SWOG S0809: A phase II intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extrahepatic cholangiocarcinoma and gallbladder carcinoma

Edgar Ben-Josef, Katherine A. Guthrie, Anthony B. El-Khoueiry, Christopher L. Corless, Mark M. Zalupski, Andrew M. Lowy, Charles R. Thomas, Steven Robert Alberts, Laura A. Dawson, Kenneth C. Micetich, Melanie B. Thomas, Abby B. Siegel, Charles D. Blanke

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Abstract

Purpose: The role of postoperative therapy in extrahepatic cholangiocarcinoma (EHCC) or gallbladder carcinoma (GBCA) is unknown. S0809 was designed to estimate 2-year survival (overall and after R0 or R1 resection), pattern of relapse, and toxicity in patients treated with this adjuvant regimen. Patients and Methods: Eligibility criteria included diagnosis of EHCC or GBCA after radical resection, stage pT2-4 or N+ or positive resection margins, M0, and performance status 0 to 1. Patients received four cycles of gemcitabine (1,000 mg/m<sup>2</sup> intravenously on days 1 and 8) and capecitabine (1,500 mg/m<sup>2</sup> per day on days 1 to 14) every 21 days followed by concurrent capecitabine (1,330 mg/m<sup>2</sup> per day) and radiotherapy (45 Gy to regional lymphatics; 54 to 59.4 Gy to tumor bed). With 80 evaluable patients, results would be promising if 2-year survival 95% CI were > 45% and R0 and R1 survival estimates were ≥ 65% and 45%, respectively. Results: A total of 79 eligible patients (R0, n = 54; R1, n = 25; EHCC, 68%; GBCA, 32%) were treated (86% completed). For all patients, 2-year survival was 65% (95% CI, 53% to 74%); it was 67% and 60% in R0 and R1 patients, respectively. Median overall survival was 35 months (R0, 34 months; R1, 35 months). Local, distant, and combined relapse occurred in 14, 24, and nine patients. Grade 3 and 4 adverse effects were observed in 52% and 11% of patients, respectively. The most common grade 3 to 4 adverse effects were neutropenia (44%), hand-foot syndrome (11%), diarrhea (8%), lymphopenia (8%), and leukopenia (6%). There was one death resulting from GI hemorrhage. Conclusion: This combination was well tolerated, has promising efficacy, and provides clinicians with a well-supported regimen. Our trial establishes the feasibility of conducting national adjuvant trials in EHCC and GBCA and provides baseline data for planning future phase III trials.

Original languageEnglish (US)
Pages (from-to)2617-2622
Number of pages6
JournalJournal of Clinical Oncology
Volume33
Issue number24
DOIs
StatePublished - Aug 20 2015

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gemcitabine
Cholangiocarcinoma
Gallbladder
Radiotherapy
Carcinoma
Survival
Hand-Foot Syndrome
Capecitabine
Recurrence
Lymphopenia
Leukopenia
Neutropenia

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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SWOG S0809 : A phase II intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extrahepatic cholangiocarcinoma and gallbladder carcinoma. / Ben-Josef, Edgar; Guthrie, Katherine A.; El-Khoueiry, Anthony B.; Corless, Christopher L.; Zalupski, Mark M.; Lowy, Andrew M.; Thomas, Charles R.; Alberts, Steven Robert; Dawson, Laura A.; Micetich, Kenneth C.; Thomas, Melanie B.; Siegel, Abby B.; Blanke, Charles D.

In: Journal of Clinical Oncology, Vol. 33, No. 24, 20.08.2015, p. 2617-2622.

Research output: Contribution to journalArticle

Ben-Josef, E, Guthrie, KA, El-Khoueiry, AB, Corless, CL, Zalupski, MM, Lowy, AM, Thomas, CR, Alberts, SR, Dawson, LA, Micetich, KC, Thomas, MB, Siegel, AB & Blanke, CD 2015, 'SWOG S0809: A phase II intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extrahepatic cholangiocarcinoma and gallbladder carcinoma', Journal of Clinical Oncology, vol. 33, no. 24, pp. 2617-2622. https://doi.org/10.1200/JCO.2014.60.2219
Ben-Josef, Edgar ; Guthrie, Katherine A. ; El-Khoueiry, Anthony B. ; Corless, Christopher L. ; Zalupski, Mark M. ; Lowy, Andrew M. ; Thomas, Charles R. ; Alberts, Steven Robert ; Dawson, Laura A. ; Micetich, Kenneth C. ; Thomas, Melanie B. ; Siegel, Abby B. ; Blanke, Charles D. / SWOG S0809 : A phase II intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extrahepatic cholangiocarcinoma and gallbladder carcinoma. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 24. pp. 2617-2622.
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abstract = "Purpose: The role of postoperative therapy in extrahepatic cholangiocarcinoma (EHCC) or gallbladder carcinoma (GBCA) is unknown. S0809 was designed to estimate 2-year survival (overall and after R0 or R1 resection), pattern of relapse, and toxicity in patients treated with this adjuvant regimen. Patients and Methods: Eligibility criteria included diagnosis of EHCC or GBCA after radical resection, stage pT2-4 or N+ or positive resection margins, M0, and performance status 0 to 1. Patients received four cycles of gemcitabine (1,000 mg/m2 intravenously on days 1 and 8) and capecitabine (1,500 mg/m2 per day on days 1 to 14) every 21 days followed by concurrent capecitabine (1,330 mg/m2 per day) and radiotherapy (45 Gy to regional lymphatics; 54 to 59.4 Gy to tumor bed). With 80 evaluable patients, results would be promising if 2-year survival 95{\%} CI were > 45{\%} and R0 and R1 survival estimates were ≥ 65{\%} and 45{\%}, respectively. Results: A total of 79 eligible patients (R0, n = 54; R1, n = 25; EHCC, 68{\%}; GBCA, 32{\%}) were treated (86{\%} completed). For all patients, 2-year survival was 65{\%} (95{\%} CI, 53{\%} to 74{\%}); it was 67{\%} and 60{\%} in R0 and R1 patients, respectively. Median overall survival was 35 months (R0, 34 months; R1, 35 months). Local, distant, and combined relapse occurred in 14, 24, and nine patients. Grade 3 and 4 adverse effects were observed in 52{\%} and 11{\%} of patients, respectively. The most common grade 3 to 4 adverse effects were neutropenia (44{\%}), hand-foot syndrome (11{\%}), diarrhea (8{\%}), lymphopenia (8{\%}), and leukopenia (6{\%}). There was one death resulting from GI hemorrhage. Conclusion: This combination was well tolerated, has promising efficacy, and provides clinicians with a well-supported regimen. Our trial establishes the feasibility of conducting national adjuvant trials in EHCC and GBCA and provides baseline data for planning future phase III trials.",
author = "Edgar Ben-Josef and Guthrie, {Katherine A.} and El-Khoueiry, {Anthony B.} and Corless, {Christopher L.} and Zalupski, {Mark M.} and Lowy, {Andrew M.} and Thomas, {Charles R.} and Alberts, {Steven Robert} and Dawson, {Laura A.} and Micetich, {Kenneth C.} and Thomas, {Melanie B.} and Siegel, {Abby B.} and Blanke, {Charles D.}",
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T2 - A phase II intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extrahepatic cholangiocarcinoma and gallbladder carcinoma

AU - Ben-Josef, Edgar

AU - Guthrie, Katherine A.

AU - El-Khoueiry, Anthony B.

AU - Corless, Christopher L.

AU - Zalupski, Mark M.

AU - Lowy, Andrew M.

AU - Thomas, Charles R.

AU - Alberts, Steven Robert

AU - Dawson, Laura A.

AU - Micetich, Kenneth C.

AU - Thomas, Melanie B.

AU - Siegel, Abby B.

AU - Blanke, Charles D.

PY - 2015/8/20

Y1 - 2015/8/20

N2 - Purpose: The role of postoperative therapy in extrahepatic cholangiocarcinoma (EHCC) or gallbladder carcinoma (GBCA) is unknown. S0809 was designed to estimate 2-year survival (overall and after R0 or R1 resection), pattern of relapse, and toxicity in patients treated with this adjuvant regimen. Patients and Methods: Eligibility criteria included diagnosis of EHCC or GBCA after radical resection, stage pT2-4 or N+ or positive resection margins, M0, and performance status 0 to 1. Patients received four cycles of gemcitabine (1,000 mg/m2 intravenously on days 1 and 8) and capecitabine (1,500 mg/m2 per day on days 1 to 14) every 21 days followed by concurrent capecitabine (1,330 mg/m2 per day) and radiotherapy (45 Gy to regional lymphatics; 54 to 59.4 Gy to tumor bed). With 80 evaluable patients, results would be promising if 2-year survival 95% CI were > 45% and R0 and R1 survival estimates were ≥ 65% and 45%, respectively. Results: A total of 79 eligible patients (R0, n = 54; R1, n = 25; EHCC, 68%; GBCA, 32%) were treated (86% completed). For all patients, 2-year survival was 65% (95% CI, 53% to 74%); it was 67% and 60% in R0 and R1 patients, respectively. Median overall survival was 35 months (R0, 34 months; R1, 35 months). Local, distant, and combined relapse occurred in 14, 24, and nine patients. Grade 3 and 4 adverse effects were observed in 52% and 11% of patients, respectively. The most common grade 3 to 4 adverse effects were neutropenia (44%), hand-foot syndrome (11%), diarrhea (8%), lymphopenia (8%), and leukopenia (6%). There was one death resulting from GI hemorrhage. Conclusion: This combination was well tolerated, has promising efficacy, and provides clinicians with a well-supported regimen. Our trial establishes the feasibility of conducting national adjuvant trials in EHCC and GBCA and provides baseline data for planning future phase III trials.

AB - Purpose: The role of postoperative therapy in extrahepatic cholangiocarcinoma (EHCC) or gallbladder carcinoma (GBCA) is unknown. S0809 was designed to estimate 2-year survival (overall and after R0 or R1 resection), pattern of relapse, and toxicity in patients treated with this adjuvant regimen. Patients and Methods: Eligibility criteria included diagnosis of EHCC or GBCA after radical resection, stage pT2-4 or N+ or positive resection margins, M0, and performance status 0 to 1. Patients received four cycles of gemcitabine (1,000 mg/m2 intravenously on days 1 and 8) and capecitabine (1,500 mg/m2 per day on days 1 to 14) every 21 days followed by concurrent capecitabine (1,330 mg/m2 per day) and radiotherapy (45 Gy to regional lymphatics; 54 to 59.4 Gy to tumor bed). With 80 evaluable patients, results would be promising if 2-year survival 95% CI were > 45% and R0 and R1 survival estimates were ≥ 65% and 45%, respectively. Results: A total of 79 eligible patients (R0, n = 54; R1, n = 25; EHCC, 68%; GBCA, 32%) were treated (86% completed). For all patients, 2-year survival was 65% (95% CI, 53% to 74%); it was 67% and 60% in R0 and R1 patients, respectively. Median overall survival was 35 months (R0, 34 months; R1, 35 months). Local, distant, and combined relapse occurred in 14, 24, and nine patients. Grade 3 and 4 adverse effects were observed in 52% and 11% of patients, respectively. The most common grade 3 to 4 adverse effects were neutropenia (44%), hand-foot syndrome (11%), diarrhea (8%), lymphopenia (8%), and leukopenia (6%). There was one death resulting from GI hemorrhage. Conclusion: This combination was well tolerated, has promising efficacy, and provides clinicians with a well-supported regimen. Our trial establishes the feasibility of conducting national adjuvant trials in EHCC and GBCA and provides baseline data for planning future phase III trials.

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