BACKGROUND: Recent studies have demonstrated the feasibility of combining oxaliplatin with 5-fluorouracil (5-FU) or capecitibine and radiation therapy. The addition of bevacizumab to chemotherapy improves overall survival for metastatic disease. We initiated a phase 2 trial to evaluate preoperative capecitabine, oxaliplatin, and bevacizumab with radiation therapy followed by surgery and postoperative 5-FU, leucovorin, oxaliplatin (FOLFOX) and bevacizumab for locally advanced rectal cancer. METHODS: Fifty-seven patients with resectable T3/T4 rectal adenocarcinoma were enrolled. Preoperative treatment was capecitabine (825 mg/m(2) twice daily from Monday to Friday), oxaliplatin (50 mg/m(2) weekly), bevacizumab (5 mg/kg on days 1, 15, 29), and radiation therapy (50.4 Gy). Surgery was performed by 6 weeks after neoadjuvant therapy. Beginning 8 to 12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) every 2 weeks for 12 cycles. RESULTS: Fifty-four of 57 enrolled patients were eligible. Forty-nine (91%) patients completed preoperative therapy and underwent surgery. Nine patients (17%; 90% confidence interval, 9%-27%) achieved pathologic complete response. Thirty-two patients (59%) experienced pathologic tumor downstaging, and 53% and 15% of patients experienced worst grade 3 and grade 4 acute toxicity, respectively. Forty-seven percent of patients who underwent surgery experienced a surgical complication. CONCLUSIONS: The primary endpoint of a 30% pathologic complete response rate was not reached; however, the majority of patients experienced pathologic downstaging with this regimen. Increased wound-healing delays and complications may have been related to the addition of bevacizumab, oxaliplatin, or both. Continued observation of these patients will establish the long-term morbidity and efficacy of this combined modality approach.
BACKGROUND: Recent studies have demonstrated the feasibility of combining oxaliplatin with 5-fluorouracil (5-FU) or capecitibine and radiation therapy. The addition of bevacizumab to chemotherapy improves overall survival for metastatic disease. We initiated a phase 2 trial to evaluate preoperative capecitabine, oxaliplatin, and bevacizumab with radiation therapy followed by surgery and postoperative 5-FU, leucovorin, oxaliplatin (FOLFOX) and bevacizumab for locally advanced rectal cancer. METHODS: Fifty-seven patients with resectable T3/T4 rectal adenocarcinoma were enrolled. Preoperative treatment was capecitabine (825 mg/m(2) twice daily from Monday to Friday), oxaliplatin (50 mg/m(2) weekly), bevacizumab (5 mg/kg on days 1, 15, 29), and radiation therapy (50.4 Gy). Surgery was performed by 6 weeks after neoadjuvant therapy. Beginning 8 to 12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) every 2 weeks for 12 cycles. RESULTS: Fifty-four of 57 enrolled patients were eligible. Forty-nine (91%) patients completed preoperative therapy and underwent surgery. Nine patients (17%; 90% confidence interval, 9%-27%) achieved pathologic complete response. Thirty-two patients (59%) experienced pathologic tumor downstaging, and 53% and 15% of patients experienced worst grade 3 and grade 4 acute toxicity, respectively. Forty-seven percent of patients who underwent surgery experienced a surgical complication. CONCLUSIONS: The primary endpoint of a 30% pathologic complete response rate was not reached; however, the majority of patients experienced pathologic downstaging with this regimen. Increased wound-healing delays and complications may have been related to the addition of bevacizumab, oxaliplatin, or both. Continued observation of these patients will establish the long-term morbidity and efficacy of this combined modality approach.
Authors: Frank A Scappaticci; Louis Fehrenbacher; Thomas Cartwright; John D Hainsworth; William Heim; Jordan Berlin; Fairooz Kabbinavar; William Novotny; Somnath Sarkar; Herbert Hurwitz Journal: J Surg Oncol Date: 2005-09-01 Impact factor: 3.454
Authors: In Ja Park; Y Nancy You; Atin Agarwal; John M Skibber; Miguel A Rodriguez-Bigas; Cathy Eng; Barry W Feig; Prajnan Das; Sunil Krishnan; Christopher H Crane; Chung-Yuan Hu; George J Chang Journal: J Clin Oncol Date: 2012-04-09 Impact factor: 44.544
Authors: C G Lee; M Heijn; E di Tomaso; G Griffon-Etienne; M Ancukiewicz; C Koike; K R Park; N Ferrara; R K Jain; H D Suit; Y Boucher Journal: Cancer Res Date: 2000-10-01 Impact factor: 12.701
Authors: Herbert Hurwitz; Louis Fehrenbacher; William Novotny; Thomas Cartwright; John Hainsworth; William Heim; Jordan Berlin; Ari Baron; Susan Griffing; Eric Holmgren; Napoleone Ferrara; Gwen Fyfe; Beth Rogers; Robert Ross; Fairooz Kabbinavar Journal: N Engl J Med Date: 2004-06-03 Impact factor: 91.245
Authors: Prajnan Das; Cathy Eng; Miguel A Rodriguez-Bigas; George J Chang; John M Skibber; Y Nancy You; Dipen M Maru; Mark F Munsell; Marilyn V Clemons; Scott E Kopetz; Christopher R Garrett; Imad Shureiqi; Marc E Delclos; Sunil Krishnan; Christopher H Crane Journal: Int J Radiat Oncol Biol Phys Date: 2013-12-05 Impact factor: 7.038
Authors: Jerome C Landry; Yang Feng; Steven J Cohen; Charles A Staley; Richard Whittington; Elin Ruth Sigurdson; Halla Nimeiri; Udit Verma; Roshan S Prabhu; Al Bowen Benson Journal: Cancer Date: 2013-01-03 Impact factor: 6.860