Fixed-dose rate gemcitabine plus carboplatin in relapsed, platinum-sensitive ovarian cancer patients: results of a three-arm Phase I study.
OBJECTIVE
Standard infusion of gemcitabine plus carboplatin showed improved efficacy compared to carboplatin alone in patients with platinum-sensitive (Pt-S) ovarian cancer (OC). Fixed-dose rate (FDR) administration of gemcitabine produces more efficient intracellular phosphorylation of gemcitabine to its active form. This study was designed to identify the maximum tolerated dose (MTD), toxicity profile, and response rate of FDR gemcitabine plus carboplatin in Pt-S OC.


METHODS
Patients with measurable OC relapsing > or =6 months after exposure to platinum (N=60) were assigned to one of three treatment cohorts, each with a different delivery schedule and escalating doses of both FDR gemcitabine (10 mg/m(2)/min) and standard infusion carboplatin (60 min). MTDs were determined using dose-limiting toxicities (DLTs). Measurable disease was assessed using modified RECIST criteria. CA-125 levels were evaluated using Rustin criteria. Toxicities were assessed using NCI Common Toxicity Criteria, version 2.0.


RESULTS
The MTD of Arm 1 was FDR gemcitabine 1000 mg/m(2) on days 1 and 8 plus carboplatin AUC 5 on day 1, every 21 days. The MTD of Arm 2 was FDR gemcitabine 1000 mg/m(2) on days 1 and 8 plus carboplatin AUC 2.5+AUC 2.5 on days 1 and 8, every 21 days. Patient accrual on Arm 3 consisting of bi-weekly FDR gemcitabine plus carboplatin was terminated because dose level 1 exceeded the MTD. Overall response rates were 38.1% (Arm 1), 58.8% (Arm 2), and 44.4% (Arm 3).


CONCLUSIONS
FDR gemcitabine+carboplatin on a 21-day schedule was active and produced no unusual safety signals in patients with Pt-S OC.
Alvarez
Ronald D
RD
University of Alabama at Birmingham, Birmingham, AL 35294, USA. ronald.alvarez@ccc.uab.edu
Mannel
Robert
R
García
Agustin A
AA
Gallion
Holly H
HH
Lucci
Joseph
J
Kilgore
Larry C
LC
Numnum
Thomas M
TM
Zou
Sharon Xiaohan
SX
Orlando
Mauro
M
Tai
Datchen F
DF
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
D003841:Deoxycytidine; D016190:Carboplatin; D000093542:Gemcitabine