskins
W J
WJ
Spriggs
D R
DR
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D003520:Cyclophosphamide; D004334:Drug Administration Schedule; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage*; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D016190:Carboplatin; D017239:Paclitaxel; D000069585:Filgrastim