Phase 2 Trial of Capecitabine, Gemcitabine, and Bevacizumab in Sarcomatoid Renal-Cell Carcinoma

Abhishek Maiti, Maryam Nemati-Shafaee, Pavlos Msaouel, Lance C. Pagliaro, Eric Jonasch, Nizar M. Tannir, Amishi Y. Shah

Research output: Contribution to journalArticle

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Abstract

Background: Patients with sarcomatoid renal-cell carcinomas (sRCC) have poor outcomes and limited treatment options. Preclinical and clinical data suggest susceptibility to cytotoxic agents and vascular endothelial growth factor-targeted therapies. We designed a phase 2 trial to evaluate the efficacy and safety of capecitabine, gemcitabine, and bevacizumab in sRCC. Patients and Methods: Patients with metastatic or unresectable sRCC were eligible for inclusion. Patients received oral capecitabine 800 mg/m2 twice daily on days 1 to 21 of a 28-day cycle, intravenous gemcitabine 900 mg/m2 on days 1 and 15, and intravenous bevacizumab 10 mg/kg on days 1 and 15. Primary end points were progression-free survival and time to treatment failure (TTF). Secondary end points were safety, objective response rate, and overall survival. Results: Thirty-four patients were enrolled onto the trial. One patient was excluded from survival analysis and 4 from response analysis as a result of missing data. Median progression-free survival was 5.5 months (95% confidence interval [CI], 3.4-7.7), median TTF was 4.2 months (95% CI, 2.4-6.0), and median overall survival was 12 months (95% CI, 10.6-13.4). Objective response rate was 20% (5 partial responses, 1 complete response), and disease control rate was 73%. Thirty-one (91%) of the 34 patients discontinued treatment. The most common reason for treatment discontinuation was progressive disease, which occurred in 24 patients (71%). The most common grade 3 toxicity was rash (including hand-foot syndrome) in 24% patients. Conclusion: The combination of capecitabine, gemcitabine, and bevacizumab is an option for patients with sRCC; however, response rates are low. Novel therapies are needed to improve outcomes in patients with sRCC.

Original languageEnglish (US)
JournalClinical Genitourinary Cancer
DOIs
StateAccepted/In press - 2017

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gemcitabine
Renal Cell Carcinoma
Confidence Intervals
Treatment Failure
Disease-Free Survival
Bevacizumab
Capecitabine
Hand-Foot Syndrome
Safety

Keywords

  • Cytoxic chemotherapy
  • Metastatic renal-cell carcinoma
  • Renal-cell carcinoma (RCC)
  • Sarcomatoid
  • Sarcomatoid RCC

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Maiti, A., Nemati-Shafaee, M., Msaouel, P., Pagliaro, L. C., Jonasch, E., Tannir, N. M., & Shah, A. Y. (Accepted/In press). Phase 2 Trial of Capecitabine, Gemcitabine, and Bevacizumab in Sarcomatoid Renal-Cell Carcinoma. Clinical Genitourinary Cancer. https://doi.org/10.1016/j.clgc.2017.07.028

Phase 2 Trial of Capecitabine, Gemcitabine, and Bevacizumab in Sarcomatoid Renal-Cell Carcinoma. / Maiti, Abhishek; Nemati-Shafaee, Maryam; Msaouel, Pavlos; Pagliaro, Lance C.; Jonasch, Eric; Tannir, Nizar M.; Shah, Amishi Y.

In: Clinical Genitourinary Cancer, 2017.

Research output: Contribution to journalArticle

Maiti, Abhishek ; Nemati-Shafaee, Maryam ; Msaouel, Pavlos ; Pagliaro, Lance C. ; Jonasch, Eric ; Tannir, Nizar M. ; Shah, Amishi Y. / Phase 2 Trial of Capecitabine, Gemcitabine, and Bevacizumab in Sarcomatoid Renal-Cell Carcinoma. In: Clinical Genitourinary Cancer. 2017.
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abstract = "Background: Patients with sarcomatoid renal-cell carcinomas (sRCC) have poor outcomes and limited treatment options. Preclinical and clinical data suggest susceptibility to cytotoxic agents and vascular endothelial growth factor-targeted therapies. We designed a phase 2 trial to evaluate the efficacy and safety of capecitabine, gemcitabine, and bevacizumab in sRCC. Patients and Methods: Patients with metastatic or unresectable sRCC were eligible for inclusion. Patients received oral capecitabine 800 mg/m2 twice daily on days 1 to 21 of a 28-day cycle, intravenous gemcitabine 900 mg/m2 on days 1 and 15, and intravenous bevacizumab 10 mg/kg on days 1 and 15. Primary end points were progression-free survival and time to treatment failure (TTF). Secondary end points were safety, objective response rate, and overall survival. Results: Thirty-four patients were enrolled onto the trial. One patient was excluded from survival analysis and 4 from response analysis as a result of missing data. Median progression-free survival was 5.5 months (95{\%} confidence interval [CI], 3.4-7.7), median TTF was 4.2 months (95{\%} CI, 2.4-6.0), and median overall survival was 12 months (95{\%} CI, 10.6-13.4). Objective response rate was 20{\%} (5 partial responses, 1 complete response), and disease control rate was 73{\%}. Thirty-one (91{\%}) of the 34 patients discontinued treatment. The most common reason for treatment discontinuation was progressive disease, which occurred in 24 patients (71{\%}). The most common grade 3 toxicity was rash (including hand-foot syndrome) in 24{\%} patients. Conclusion: The combination of capecitabine, gemcitabine, and bevacizumab is an option for patients with sRCC; however, response rates are low. Novel therapies are needed to improve outcomes in patients with sRCC.",
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T1 - Phase 2 Trial of Capecitabine, Gemcitabine, and Bevacizumab in Sarcomatoid Renal-Cell Carcinoma

AU - Maiti, Abhishek

AU - Nemati-Shafaee, Maryam

AU - Msaouel, Pavlos

AU - Pagliaro, Lance C.

AU - Jonasch, Eric

AU - Tannir, Nizar M.

AU - Shah, Amishi Y.

PY - 2017

Y1 - 2017

N2 - Background: Patients with sarcomatoid renal-cell carcinomas (sRCC) have poor outcomes and limited treatment options. Preclinical and clinical data suggest susceptibility to cytotoxic agents and vascular endothelial growth factor-targeted therapies. We designed a phase 2 trial to evaluate the efficacy and safety of capecitabine, gemcitabine, and bevacizumab in sRCC. Patients and Methods: Patients with metastatic or unresectable sRCC were eligible for inclusion. Patients received oral capecitabine 800 mg/m2 twice daily on days 1 to 21 of a 28-day cycle, intravenous gemcitabine 900 mg/m2 on days 1 and 15, and intravenous bevacizumab 10 mg/kg on days 1 and 15. Primary end points were progression-free survival and time to treatment failure (TTF). Secondary end points were safety, objective response rate, and overall survival. Results: Thirty-four patients were enrolled onto the trial. One patient was excluded from survival analysis and 4 from response analysis as a result of missing data. Median progression-free survival was 5.5 months (95% confidence interval [CI], 3.4-7.7), median TTF was 4.2 months (95% CI, 2.4-6.0), and median overall survival was 12 months (95% CI, 10.6-13.4). Objective response rate was 20% (5 partial responses, 1 complete response), and disease control rate was 73%. Thirty-one (91%) of the 34 patients discontinued treatment. The most common reason for treatment discontinuation was progressive disease, which occurred in 24 patients (71%). The most common grade 3 toxicity was rash (including hand-foot syndrome) in 24% patients. Conclusion: The combination of capecitabine, gemcitabine, and bevacizumab is an option for patients with sRCC; however, response rates are low. Novel therapies are needed to improve outcomes in patients with sRCC.

AB - Background: Patients with sarcomatoid renal-cell carcinomas (sRCC) have poor outcomes and limited treatment options. Preclinical and clinical data suggest susceptibility to cytotoxic agents and vascular endothelial growth factor-targeted therapies. We designed a phase 2 trial to evaluate the efficacy and safety of capecitabine, gemcitabine, and bevacizumab in sRCC. Patients and Methods: Patients with metastatic or unresectable sRCC were eligible for inclusion. Patients received oral capecitabine 800 mg/m2 twice daily on days 1 to 21 of a 28-day cycle, intravenous gemcitabine 900 mg/m2 on days 1 and 15, and intravenous bevacizumab 10 mg/kg on days 1 and 15. Primary end points were progression-free survival and time to treatment failure (TTF). Secondary end points were safety, objective response rate, and overall survival. Results: Thirty-four patients were enrolled onto the trial. One patient was excluded from survival analysis and 4 from response analysis as a result of missing data. Median progression-free survival was 5.5 months (95% confidence interval [CI], 3.4-7.7), median TTF was 4.2 months (95% CI, 2.4-6.0), and median overall survival was 12 months (95% CI, 10.6-13.4). Objective response rate was 20% (5 partial responses, 1 complete response), and disease control rate was 73%. Thirty-one (91%) of the 34 patients discontinued treatment. The most common reason for treatment discontinuation was progressive disease, which occurred in 24 patients (71%). The most common grade 3 toxicity was rash (including hand-foot syndrome) in 24% patients. Conclusion: The combination of capecitabine, gemcitabine, and bevacizumab is an option for patients with sRCC; however, response rates are low. Novel therapies are needed to improve outcomes in patients with sRCC.

KW - Cytoxic chemotherapy

KW - Metastatic renal-cell carcinoma

KW - Renal-cell carcinoma (RCC)

KW - Sarcomatoid

KW - Sarcomatoid RCC

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