title: Phase II study of the combination of pegylated liposomal doxorubicin and topotecan in platinum-resistant ovarian cancer.
abstract: The combination of liposomal doxorubicin and topotecan was evaluated in a phase II study in patients with platinum-resistant ovarian cancer. Twenty-seven patients received liposomal doxorubicin (30 mg/m(2)) infused at day 1, followed by topotecan (1 mg/m(2)) infusion daily for 5 days. Cycles were repeated every 21 days. This combination regimen showed an overall response rate of 28%. Median time to progression was 30 weeks, with a median overall survival of 40 weeks. Grade 3/4 neutropenia was shown in 70% of patients and grade 3/4 thrombopenia in 41% of patients. Neutropenic fever was reported in 11% of patients. After reviewing the first 12 patients, the internal review board decided to administer topotecan at a dose of 0.75 mg/m(2) and liposomal doxorubicin at 40 mg/m(2) for the remainder of the study. However, this adjustment did not lead to reduction in bone marrow toxicity nor to an improvement in dose intensity. Palmar-plantar erythrodysesthesia and mucositis were more reported in the second cohort but usually mild. The combination of liposomal doxorubicin and topotecan demonstrates favorable response data in platinum-resistant ovarian cancer. However, substantial bone marrow toxicity limits further clinical use.
authors.affiliation: Section of Medical Oncology and Section of Gynecology, UMC Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Verhaar-Langereis
authors.forename: A
authors.initials: A
authors.lastname: Karakus
authors.forename: M
authors.initials: M
authors.lastname: van Eijkeren
authors.forename: E
authors.initials: E
authors.lastname: Voest
authors.forename: E
authors.initials: E
authors.lastname: Witteveen
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008081:Liposomes; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D018570:Risk Assessment; D015996:Survival Rate; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D019772:Topotecan; D004317:Doxorubicin; D002945:Cisplatin