Four-Week Neoadjuvant Intensity-Modulated Radiation Therapy With Concurrent Capecitabine and Oxaliplatin in Locally Advanced Rectal Cancer Patients: A Validation Phase II Trial

• Published in: International journal of radiation oncology, biology, physics Vol. 83; no. 2; pp. 587 - 593
• Main Authors: Arbea, Leire, Martínez-Monge, Rafael, Díaz-González, Juan A., Moreno, Marta, Rodríguez, Javier, Hernández, Jose Luis, Sola, Jesús Javier, Ramos, Luis Isaac, Subtil, Jose Carlos, Nuñez, Jorge, Chopitea, Ana, Cambeiro, Mauricio, Gaztañaga, Miren, García-Foncillas, Jesús, Aristu, Javier
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2012; Elsevier
• Subjects: Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adenocarcinoma - therapy; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Capecitabine; Chemoradiotherapy - adverse effects; Chemoradiotherapy - methods; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; DIARRHEA; Diarrhea - etiology; Dose Fractionation; Drug Administration Schedule; Female; Fluorouracil - administration & dosage; Fluorouracil - analogs & derivatives; Gastroenterology. Liver. Pancreas. Abdomen; Hematology, Oncology and Palliative Medicine; Humans; Intensity-modulated radiation therapy; Locally advanced rectal cancer; Male; Medical sciences; Middle Aged; Neoadjuvant Therapy - adverse effects; Neoadjuvant Therapy - methods; Neoplasm Staging; NEOPLASMS; Organoplatinum Compounds - administration & dosage; Oxaliplatin; Pathological response; Patient Compliance; PATIENTS; POLYMERASE CHAIN REACTION; Preoperative Care - methods; PROCTITIS; Proctitis - etiology; Proctitis - pathology; RADIATION DOSES; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; Radiotherapy, Intensity-Modulated - adverse effects; Radiotherapy, Intensity-Modulated - methods; Rectal Neoplasms - mortality; Rectal Neoplasms - pathology; Rectal Neoplasms - therapy; RECTUM; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; SURGERY; TOXICITY; Treatment Outcome; Tumors; VALIDATION; Intensity-modulated radiation therapy; Pathological response; Locally advanced rectal cancer; Oxaliplatin; Capecitabine; Antineoplastic agent; Rectal disease; Concurrent; Neoadjuvant treatment; Cancerology; Phase II trial; Intestinal disease; Pyrimidine nucleoside; Anorectal disease; Platinum II Complexes; Human; Validation; Fluoropyrimidine derivatives; Malignant tumor; Rectum cancer; Prodrug; Alkylating agent; Intensity modulated radiotherapy; Digestive diseases; Locally advanced stage; Cancer
• ISSN: 0360-3016; 1879-355X; 1879-355X
• DOI: 10.1016/j.ijrobp.2011.06.2008

To validate tolerance and pathological complete response rate (pCR) of a 4-week preoperative course of intensity-modulated radiation therapy (IMRT) with concurrent capecitabine and oxaliplatin (CAPOX) in patients with locally advanced rectal cancer. Patients with T3 to T4 and/or N+ rectal cancer received preoperative IMRT (47.5 Gy in 19 fractions) with concurrent capecitabine (825 mg/m2 b.i.d., Monday to Friday) and oxaliplatin (60 mg/m2 on Days 1, 8, and 15). Surgery was scheduled 4 to 6 weeks after the completion of chemoradiation. Primary end points were toxicity and pathological response rate. Local control (LC), disease-free survival (DFS), and overall survival (OS) were also analyzed. A total of 100 patients were evaluated. Grade 1 to 2 proctitis was observed in 73 patients (73%). Grade 3 diarrhea occurred in 9% of the patients. Grade 3 proctitis in 18% of the first 50 patients led to reduction of the dose per fraction to 47.5 Gy in 20 treatments. The rate of Grade 3 proctitis decreased to 4% thereafter (odds ratio, 0.27). A total of 99 patients underwent surgery. A pCR was observed in 13% of the patients, major response (96–100% of histological response) in 48%, and pN downstaging in 78%. An R0 resection was performed in 97% of the patients. After a median follow-up of 55 months, the LC, DFS, and OS rates were 100%, 84%, and 87%, respectively. Preoperative CAPOX-IMRT therapy (47.5 Gy in 20 fractions) is feasible and safe, and produces major pathological responses in approximately 50% of patients.