TY - JOUR
T1 - Gemcitabine, cisplatin, and sunitinib for metastatic urothelial carcinoma and as preoperative therapy for muscle-invasive bladder cancer
AU - Galsky, Matthew D.
AU - Hahn, Noah M.
AU - Powles, Thomas
AU - Hellerstedt, Beth A.
AU - Lerner, Seth P.
AU - Gardner, Thomas A.
AU - Yu, Menggang
AU - O'Rourke, Mark
AU - Vogelzang, Nicholas J.
AU - Kocs, Darren
AU - McKenney, Scott A.
AU - Melnyk, Anton M.
AU - Hutson, Thomas E.
AU - Rauch, Mary
AU - Wang, Yunfei
AU - Asmar, Lina
AU - Sonpavde, Guru
N1 - Funding Information:
Trial 1 was supported by Pfizer Inc, US Medical Oncology, New York, NY, and trial 2 was supported by Pfizer Inc.
PY - 2013/6
Y1 - 2013/6
N2 - Background: Data support chemotherapy combined with antiangiogenic therapy in metastatic urothelial cancer (mUC) and muscle-invasive bladder cancer (MIBC). We investigated the efficacy and safety of gemcitabine, cisplatin, and sunitinib (GCS) in mUC and MIBC in parallel phase II trials. Patients and Methods: Trial 1 enrolled 36 patients with mUC who were chemotherapy naive; trial 2 enrolled 9 patients with MIBC. The primary endpoints for trials 1 and 2 were response rate and pathologic complete response, respectively. GCS was given as first-line treatment for patients with mUC and as neoadjuvant therapy for patients with MIBC. The Simon minimax 2-stage design was used for an objective response rate in trial 1 and for the pathologic complete response rate in trial 2. Results: The initial trial 1 GCS dose was gemcitabine 1000 mg/m2 intravenously, days 1 and 8; cisplatin 70 mg/m2 intravenously, day 1; and sunitinib 37.5 mg orally daily, days 1 to 14 of a 21-day cycle. These doses proved intolerable. The doses of gemcitabine and cisplatin were subsequently reduced to 800 and 60 mg/m2, respectively, without an improvement in drug delivery, and the trial was closed. This lower-dose regimen was applied in trial 2, which was stopped early due to excess toxicity. Grade 3 to 4 hematologic toxicities occurred in 70% (23/33) of patients in trial 1 and 22% (2/9) of patients in trial 2. In trial 1, the response rate was 49% (95% CI, 31%-67%); in trial 2, the pathologic complete response was 22% (2/9). Due to early closure secondary to toxicity, the sample sizes of both trials were small. Conclusions: Delivery of GCS was hampered by excessive toxicity in both advanced and neoadjuvant settings.
AB - Background: Data support chemotherapy combined with antiangiogenic therapy in metastatic urothelial cancer (mUC) and muscle-invasive bladder cancer (MIBC). We investigated the efficacy and safety of gemcitabine, cisplatin, and sunitinib (GCS) in mUC and MIBC in parallel phase II trials. Patients and Methods: Trial 1 enrolled 36 patients with mUC who were chemotherapy naive; trial 2 enrolled 9 patients with MIBC. The primary endpoints for trials 1 and 2 were response rate and pathologic complete response, respectively. GCS was given as first-line treatment for patients with mUC and as neoadjuvant therapy for patients with MIBC. The Simon minimax 2-stage design was used for an objective response rate in trial 1 and for the pathologic complete response rate in trial 2. Results: The initial trial 1 GCS dose was gemcitabine 1000 mg/m2 intravenously, days 1 and 8; cisplatin 70 mg/m2 intravenously, day 1; and sunitinib 37.5 mg orally daily, days 1 to 14 of a 21-day cycle. These doses proved intolerable. The doses of gemcitabine and cisplatin were subsequently reduced to 800 and 60 mg/m2, respectively, without an improvement in drug delivery, and the trial was closed. This lower-dose regimen was applied in trial 2, which was stopped early due to excess toxicity. Grade 3 to 4 hematologic toxicities occurred in 70% (23/33) of patients in trial 1 and 22% (2/9) of patients in trial 2. In trial 1, the response rate was 49% (95% CI, 31%-67%); in trial 2, the pathologic complete response was 22% (2/9). Due to early closure secondary to toxicity, the sample sizes of both trials were small. Conclusions: Delivery of GCS was hampered by excessive toxicity in both advanced and neoadjuvant settings.
KW - Antiangiogenic therapy
KW - Chemotherapy
KW - Hematologic toxicity
KW - Neoadjuvant
KW - Phase II
UR - http://www.scopus.com/inward/record.url?scp=84876982362&partnerID=8YFLogxK
U2 - 10.1016/j.clgc.2012.10.001
DO - 10.1016/j.clgc.2012.10.001
M3 - Article
C2 - 23228446
AN - SCOPUS:84876982362
SN - 1558-7673
VL - 11
SP - 175
EP - 181
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 2
ER -