Phase II Trial of Neoadjuvant Bevacizumab, Capecitabine, and Radiotherapy for Locally Advanced Rectal Cancer

• Published in: International journal of radiation oncology, biology, physics Vol. 76; no. 3; pp. 824 - 830
• Main Authors: Crane, Christopher H., Eng, Cathy, Feig, Barry W., Das, Prajnan, Skibber, John M., Chang, George J., Wolff, Robert A., Krishnan, Sunil, Hamilton, Stanley, Janjan, Nora A., Maru, Dipen M., Ellis, Lee M., Rodriguez-Bigas, Miguel A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2010
• Subjects: Acute toxicity; Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; ANTINEOPLASTIC DRUGS; Bevacizumab; BIOLOGICAL RECOVERY; BODY; Capecitabine; Chemoradiation; Chemotherapy, Adjuvant - methods; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; DIGESTIVE SYSTEM; DISEASES; Dose Fractionation, Radiation; DRUGS; Female; Fluorouracil - administration & dosage; Fluorouracil - analogs & derivatives; Follow-Up Studies; GASTROINTESTINAL TRACT; HEALING; Hematology, Oncology and Palliative Medicine; Humans; INJURIES; INTESTINES; LARGE INTESTINE; Male; MEDICINE; Middle Aged; Neoadjuvant; Neoadjuvant Therapy - adverse effects; Neoadjuvant Therapy - methods; Neoplasm Staging; NEOPLASMS; NUCLEAR MEDICINE; ORGANS; RADIOLOGY; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; Rectal cancer; Rectal Neoplasms - drug therapy; Rectal Neoplasms - pathology; Rectal Neoplasms - radiotherapy; Rectal Neoplasms - surgery; RECTUM; SURGERY; Surgical Wound Dehiscence - chemically induced; THERAPY; TOXICITY; WOUNDS; Neoadjuvant; Rectal cancer; Chemoradiation; Bevacizumab
• ISSN: 0360-3016; 1879-355X; 1879-355X
• DOI: 10.1016/j.ijrobp.2009.02.037

We designed this Phase II trial to assess the efficacy and safety of the addition of bevacizumab to concurrent neoadjuvant capecitabine-based chemoradiation in locally advanced rectal cancer. Between April 2004 and December 2007, 25 patients with clinically staged T3N1 ( n = 20) or T3N0 ( n = 5) rectal cancer received neoadjuvant therapy with radiotherapy (50.4 Gy in 28 fractions over 5.5 weeks), bevacizumab every 2 weeks (3 doses of 5 mg/kg), and capecitabine (900 mg/m 2 orally twice daily only on days of radiation), followed by surgical resection a median of 7.3 weeks later. Procedures included abdominoperineal resection (APR; 6 patients), proctectomy with coloanal anastamosis (8 patients), low anterior resection (10 patients), and local excision (1 patient). Eight (32%) of 25 patients had a pathologic complete response, and 6 (24%) of 25 had <10% viable tumor cells in the specimen. No patient had Grade 3 hand-foot syndrome, gastrointestinal toxicity, or significant hematologic toxicity. Three wound complications required surgical intervention (one coloanal anastamostic dehiscence requiring completion APR and two perineal wound dehiscences after initial APR). Five minor complications occurred that resolved without operative intervention. With a median follow-up of 22.7 months (range, 4.5–32.4 months), all patients were alive; one patient has had a recurrence in the pelvis (2-year actuarial rate, 6.2%) and 3 had distant recurrences. The addition of bevacizumab to neoadjuvant chemoradiation resulted in encouraging pathologic complete response without an increase in acute toxicity. The impact of bevacizumab on perineal wound and anastamotic healing due to concurrent bevacizumab requires further study.