A phase I trial of oxaliplatin and topotecan in recurrent ovarian carcinoma.
OBJECTIVE
Oxaliplatin and topotecan have demonstrated activity as single agents against recurrent platinum-sensitive and -resistant ovarian cancer, as well as synergy in vitro. This was a dose-finding study of combination therapy with weekly topotecan and alternating-week oxaliplatin in patients with recurrent epithelial ovarian cancer.


METHODS
Eligible patients had a diagnosis of recurrent ovarian or primary peritoneal carcinoma, a performance status of 0-2, and normal bone marrow, renal, and hepatic function. On days 1 and 15 of a 28-day cycle, patients received a fixed dose of oxaliplatin (85 mg/m2) via intravenous infusion. On days 1, 8, and 15, patients received an escalating dose of intravenous topotecan (2.0-4.0 mg/m2). Five dose levels were planned with a minimum cohort of 3 patients at each level.


RESULTS
Thirteen patients were enrolled and received a total of 50 cycles of chemotherapy. The maximum tolerated dose was 85 mg/m2 of oxaliplatin and 3.0 mg/m2 of topotecan, and grade 3 neutropenia was the dose-limiting toxicity. Four of nine (44%) evaluable patients had stable disease or a partial response to the drug combination as assessed by cancer antigen-125 levels.


CONCLUSIONS
A 28-day schedule of oxaliplatin and topotecan is safe and well tolerated. Because of the in vitro synergy observed between topoisomerase I inhibitors and platinum derivatives and the tolerability reported in the current study, this regimen warrants further investigation.
Elkas
John C
JC
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Walter Reed Army Medical Center, Washington, DC, USA. jelkas@nvpsa.net
Winter
William E
WE
Chernofsky
Mildred R
MR
Sunde
Jan
J
Bidus
Michael A
MA
Bernstein
Sarah
S
Rose
G Scott
GS
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077150:Oxaliplatin; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D019772:Topotecan