title: Progression-free and overall survival in patients with relapsed/refractory germ cell tumors treated with single-agent chemotherapy: endpoints for clinical trial design.
abstract: BACKGROUND
  Refractory germ cell tumor (GCT) patients have a poor prognosis and limited treatment options. The identification of novel active agents may be impaired by use of response as the primary endpoint in phase 2 trials. Improved endpoints could enhance the development of new effective agents.
  
  
  METHODS
  The characteristics and outcome of refractory GCT patients enrolled in 7 single-agent phase 2 trials conducted at Memorial Sloan-Kettering Cancer Center from 1990 to 2008 were reviewed. The study agents were suramin, all-transretinoic acid, topotecan, pyrazoloacridine, temozolomide, ixabepilone, and sunitinib. The major endpoints evaluated were response, progression-free survival (PFS), and overall survival (OS).
  
  
  RESULTS
  Ninety patients (87 male, 3 female) were treated. The primary tumor site was testis in 65 patients, mediastinum in 17 patients, retroperitoneum in 4 patients, and other in 4 patients. Eighty-six patients had nonseminoma, and 4 patients had pure seminoma. Best responses were 1 (1%) partial response (ixabepilone), 15 (17%) stable disease, and 74 (82%) progressive disease. Median PFS and OS were 1.0 month (95% confidence interval [CI], 0.8-1.3) and 4.7 months (95% CI, 3.5-6.4), respectively. Eighty-six of the 90 patients have died. The 12- and 16-week PFS rates were 9% (95% CI, 3-15%) and 6% (95% CI, 1%-11%), respectively.
  
  
  CONCLUSIONS
  Patients with refractory GCT progressed rapidly to these single agents. PFS and OS may be useful endpoints for designing phase 2 trials testing novel agents in this population. Twelve-week PFS (with comparison to the 9% benchmark rate reported herein) is the recommended endpoint for phase 2 trial design and median OS (using 4.7 months as the predicted median for the control arm) is suggested for phase 3 trials.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. feldmand@mskcc.org
authors.forename: Darren R
authors.initials: DR
authors.lastname: Feldman
authors.forename: Sujata
authors.initials: S
authors.lastname: Patil
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Trinos
authors.forename: Maryann
authors.initials: M
authors.lastname: Carousso
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Ginsberg
authors.forename: Joel
authors.initials: J
authors.lastname: Sheinfeld
authors.forename: Dean F
authors.initials: DF
authors.lastname: Bajorin
authors.forename: George J
authors.initials: GJ
authors.lastname: Bosl
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D008479:Mediastinal Neoplasms / Q000188:drug therapy / Q000401:mortality; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000401:mortality*; D011758:Pyrroles / Q000627:therapeutic use; D012186:Retroperitoneal Neoplasms / Q000188:drug therapy / Q000401:mortality; D012189:Retrospective Studies; D000077210:Sunitinib; D013498:Suramin / Q000627:therapeutic use; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000401:mortality; D019772:Topotecan / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D013498:Suramin; D019772:Topotecan; D000077210:Sunitinib