Phase 2 trial of carboplatin plus tamoxifen in platinum-resistant ovarian cancer and primary carcinoma of the peritoneum.
OBJECTIVE
A previously reported phase 2 trial suggested substantial clinical activity associated with the combination of a platinum agent and tamoxifen in the treatment of platinum-resistant ovarian cancer. We wished to confirm or refute this observation in a patient population with well-characterized platinum-resistant disease.


METHODS
Patients with ovarian or fallopian tube cancers or primary carcinoma of the peritoneum whose disease had either failed to respond to a platinum-based regimen or had responded but experienced a "treatment-free interval (TFI)" of < or =3 months, or if the TFI was >3 months they had been retreated and failed a platinum-based program, were eligible for entry into this phase 2 single institution protocol. Carboplatin (AUC 5) was delivered on a q-21 day cycle. Tamoxifen was administered at a dose of 80 mg/day for the first cycle, and then reduced to 40 mg/day. Treatment was to be continued until evidence of disease progression or unacceptable toxicity.


RESULTS
Fourteen patients were treated on this phase 2 trial. In addition to being platinum-resistant, 10 patients had cancers that were also documented to be taxane-resistant (similar criteria to that defined above for platinum). While treatment was generally well tolerated, there were no objective (measurable disease or CA-125 response criteria) or subjective responses to this treatment program.


CONCLUSIONS
In this phase 2 trial, we have been unable to confirm a meaningful level of clinical activity for the combination of carboplatin plus tamoxifen in a patient population with well-characterized platinum-resistant ovarian cancer.
Department of Hematology/Medical Oncology, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. markman@ccf.org
Maurie
M
Markman
Kenneth
K
Webster
Kristine
K
Zanotti
Gertrude
G
Peterson
Barbara
B
Kulp
Jerome
J
Belinson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects
D013629:Tamoxifen; D016190:Carboplatin; D002945:Cisplatin