Phase II trial of full-dose gemcitabine and bevacizumab in combination with attenuated three-dimensional conformal radiotherapy in patients with localized pancreatic cancer

William Small*, Mary Frances Mulcahy, Alfred W Rademaker, David Jason Bentrem, Al B Benson III, Bing Bing Weitner, Mark S. Talamonti

*Corresponding author for this work

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Purpose: To evaluate response rate, survival, and toxicity in patients with nonmetastatic pancreatic cancer treated with gemcitabine, bevacizumab, and radiotherapy. Methods and Materials: Patients received three cycles of therapy over 10 weeks. In total, treatment consisted of intravenous (IV) gemcitabine, 1,000 mg/m2, every 1 to 2 weeks (7 doses), IV bevacizumab, 10 mg/kg every 2 weeks (5 doses), and 36 Gy of radiotherapy (2.4-Gy fractions during cycle two). Response was assessed by cross-sectional imaging and carbohydrate antigen 19-9 (CA 19-9) levels. Patients with resectable tumors underwent surgery 6 to 8 weeks after the last dose of bevacizumab. Maintenance gemcitabine and bevacizumab doses were delivered to patients who had unresected tumors and no progression. Results: Twenty-eight of the 32 enrolled patients completed all three cycles. The median follow-up was 11.07 months. Most grade 3 or 4 toxicities occurred in the initial treatment phase; the most frequent toxicities were leukopenia (21%), neutropenia (17%), and nausea (17%). At week 10, 1 patient (4%) had a complete response, 2 patients (7%) had partial responses, 21 patients (75%) had stable disease, and 4 patients (14%) had progressive disease. The median pretreatment and posttreatment CA 19-9 levels (25 patients) were 184.3 and 57.9 U/ml, respectively (p = 0.0006). One of 10 patients proceeding to surgery experienced a major complication. Two of 6 patients undergoing resection had complete pathologic responses. The median progression-free and overall survival durations were 9.9 months and 11.8 months, respectively. Conclusions: The combination of full-dose gemcitabine, bevacizumab, and radiotherapy was active and was not associated with a high rate of major surgical complications.

Original languageEnglish (US)
Pages (from-to)476-482
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume80
Issue number2
DOIs
StatePublished - Jun 1 2011

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gemcitabine
Conformal Radiotherapy
Pancreatic Neoplasms
radiation therapy
cancer
dosage
toxicity
Radiotherapy
carbohydrates
antigens
surgery
progressions
cycles
Bevacizumab
tumors
leukopenia
Carbohydrates
nausea
Antigens

Keywords

  • 3D conformal radiotherapy
  • Bevacizumab
  • Gemcitabine
  • Pancreatic cancer
  • Survival

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

@article{f9b77c2b231d4d97957b9aa2be199bf5,
title = "Phase II trial of full-dose gemcitabine and bevacizumab in combination with attenuated three-dimensional conformal radiotherapy in patients with localized pancreatic cancer",
abstract = "Purpose: To evaluate response rate, survival, and toxicity in patients with nonmetastatic pancreatic cancer treated with gemcitabine, bevacizumab, and radiotherapy. Methods and Materials: Patients received three cycles of therapy over 10 weeks. In total, treatment consisted of intravenous (IV) gemcitabine, 1,000 mg/m2, every 1 to 2 weeks (7 doses), IV bevacizumab, 10 mg/kg every 2 weeks (5 doses), and 36 Gy of radiotherapy (2.4-Gy fractions during cycle two). Response was assessed by cross-sectional imaging and carbohydrate antigen 19-9 (CA 19-9) levels. Patients with resectable tumors underwent surgery 6 to 8 weeks after the last dose of bevacizumab. Maintenance gemcitabine and bevacizumab doses were delivered to patients who had unresected tumors and no progression. Results: Twenty-eight of the 32 enrolled patients completed all three cycles. The median follow-up was 11.07 months. Most grade 3 or 4 toxicities occurred in the initial treatment phase; the most frequent toxicities were leukopenia (21{\%}), neutropenia (17{\%}), and nausea (17{\%}). At week 10, 1 patient (4{\%}) had a complete response, 2 patients (7{\%}) had partial responses, 21 patients (75{\%}) had stable disease, and 4 patients (14{\%}) had progressive disease. The median pretreatment and posttreatment CA 19-9 levels (25 patients) were 184.3 and 57.9 U/ml, respectively (p = 0.0006). One of 10 patients proceeding to surgery experienced a major complication. Two of 6 patients undergoing resection had complete pathologic responses. The median progression-free and overall survival durations were 9.9 months and 11.8 months, respectively. Conclusions: The combination of full-dose gemcitabine, bevacizumab, and radiotherapy was active and was not associated with a high rate of major surgical complications.",
keywords = "3D conformal radiotherapy, Bevacizumab, Gemcitabine, Pancreatic cancer, Survival",
author = "William Small and Mulcahy, {Mary Frances} and Rademaker, {Alfred W} and Bentrem, {David Jason} and {Benson III}, {Al B} and Weitner, {Bing Bing} and Talamonti, {Mark S.}",
year = "2011",
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language = "English (US)",
volume = "80",
pages = "476--482",
journal = "International Journal of Radiation Oncology Biology Physics",
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TY - JOUR

T1 - Phase II trial of full-dose gemcitabine and bevacizumab in combination with attenuated three-dimensional conformal radiotherapy in patients with localized pancreatic cancer

AU - Small, William

AU - Mulcahy, Mary Frances

AU - Rademaker, Alfred W

AU - Bentrem, David Jason

AU - Benson III, Al B

AU - Weitner, Bing Bing

AU - Talamonti, Mark S.

PY - 2011/6/1

Y1 - 2011/6/1

N2 - Purpose: To evaluate response rate, survival, and toxicity in patients with nonmetastatic pancreatic cancer treated with gemcitabine, bevacizumab, and radiotherapy. Methods and Materials: Patients received three cycles of therapy over 10 weeks. In total, treatment consisted of intravenous (IV) gemcitabine, 1,000 mg/m2, every 1 to 2 weeks (7 doses), IV bevacizumab, 10 mg/kg every 2 weeks (5 doses), and 36 Gy of radiotherapy (2.4-Gy fractions during cycle two). Response was assessed by cross-sectional imaging and carbohydrate antigen 19-9 (CA 19-9) levels. Patients with resectable tumors underwent surgery 6 to 8 weeks after the last dose of bevacizumab. Maintenance gemcitabine and bevacizumab doses were delivered to patients who had unresected tumors and no progression. Results: Twenty-eight of the 32 enrolled patients completed all three cycles. The median follow-up was 11.07 months. Most grade 3 or 4 toxicities occurred in the initial treatment phase; the most frequent toxicities were leukopenia (21%), neutropenia (17%), and nausea (17%). At week 10, 1 patient (4%) had a complete response, 2 patients (7%) had partial responses, 21 patients (75%) had stable disease, and 4 patients (14%) had progressive disease. The median pretreatment and posttreatment CA 19-9 levels (25 patients) were 184.3 and 57.9 U/ml, respectively (p = 0.0006). One of 10 patients proceeding to surgery experienced a major complication. Two of 6 patients undergoing resection had complete pathologic responses. The median progression-free and overall survival durations were 9.9 months and 11.8 months, respectively. Conclusions: The combination of full-dose gemcitabine, bevacizumab, and radiotherapy was active and was not associated with a high rate of major surgical complications.

AB - Purpose: To evaluate response rate, survival, and toxicity in patients with nonmetastatic pancreatic cancer treated with gemcitabine, bevacizumab, and radiotherapy. Methods and Materials: Patients received three cycles of therapy over 10 weeks. In total, treatment consisted of intravenous (IV) gemcitabine, 1,000 mg/m2, every 1 to 2 weeks (7 doses), IV bevacizumab, 10 mg/kg every 2 weeks (5 doses), and 36 Gy of radiotherapy (2.4-Gy fractions during cycle two). Response was assessed by cross-sectional imaging and carbohydrate antigen 19-9 (CA 19-9) levels. Patients with resectable tumors underwent surgery 6 to 8 weeks after the last dose of bevacizumab. Maintenance gemcitabine and bevacizumab doses were delivered to patients who had unresected tumors and no progression. Results: Twenty-eight of the 32 enrolled patients completed all three cycles. The median follow-up was 11.07 months. Most grade 3 or 4 toxicities occurred in the initial treatment phase; the most frequent toxicities were leukopenia (21%), neutropenia (17%), and nausea (17%). At week 10, 1 patient (4%) had a complete response, 2 patients (7%) had partial responses, 21 patients (75%) had stable disease, and 4 patients (14%) had progressive disease. The median pretreatment and posttreatment CA 19-9 levels (25 patients) were 184.3 and 57.9 U/ml, respectively (p = 0.0006). One of 10 patients proceeding to surgery experienced a major complication. Two of 6 patients undergoing resection had complete pathologic responses. The median progression-free and overall survival durations were 9.9 months and 11.8 months, respectively. Conclusions: The combination of full-dose gemcitabine, bevacizumab, and radiotherapy was active and was not associated with a high rate of major surgical complications.

KW - 3D conformal radiotherapy

KW - Bevacizumab

KW - Gemcitabine

KW - Pancreatic cancer

KW - Survival

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