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Progression‐free and overall survival in patients with relapsed/refractory germ cell tumors treated with single‐agent chemotherapy: Endpoints for clinical trial design
Author(s) -
Feldman Darren R.,
Patil Sujata,
Trinos Michael J.,
Carousso Maryann,
Ginsberg Michelle S.,
Sheinfeld Joel,
Bajorin Dean F.,
Bosl George J.,
Motzer Robert J.
Publication year - 2011
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.26375
Subject(s) - medicine , clinical endpoint , ixabepilone , progression free survival , germ cell tumors , phases of clinical research , population , refractory (planetary science) , surgery , oncology , hazard ratio , chemotherapy regimen , response evaluation criteria in solid tumors , salvage therapy , progressive disease , clinical trial , cancer , chemotherapy , confidence interval , metastatic breast cancer , breast cancer , physics , environmental health , astrobiology
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. Cancer 2012;. © 2011 American Cancer Society.