title: A combination of platinum and tamoxifen in advanced ovarian cancer failing platinum-based chemotherapy: results of a Phase II study.
abstract: The treatment of recurrent or progressive ovarian cancer has limited therapeutic potential. The clinical outcome of second-line therapy largely depends on the potential chemo-sensitivity of the tumor expressed during up-front chemotherapy, as well as on the treatment-free interval from the last course of cytotoxic therapy. However, the identification of agents such as tamoxifen (TAM) at nontoxic doses, able to act synergistically with standard chemotherapy, may be useful to overcome resistance. Fifty patients with recurrent or progressive ovarian cancer following platinum (P)-based chemotherapy (28 platinum-resistant and 22 platinum-sensitive) entered a Phase II trial to evaluate the efficacy and toxicity of P re-challenge with the addition of TAM as a chemotherapy response modulator. The choice of the P compound (100 mg/m2 cisplatin or 400 mg/m2 carboplatin, q3 weeks) was made on the basis of the prior total cisplatin dose and the presence of neurotoxicity. TAM was administered at the doses of 80 mg/day for 30 days followed by 40 mg/day for the remaining period of treatment. Toxicity consisted mainly of mild to moderate nausea and vomiting (76%), peripheral neuropathy (43%), nephrotoxicity (4%), anemia (16%), leukopenia (58%) and thrombocytopenia (16%). The overall response to the P-TAM combination was 50% (complete response 30%; partial response 20%) with a median duration of 8.5 months (3-42). Sixty-four percent of the P-sensitive and 39% of the P-resistant patients responded (59% and 33%, respectively, for those bearing measurable disease). The overall median survival was 23 (3-48) and 19 months for the patients with measurable disease (20 months for the P-resistant group). This phase II trial confirmed the activity for a re-challenge employing a P compound and TAM in clinically defined P-resistant ovarian cancer patients. The mild toxicity profile and the relatively low cost of the treatment render further investigations on the P-TAM regimen worthwhile.
authors.affiliation: Department of Gynecology, Campus Biomedico Free University, Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Benedetti Panici
authors.forename: S
authors.initials: S
authors.lastname: Greggi
authors.forename: M
authors.initials: M
authors.lastname: Amoroso
authors.forename: G
authors.initials: G
authors.lastname: Scambia
authors.forename: F A
authors.initials: FA
authors.lastname: Battaglia
authors.forename: V
authors.initials: V
authors.lastname: Gebbia
authors.forename: G
authors.initials: G
authors.lastname: Salerno
authors.forename: M P
authors.initials: MP
authors.lastname: Paratore
authors.forename: S
authors.initials: S
authors.lastname: Mancuso
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D018269:Carcinoma, Endometrioid / Q000188:drug therapy / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects; D017211:Treatment Failure
chemical_list: D013629:Tamoxifen; D016190:Carboplatin; D002945:Cisplatin