Phase II Study of Weekly Intravenous Oxaliplatin Combined With Oral Daily Capecitabine and Radiotherapy With Biologic Correlates in Neoadjuvant Treatment of Rectal Adenocarcinoma

Journal Article · Sat Nov 01 04:00:00 EDT 2008 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2008.01.020· OSTI ID:21128192

BullardDunn, Kelli ^[1]; Yang, Gary Y ^[2]; Pendyala, Lakshmi ^[3]; Toth, Karoly ^[4]; Andrews, Chris ^[5]; Rustum, Youcef M ^[3]; Ross, Mary Ellen ^[6]; LeVea, Charles ^[7]; Puthillath, Ajithkumar ^[8]; Park, Young-Mee ^[9]; Rajput, Ashwani ^[1]

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1. Department of Surgery, Roswell Park Cancer Institute, Buffalo, NY (United States)
2. Department of Radiation Oncology, Roswell Park Cancer Institute, Buffalo, NY (United States)
3. Department of Oncology, Roswell Park Cancer Institute, Buffalo, NY (United States)
4. Department of Pharmacology, Roswell Park Cancer Institute, Buffalo, NY (United States)
5. Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, NY (United States)
6. Research Coordinator, Roswell Park Cancer Institute, Buffalo, NY (United States)
7. Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY (United States)
8. Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY (United States)
9. Department of Stress Biology, Roswell Park Cancer Institute, Buffalo, NY (United States)

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/m{sup 2} orally twice daily Monday through Friday concurrently with RT. Oxaliplatin was given intravenously at 50 mg/m{sup 2} 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/m{sup 2} orally twice daily, oxaliplatin 50 mg/m{sup 2}/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.

• OSTI ID: 21128192
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 3 Vol. 72; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
APOPTOSIS
BIOPSY
CARCINOMAS
COMBINED THERAPY
DIARRHEA
EXCISION REPAIR
PATIENTS
RADIATION DOSES
RADIOTHERAPY
RECTUM
RODENTS
THYMIDINE
TOXICITY