TY - JOUR
T1 - Phase II Study of Weekly Intravenous Oxaliplatin Combined With Oral Daily Capecitabine and Radiotherapy With Biologic Correlates in Neoadjuvant Treatment of Rectal Adenocarcinoma
AU - Fakih, Marwan G.
AU - BullardDunn, Kelli
AU - Yang, Gary Y.
AU - Pendyala, Lakshmi
AU - Toth, Karoly
AU - Andrews, Chris
AU - Rustum, Youcef M.
AU - Ross, Mary Ellen
AU - LeVea, Charles
AU - Puthillath, Ajithkumar
AU - Park, Young Mee
AU - Rajput, Ashwani
N1 - Funding Information:
Supported by a grant from Sanofi Pharmaceuticals, Cancer Center Support Grant CA16056, and American Cancer Society Grant MRSG-04-270-01.
Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2008/11/1
Y1 - 2008/11/1
N2 - Purpose: To evaluate the efficacy of a combination of capecitabine, oxaliplatin, and radiotherapy (RT) in the neoadjuvant treatment of Stage II and III rectal cancers. Methods: Capecitabine was given at 725 mg/m2 orally twice daily Monday through Friday concurrently with RT. Oxaliplatin was given intravenously at 50 mg/m2 once weekly five times starting the first day of RT. The radiation dose was 50.4 Gy in 28 fractions (1.8 Gy/fraction), five fractions weekly. Endorectal tumor biopsies were obtained before treatment and on the third day of treatment to explore the effects of treatment on thymidine phosphorylase, thymidylate synthase, excision repair cross-complementing rodent repair deficiency complementation group 1 (ERCC1), and apoptosis. Results: A total of 25 patients were enrolled in this study; 6 patients (24%) had a complete pathologic response. T-downstaging occurred in 52% of patients, and N-downstaging occurred in 53%. Grade 3 diarrhea was the most common Grade 3-4 toxicity, occurring in 20% of patients. Only 2 patients experienced disease recurrence, with a median of 20 months of follow-up. Thymidylate synthase, thymidine phosphorylase, ERCC1, and apoptosis did not vary significantly between the pretreatment and Day 3 tumor biopsies, nor did they predict for T-downstaging or a complete pathologic response. Conclusion: Capecitabine at 725 mg/m2 orally twice daily, oxaliplatin 50 mg/m2/wk, and RT at 50.4 Gy is an effective neoadjuvant combination for Stage II and III rectal cancer and results in a greater rate of complete pathologic responses than historically shown in fluoropyrimidine plus RT controls.
AB - Purpose: To evaluate the efficacy of a combination of capecitabine, oxaliplatin, and radiotherapy (RT) in the neoadjuvant treatment of Stage II and III rectal cancers. Methods: Capecitabine was given at 725 mg/m2 orally twice daily Monday through Friday concurrently with RT. Oxaliplatin was given intravenously at 50 mg/m2 once weekly five times starting the first day of RT. The radiation dose was 50.4 Gy in 28 fractions (1.8 Gy/fraction), five fractions weekly. Endorectal tumor biopsies were obtained before treatment and on the third day of treatment to explore the effects of treatment on thymidine phosphorylase, thymidylate synthase, excision repair cross-complementing rodent repair deficiency complementation group 1 (ERCC1), and apoptosis. Results: A total of 25 patients were enrolled in this study; 6 patients (24%) had a complete pathologic response. T-downstaging occurred in 52% of patients, and N-downstaging occurred in 53%. Grade 3 diarrhea was the most common Grade 3-4 toxicity, occurring in 20% of patients. Only 2 patients experienced disease recurrence, with a median of 20 months of follow-up. Thymidylate synthase, thymidine phosphorylase, ERCC1, and apoptosis did not vary significantly between the pretreatment and Day 3 tumor biopsies, nor did they predict for T-downstaging or a complete pathologic response. Conclusion: Capecitabine at 725 mg/m2 orally twice daily, oxaliplatin 50 mg/m2/wk, and RT at 50.4 Gy is an effective neoadjuvant combination for Stage II and III rectal cancer and results in a greater rate of complete pathologic responses than historically shown in fluoropyrimidine plus RT controls.
KW - Capecitabine
KW - Chemoradiotherapy
KW - Oxaliplatin
KW - Phase II
KW - Rectal cancer
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U2 - 10.1016/j.ijrobp.2008.01.020
DO - 10.1016/j.ijrobp.2008.01.020
M3 - Article
C2 - 18565686
AN - SCOPUS:52949095388
SN - 0360-3016
VL - 72
SP - 650
EP - 657
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 3
ER -