Gemcitabine, cisplatin, and sunitinib for metastatic urothelial carcinoma and as preoperative therapy for muscle-invasive bladder cancer

Matthew D. Galsky, Noah M. Hahn, Thomas Powles, Beth A. Hellerstedt, Seth P. Lerner, Thomas Gardner, Menggang Yu, Mark O'Rourke, Nicholas J. Vogelzang, Darren Kocs, Scott A. McKenney, Anton M. Melnyk, Thomas E. Hutson, Mary Rauch, Yunfei Wang, Lina Asmar, Guru Sonpavde

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Abstract

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.

Original languageEnglish
Pages (from-to)175-181
Number of pages7
JournalClinical Genitourinary Cancer
Volume11
Issue number2
DOIs
StatePublished - Jun 2013

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gemcitabine
Urinary Bladder Neoplasms
Cisplatin
Carcinoma
Muscles
Muscle Neoplasms
Therapeutics
Drug Therapy
Neoadjuvant Therapy
sunitinib
Sample Size
Neoplasms

Keywords

  • Antiangiogenic therapy
  • Chemotherapy
  • Hematologic toxicity
  • Neoadjuvant
  • Phase II

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Gemcitabine, cisplatin, and sunitinib for metastatic urothelial carcinoma and as preoperative therapy for muscle-invasive bladder cancer. / Galsky, Matthew D.; Hahn, Noah M.; Powles, Thomas; Hellerstedt, Beth A.; Lerner, Seth P.; Gardner, Thomas; Yu, Menggang; O'Rourke, Mark; Vogelzang, Nicholas J.; Kocs, Darren; McKenney, Scott A.; Melnyk, Anton M.; Hutson, Thomas E.; Rauch, Mary; Wang, Yunfei; Asmar, Lina; Sonpavde, Guru.

In: Clinical Genitourinary Cancer, Vol. 11, No. 2, 06.2013, p. 175-181.

Research output: Contribution to journalArticle

Galsky, MD, Hahn, NM, Powles, T, Hellerstedt, BA, Lerner, SP, Gardner, T, Yu, M, O'Rourke, M, Vogelzang, NJ, Kocs, D, McKenney, SA, Melnyk, AM, Hutson, TE, Rauch, M, Wang, Y, Asmar, L & Sonpavde, G 2013, 'Gemcitabine, cisplatin, and sunitinib for metastatic urothelial carcinoma and as preoperative therapy for muscle-invasive bladder cancer', Clinical Genitourinary Cancer, vol. 11, no. 2, pp. 175-181. https://doi.org/10.1016/j.clgc.2012.10.001
Galsky, Matthew D. ; Hahn, Noah M. ; Powles, Thomas ; Hellerstedt, Beth A. ; Lerner, Seth P. ; Gardner, Thomas ; Yu, Menggang ; O'Rourke, Mark ; Vogelzang, Nicholas J. ; Kocs, Darren ; McKenney, Scott A. ; Melnyk, Anton M. ; Hutson, Thomas E. ; Rauch, Mary ; Wang, Yunfei ; Asmar, Lina ; Sonpavde, Guru. / Gemcitabine, cisplatin, and sunitinib for metastatic urothelial carcinoma and as preoperative therapy for muscle-invasive bladder cancer. In: Clinical Genitourinary Cancer. 2013 ; Vol. 11, No. 2. pp. 175-181.
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abstract = "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.",
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AU - Hahn, Noah M.

AU - Powles, Thomas

AU - Hellerstedt, Beth A.

AU - Lerner, Seth P.

AU - Gardner, Thomas

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

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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.

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