Neoadjuvant Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Radiation for Rectal Cancer

• Published in: International journal of radiation oncology, biology, physics Vol. 82; no. 1; pp. 124 - 129
• Main Authors: Dipetrillo, Tom, M.D, Pricolo, Victor, M.D, Lagares-Garcia, Jorge, M.D, Vrees, Matt, M.D, Klipfel, Adam, M.D, Cataldo, Tom, M.D, Sikov, William, M.D, McNulty, Brendan, M.D, Shipley, Joshua, M.D, Anderson, Elliot, M.D, Khurshid, Humera, M.D, Oconnor, Brigid, M.D, Oldenburg, Nicklas B.E., M.D, Radie-Keane, Kathy, M.D, Husain, Syed, M.D, Safran, Howard, M.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 2012; Elsevier
• Subjects: 5-Fluorouracil; ABSCESSES; Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Adenocarcinoma - radiotherapy; Adenocarcinoma - surgery; Adult; Aged; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - adverse effects; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Biological and medical sciences; CITROVORUM FACTOR; DIARRHEA; Diarrhea - etiology; DOSES; Drug Administration Schedule; Early Termination of Clinical Trials; Feasibility Studies; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Gastroenterology. Liver. Pancreas. Abdomen; HEALING; Hematology, Oncology and Palliative Medicine; Humans; Induction Chemotherapy - adverse effects; Induction Chemotherapy - methods; INFUSION; Leucovorin - administration & dosage; Leucovorin - adverse effects; Male; Medical sciences; Middle Aged; Neoadjuvant; Neoadjuvant Therapy - adverse effects; Neoadjuvant Therapy - methods; NEOPLASMS; Neutropenia - etiology; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - adverse effects; Oxaliplatin; PAIN; Pain - etiology; PATIENTS; Postoperative Complications - etiology; Prospective Studies; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; Radiotherapy Dosage; Rectal cancer; Rectal Neoplasms - drug therapy; Rectal Neoplasms - pathology; Rectal Neoplasms - radiotherapy; Rectal Neoplasms - surgery; RECTUM; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; SURGERY; TOXICITY; Tumors; URACILS; WOUNDS; Neoadjuvant; Oxaliplatin; Rectal cancer; Bevacizumab; Antineoplastic agent; Rectal disease; Monoclonal antibody; Neoadjuvant treatment; Cancerology; Intestinal disease; Antiangiogenic agent; Anorectal disease; Platinum II Complexes; Fluorouracil; Enzyme; Fluoropyrimidine derivatives; Transferases; Enzyme inhibitor; Malignant tumor; Rectum cancer; Thymidylate synthase; Immunomodulator; Alkylating agent; Vascular endothelium growth factor; Antimetabolic; Methyltransferases; Pyrimidine derivatives; Digestive diseases; Cancer
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2010.08.005

Purpose To evaluate the feasibility and pathologic complete response rate of induction bevacizumab + modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen followed by concurrent bevacizumab, oxaliplatin, continuous infusion 5-fluorouracil (5-FU), and radiation for patients with rectal cancer. Methods and Materials Eligible patients received 1 month of induction bevacizumab and mFOLFOX6. Patients then received 50.4 Gy of radiation and concurrent bevacizumab (5 mg/kg on Days 1, 15, and 29), oxaliplatin (50 mg/m2 /week for 6 weeks), and continuous infusion 5-FU (200 mg/m2 /day). Because of gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m2 /week. Resection was performed 4−8 weeks after the completion of chemoradiation. Results The trial was terminated early because of toxicity after 26 eligible patients were treated. Only 1 patient had significant toxicity (arrhythmia) during induction treatment and was removed from the study. During chemoradiation, Grade 3/4 toxicity was experienced by 19 of 25 patients (76%). The most common Grade 3/4 toxicities were diarrhea, neutropenia, and pain. Five of 25 patients (20%) had a complete pathologic response. Nine of 25 patients (36%) developed postoperative complications including infection ( n = 4), delayed healing ( n = 3), leak/abscess ( n = 2), sterile fluid collection ( n = 2), ischemic colonic reservoir ( n = 1), and fistula ( n = 1). Conclusions Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU, and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen was similar to other fluorouracil chemoradiation regimens. The high incidence of postoperative wound complications is concerning and consistent with other reports utilizing bevacizumab with chemoradiation before major surgical resections.