title: A pilot study of topotecan in the treatment of serous carcinoma of the uterus.
abstract: A pilot study investigated topotecan (Hycamtin, GlaxoSmithKline, Philadelphia, PA), a topoisomerase I inhibitor, in treating uterine serous carcinoma, a typically unresponsive aggressive tumor. Fifteen patients were surgically staged, then treated with topotecan (1.5 mg/m2, Days 1-5 every 21 days) as first-line therapy (n = 12) or secondary to platinum failure (n = 3). Patients received topotecan through six courses, disease progression, or unacceptable toxicity. Grade 3/4 hematologic toxicity prompted dose adjustments. Thirteen patients exhibited no gross evidence of residual disease postoperatively. At topotecan initiation, one patient had 5-cm and one had < 1-cm residual disease. Seventy-eight courses (median, six) were administered; 12 (80%) patients completed the specified protocol. Common serious toxicities included grade 3 neutropenia (33%), anemia (13%), and thrombocytopenia (13%). Eight patients received erythropoietin and/or granulocyte colony-stimulating factor. Median follow-up for 14 evaluable patients was 26 months (range, 13-40). Of 11 evaluable first-line topotecan patients, nine were alive at follow-up; five were disease-free. Of three second-line topotecan patients, two died and one was alive with disease 31 months post-treatment. One patient with measurable disease achieved a complete and one a partial response as assessed by computed tomography scan. Median progression-free survival was 25 months; median survival has not been reached at 26 months. Although topotecan's antitumor activity cannot yet be quantified, disease-free interval and survival outcomes compare favorably with other therapies in uterine serous carcinoma. Further evaluation of topotecan in this population is warranted.
authors.affiliation: Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut, USA. Joseph_Chambers@chpmet.org
authors.forename: J T
authors.initials: JT
authors.lastname: Chambers
authors.forename: T J
authors.initials: TJ
authors.lastname: Rutherford
authors.forename: P E
authors.initials: PE
authors.lastname: Schwartz
authors.forename: M L
authors.initials: ML
authors.lastname: Carcangiu
authors.forename: S K
authors.initials: SK
authors.lastname: Chambers
authors.forename: L
authors.initials: L
authors.lastname: Baker
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018283:Cystadenocarcinoma, Papillary / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009519:New York City; D010865:Pilot Projects; D010984:Platinum; D016019:Survival Analysis; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery
chemical_list: D000970:Antineoplastic Agents; D010984:Platinum; D019772:Topotecan