Phase I feasibility trial of carboplatin, paclitaxel, and gemcitabine in patients with previously untreated epithelial ovarian or primary peritoneal cancer: a Gynecologic Oncology Group study.
OBJECTIVE
To determine the feasibility of administering a minimum of four cycles of carboplatin, paclitaxel, and gemcitabine (CPG) every 21 days without excessive dose modification or cycle delay in patients with previously untreated epithelial ovarian cancer or primary peritoneal cancer.


METHODS
Paclitaxel 175 mg/m(2) was given over 3 h followed by carboplatin concentration time curve (AUC) 5 (day 1) and gemcitabine 1 g/m(2) (days 1 and 8) in the first cohort. A second cohort received paclitaxel 135 mg/m(2) over 3 h followed by carboplatin AUC 5 (day 1) and gemcitabine 800 mg/m(2) (days 1 and 8). A maximum of eight cycles was administered.


RESULTS
Fourteen patients received 89 cycles during the first cohort. Seven patients experienced 19 hematologic dose-limiting events (DLEs) within the first four cycles, including grade 4 thrombocytopenia (n = 9), febrile neutropenia (n = 3), and omission of gemcitabine on day 8 (n = 7). This exceeded the threshold for nonfeasibility. In the second, less intense regimen, 36 patients were entered. Thirty-one evaluable patients received a total of 200 and median of 6 (range: 2-8) cycles. Thirteen of the thirty-one had 27 DLEs within the first four cycles including grade 4 thrombocytopenia (n = 5), prolonged grade 4 neutropenia (n = 2), febrile neutropenia (n = 2), and omission of day 8 gemcitabine (n = 18). There was one patient death secondary to a wound abscess and febrile neutropenia. Myelosuppression as expected was the dose-limiting toxicity.


CONCLUSIONS
The schedule of paclitaxel 135 mg/m(2) (day 1, 3 h), carboplatin AUC 5 (day 1), and gemcitabine 800 mg/m(2) (days 1 and 8) is feasible, with an acceptable toxicity profile.
Look
Katherine Y
KY
Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. klook@iupui.edu
Bookman
Michael A
MA
Schol
Jessie
J
Herzog
Thomas J
TJ
Rocereto
Thomas
T
Vinters
Jennifer
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine