title: Randomized phase II study of daily versus continuous-infusion schedules of topotecan in the treatment of extensive-stage small cell lung cancers.
abstract: A randomized two-stage, phase II study was conducted to assess the antitumor activity of two different schedules of topotecan in the treatment of extensive-stage small-cell lung cancer (SCLC) in chemotherapy-naive patients. A total of 40 eligible patients were randomized to receive either the daily schedule, with topotecan being administered intravenously at 1.5 mg/m2 daily for 5 days every 3 weeks, or the continuous-infusion schedule, with topotecan administered intravenously at a dosage of 1.3 mg/m2 per day over 72 hours every 4 weeks. Randomization to the continuous-infusion schedule was discontinued due to inactivity, and an additional 20 patients were treated on the daily schedule. Patients received an average of 5 courses (range: 1-13) of the daily schedule compared to an average of 2 courses (range: 1-7) of the continuous-infusion schedule (p < 0.01). Confirmed response rates for the daily and continuous-infusion schedules are 62.5% (90% CI: 49-75%) and 15% (90% CI: 1-29%), respectively. Toxicity was predominantly hematologic with 92% (55/60) having greater than or equal to grade III neutropenia and 58% (35/60) reporting greater than or equal to grade III leukopenia for both IV schedules. Nonhematologic toxicity was very mild, with only 10% (6/60) patients experiencing grade IV toxicities. One patient died of infection on the continuous-infusion arm. Median times to progression for the daily and continuous-infusion schedules are 5 months (90% CI: 4.4-7.2) and 2 months (90% CI: 1.1-2.1), respectively. Estimated 1-year survival rates for patients receiving daily and continuous-infusion schedules are 63% (90% CI: 51-76%) and 55% (90% CI: 39-77%), respectively. Fifty percent (30/60) of patients received second-line therapy with etoposide and cisplatin. Forty-three percent (13/30) of patients who received second-line therapy achieved a confirmed response. Topotecan showed significant activity in the treatment of extensive stage SCLC when administered as a brief daily IV repeated every 3 weeks.
authors.affiliation: Toledo Community Hospital Oncology Program CCOP, Toledo, Ohio, USA.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Schaefer
authors.forename: Randolph S
authors.initials: RS
authors.lastname: Marks
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Mahoney
authors.forename: Jeff A
authors.initials: JA
authors.lastname: Sloan
authors.forename: Mitchell D
authors.initials: MD
authors.lastname: Bauman
authors.forename: Henry D
authors.initials: HD
authors.lastname: Tazelaar
authors.forename: John W
authors.initials: JW
authors.lastname: Kugler
authors.forename: James A
authors.initials: JA
authors.lastname: Mailliard
authors.forename: Larry P
authors.initials: LP
authors.lastname: Ebbert
authors.forename: Martin
authors.initials: M
authors.lastname: Wiesenfeld
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D019772:Topotecan / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D005047:Etoposide; D019772:Topotecan; D002945:Cisplatin