title: Prospective, multicenter, randomized, independent-group, open-label phase II study to investigate the efficacy and safety of three regimens with two doses of sagopilone as second-line therapy in patients with stage IIIB or IV non-small-cell lung cancer.
abstract: BACKGROUND
  Sagopilone is the first fully synthetic epothilone in clinical development and has proven preclinical activity in tumor models. This multicenter, randomized, open-label, phase II study examined the efficacy and safety of three regimens with two doses and two infusion durations of second-line sagopilone in pretreated patients with stage IIIB or IV non-small-cell lung cancer.
  
  
  METHODS
  Eligibility criteria included: at least one measurable lesion by modified response evaluation criteria in solid tumors; World Health Organization performance status of 0 or 1; and failure of previous platinum-based chemotherapy. Patients were randomized to receive: 16 mg/m2 sagopilone over 3 h (treatment arm A); 22 mg/m(2) sagopilone over 0.5 h (treatment arm B); or 22 mg/m2 sagopilone over 3h (treatment arm C). Treatment duration was two to six courses every 3 weeks; more than six treatment courses were permitted if there was sustained clinical benefit. The primary efficacy endpoint was best overall response after six courses; at least five confirmed responders per arm indicated a successful outcome.
  
  
  RESULTS
  In total, 128 patients (44, arm A; 41, arm B; 43, arm C) were randomized; 127 received at least one infusion of sagopilone. Baseline demographic data were similar across all arms. Eight patients across all arms had a confirmed partial response; the primary endpoint was not achieved. The most frequently reported adverse event (AE) was peripheral sensory neuropathy (75%). Most hematologic AEs were grade 1 or 2.
  
  
  CONCLUSIONS
  As fewer than five patients per arm responded after six treatment courses, the primary endpoint was not met. Sagopilone was only moderately tolerated. Most AEs, including peripheral neuropathy, were grade 1 or 2; hematologic toxicities were rare.
authors.affiliation: Lungen Clinic Grosshansdorf, Wöhrendamm 80, 22927 Grosshansdorf, Germany. d.heigener@lungenclinic.de
authors.forename: David F
authors.initials: DF
authors.lastname: Heigener
authors.forename: Joachim
authors.initials: J
authors.lastname: von Pawel
authors.forename: Corinna
authors.initials: C
authors.lastname: Eschbach
authors.forename: Andreas
authors.initials: A
authors.lastname: Brune
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmittel
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmelter
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
authors.forename: Jürgen R
authors.initials: JR
authors.lastname: Fischer
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D052160:Benzothiazoles / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D034261:Epothilones / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D052160:Benzothiazoles; D034261:Epothilones; C530494:sagopilone