title: Protracted oral etoposide in epithelial ovarian cancer: a phase II study in patients with relapsed or platinum-resistant disease.
abstract: This phase II study evaluates the efficacy and toxicity of a prolonged schedule of oral etoposide in patients with measurable advanced ovarian cancer resistant to, or relapsed following, platinum-based chemotherapy. Forty-seven patients participated, 20 of whom had received more than one prior treatment. Seventy-seven per cent had evidence of disease progression during or within 6 months of the previous chemotherapy. Initially, oral etoposide, 50 mg b.d. (regardless of patient size), was given for 14 days on a 21-day cycle. However, after encountering toxicity, the schedule was modified to 7 days' treatment escalating to 10 then 14 days if well tolerated. Among 41 assessable patients there were two complete and eight partial objective responses (24% response rate; 95% confidence interval 12-41%). Nine further patients (22%) had stable disease, four with a sustained fall of > 50% in CA-125. Median duration of response or stable disease was 35 weeks (range 21-49). Overall median survival was 41 weeks from study entry (range 2 to 96+ weeks). Toxicity for most patients was mild, but sporadic severe myelotoxicity occurred, with two treatment-related deaths. Risk factors for severe toxicity were: performance status 3; hepatic impairment; renal impairment. We conclude that oral etoposide has activity in platinum-resistant ovarian cancer and that it is a useful palliative therapy. It has significant toxicity which may be avoided by appropriate patient selection and an escalating-duration schedule.
authors.affiliation: Department of Medical Oncology, St. Bartholomew's Hospital, London, UK.
authors.forename: M T
authors.initials: MT
authors.lastname: Seymour
authors.forename: J L
authors.initials: JL
authors.lastname: Mansi
authors.forename: C J
authors.initials: CJ
authors.lastname: Gallagher
authors.forename: M E
authors.initials: ME
authors.lastname: Gore
authors.forename: P G
authors.initials: PG
authors.lastname: Harper
authors.forename: T R
authors.initials: TR
authors.lastname: Evans
authors.forename: P M
authors.initials: PM
authors.lastname: Edmonds
authors.forename: M L
authors.initials: ML
authors.lastname: Slevin
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D016190:Carboplatin / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004848:Epithelium / Q000473:pathology; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011446:Prospective Studies
chemical_list: D005047:Etoposide; D016190:Carboplatin; D002945:Cisplatin