Progression-free and overall survival in patients with relapsed/refractory germ cell tumors treated with single-agent chemotherapy: Endpoints for clinical trial design Journal Article


Authors: Feldman, D. R.; Patil, S.; Trinos, M. J.; Carousso, M.; Ginsberg, M. S.; Sheinfeld, J.; Bajorin, D. F.; Bosl, G. J.; Motzer, R. J.
Article 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. © 2011 American Cancer Society.
Keywords: adolescent; adult; treatment outcome; major clinical study; overall survival; sunitinib; drug efficacy; temozolomide; topotecan; tumor localization; progression free survival; phase 2 clinical trial; cancer mortality; drug response; cancer relapse; germ cell tumor; germ cell tumors; retinoic acid; suramin; ixabepilone; phase ii trial; progression-free survival; clinical trial design; 2 (2 dimethylaminoethyl) 9 methoxy 5 nitropyrazolo[3,4,5 kl]acridine; relapsed or refractory
Journal Title: Cancer
Volume: 118
Issue: 4
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2012-02-15
Start Page: 981
End Page: 986
Language: English
DOI: 10.1002/cncr.26375
PROVIDER: scopus
PUBMED: 21792865
DOI/URL:
Notes: --- - "Export Date: 1 March 2012" - "CODEN: CANCA" - "Source: Scopus"
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MSK Authors
  1. Sujata Patil
    508 Patil
  2. Dean Bajorin
    637 Bajorin
  3. Robert Motzer
    1172 Motzer
  4. Michelle S Ginsberg
    223 Ginsberg
  5. Darren Richard Feldman
    310 Feldman
  6. Joel Sheinfeld
    245 Sheinfeld
  7. George Bosl
    428 Bosl
  8. Michael Joseph Trinos
    7 Trinos