Phase II trial of cisplatin, gemcitabine, and bevacizumab as first-line therapy for metastatic urothelial carcinoma: Hoosier oncology group GU 04-75

Noah M. Hahn, Walter M. Stadler, Robin T. Zon, David Waterhouse, Joel Picus, Sreenivasa Nattam, Cynthia S. Johnson, Susan Perkins, Mary Jane Waddell, Christopher J. Sweeney

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Abstract

Purpose Novel approaches are needed for patients with metastatic urothelial cancer (UC). This trial assessed the efficacy and toxicity of bevacizumab in combination with cisplatin and gemcitabine (CGB) as first-line treatment for patients with metastatic UC. Patients and Methods Chemotherapy-naive patients with metastatic or unresectable UC received cisplatin 70 mg/m2 on day 1, gemcitabine 1,000 to 1,250 mg/m2 on days 1 and 8, and bevacizumab 15 mg/kg on day 1, every 21 days. Results Forty-three patients with performance status of 0 (n=26) or 1 (n=17) and median age of 66 years were evaluable for toxicity and response. Grade 3 to 4 hematologic toxicity included neutropenia (35%), thrombocytopenia (12%), anemia (12%), and neutropenic fever (2%). Grade 3 to 5 nonhematologic toxicity included deep vein thrombosis/pulmonary embolism (21%), hemorrhage (7%), cardiac (7%), hypertension (5%), and proteinuria (2%). Three treatment-related deaths (CNS hemorrhage, sudden cardiac death, and aortic dissection) were observed. Best response by Response Evaluation Criteria in Solid Tumors was complete response in eight patients (19%) and partial response in 23 patients (53%), for an overall response rate of 72%. Stable disease lasting ≥ 12 weeks occurred in four patients (9%), and progressive disease occurred in six patients (14%). With a median follow-up of 27.2 months (range, 3.5 to 40.9 months), median progressionfree survival (PFS) was 8.2 months (95% CI, 6.8 to 10.3 months) with a median overall survival (OS) time of 19.1 months (95% CI, 12.4 to 22.7 months). The study-defined goal of 50% improvement in PFS was not met. Conclusion CGB demonstrates promising OS and antiangiogenic treatment-related toxicities in the phase II setting of metastatic UC. The full risk/benefit profile of CGB in patients with metastatic UC will be determined by an ongoing phase III intergroup trial.

Original languageEnglish
Pages (from-to)1525-1530
Number of pages6
JournalJournal of Clinical Oncology
Volume29
Issue number12
DOIs
StatePublished - Apr 20 2011

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gemcitabine
Cisplatin
Carcinoma
Therapeutics
Survival
Neoplasms
Bevacizumab
Hemorrhage
Sudden Cardiac Death

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Phase II trial of cisplatin, gemcitabine, and bevacizumab as first-line therapy for metastatic urothelial carcinoma : Hoosier oncology group GU 04-75. / Hahn, Noah M.; Stadler, Walter M.; Zon, Robin T.; Waterhouse, David; Picus, Joel; Nattam, Sreenivasa; Johnson, Cynthia S.; Perkins, Susan; Waddell, Mary Jane; Sweeney, Christopher J.

In: Journal of Clinical Oncology, Vol. 29, No. 12, 20.04.2011, p. 1525-1530.

Research output: Contribution to journalArticle

Hahn, Noah M. ; Stadler, Walter M. ; Zon, Robin T. ; Waterhouse, David ; Picus, Joel ; Nattam, Sreenivasa ; Johnson, Cynthia S. ; Perkins, Susan ; Waddell, Mary Jane ; Sweeney, Christopher J. / Phase II trial of cisplatin, gemcitabine, and bevacizumab as first-line therapy for metastatic urothelial carcinoma : Hoosier oncology group GU 04-75. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 12. pp. 1525-1530.
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title = "Phase II trial of cisplatin, gemcitabine, and bevacizumab as first-line therapy for metastatic urothelial carcinoma: Hoosier oncology group GU 04-75",
abstract = "Purpose Novel approaches are needed for patients with metastatic urothelial cancer (UC). This trial assessed the efficacy and toxicity of bevacizumab in combination with cisplatin and gemcitabine (CGB) as first-line treatment for patients with metastatic UC. Patients and Methods Chemotherapy-naive patients with metastatic or unresectable UC received cisplatin 70 mg/m2 on day 1, gemcitabine 1,000 to 1,250 mg/m2 on days 1 and 8, and bevacizumab 15 mg/kg on day 1, every 21 days. Results Forty-three patients with performance status of 0 (n=26) or 1 (n=17) and median age of 66 years were evaluable for toxicity and response. Grade 3 to 4 hematologic toxicity included neutropenia (35{\%}), thrombocytopenia (12{\%}), anemia (12{\%}), and neutropenic fever (2{\%}). Grade 3 to 5 nonhematologic toxicity included deep vein thrombosis/pulmonary embolism (21{\%}), hemorrhage (7{\%}), cardiac (7{\%}), hypertension (5{\%}), and proteinuria (2{\%}). Three treatment-related deaths (CNS hemorrhage, sudden cardiac death, and aortic dissection) were observed. Best response by Response Evaluation Criteria in Solid Tumors was complete response in eight patients (19{\%}) and partial response in 23 patients (53{\%}), for an overall response rate of 72{\%}. Stable disease lasting ≥ 12 weeks occurred in four patients (9{\%}), and progressive disease occurred in six patients (14{\%}). With a median follow-up of 27.2 months (range, 3.5 to 40.9 months), median progressionfree survival (PFS) was 8.2 months (95{\%} CI, 6.8 to 10.3 months) with a median overall survival (OS) time of 19.1 months (95{\%} CI, 12.4 to 22.7 months). The study-defined goal of 50{\%} improvement in PFS was not met. Conclusion CGB demonstrates promising OS and antiangiogenic treatment-related toxicities in the phase II setting of metastatic UC. The full risk/benefit profile of CGB in patients with metastatic UC will be determined by an ongoing phase III intergroup trial.",
author = "Hahn, {Noah M.} and Stadler, {Walter M.} and Zon, {Robin T.} and David Waterhouse and Joel Picus and Sreenivasa Nattam and Johnson, {Cynthia S.} and Susan Perkins and Waddell, {Mary Jane} and Sweeney, {Christopher J.}",
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T1 - Phase II trial of cisplatin, gemcitabine, and bevacizumab as first-line therapy for metastatic urothelial carcinoma

T2 - Hoosier oncology group GU 04-75

AU - Hahn, Noah M.

AU - Stadler, Walter M.

AU - Zon, Robin T.

AU - Waterhouse, David

AU - Picus, Joel

AU - Nattam, Sreenivasa

AU - Johnson, Cynthia S.

AU - Perkins, Susan

AU - Waddell, Mary Jane

AU - Sweeney, Christopher J.

PY - 2011/4/20

Y1 - 2011/4/20

N2 - Purpose Novel approaches are needed for patients with metastatic urothelial cancer (UC). This trial assessed the efficacy and toxicity of bevacizumab in combination with cisplatin and gemcitabine (CGB) as first-line treatment for patients with metastatic UC. Patients and Methods Chemotherapy-naive patients with metastatic or unresectable UC received cisplatin 70 mg/m2 on day 1, gemcitabine 1,000 to 1,250 mg/m2 on days 1 and 8, and bevacizumab 15 mg/kg on day 1, every 21 days. Results Forty-three patients with performance status of 0 (n=26) or 1 (n=17) and median age of 66 years were evaluable for toxicity and response. Grade 3 to 4 hematologic toxicity included neutropenia (35%), thrombocytopenia (12%), anemia (12%), and neutropenic fever (2%). Grade 3 to 5 nonhematologic toxicity included deep vein thrombosis/pulmonary embolism (21%), hemorrhage (7%), cardiac (7%), hypertension (5%), and proteinuria (2%). Three treatment-related deaths (CNS hemorrhage, sudden cardiac death, and aortic dissection) were observed. Best response by Response Evaluation Criteria in Solid Tumors was complete response in eight patients (19%) and partial response in 23 patients (53%), for an overall response rate of 72%. Stable disease lasting ≥ 12 weeks occurred in four patients (9%), and progressive disease occurred in six patients (14%). With a median follow-up of 27.2 months (range, 3.5 to 40.9 months), median progressionfree survival (PFS) was 8.2 months (95% CI, 6.8 to 10.3 months) with a median overall survival (OS) time of 19.1 months (95% CI, 12.4 to 22.7 months). The study-defined goal of 50% improvement in PFS was not met. Conclusion CGB demonstrates promising OS and antiangiogenic treatment-related toxicities in the phase II setting of metastatic UC. The full risk/benefit profile of CGB in patients with metastatic UC will be determined by an ongoing phase III intergroup trial.

AB - Purpose Novel approaches are needed for patients with metastatic urothelial cancer (UC). This trial assessed the efficacy and toxicity of bevacizumab in combination with cisplatin and gemcitabine (CGB) as first-line treatment for patients with metastatic UC. Patients and Methods Chemotherapy-naive patients with metastatic or unresectable UC received cisplatin 70 mg/m2 on day 1, gemcitabine 1,000 to 1,250 mg/m2 on days 1 and 8, and bevacizumab 15 mg/kg on day 1, every 21 days. Results Forty-three patients with performance status of 0 (n=26) or 1 (n=17) and median age of 66 years were evaluable for toxicity and response. Grade 3 to 4 hematologic toxicity included neutropenia (35%), thrombocytopenia (12%), anemia (12%), and neutropenic fever (2%). Grade 3 to 5 nonhematologic toxicity included deep vein thrombosis/pulmonary embolism (21%), hemorrhage (7%), cardiac (7%), hypertension (5%), and proteinuria (2%). Three treatment-related deaths (CNS hemorrhage, sudden cardiac death, and aortic dissection) were observed. Best response by Response Evaluation Criteria in Solid Tumors was complete response in eight patients (19%) and partial response in 23 patients (53%), for an overall response rate of 72%. Stable disease lasting ≥ 12 weeks occurred in four patients (9%), and progressive disease occurred in six patients (14%). With a median follow-up of 27.2 months (range, 3.5 to 40.9 months), median progressionfree survival (PFS) was 8.2 months (95% CI, 6.8 to 10.3 months) with a median overall survival (OS) time of 19.1 months (95% CI, 12.4 to 22.7 months). The study-defined goal of 50% improvement in PFS was not met. Conclusion CGB demonstrates promising OS and antiangiogenic treatment-related toxicities in the phase II setting of metastatic UC. The full risk/benefit profile of CGB in patients with metastatic UC will be determined by an ongoing phase III intergroup trial.

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