A phase II study of neoadjuvant chemoradiotherapy with oxaliplatin and capecitabine for rectal cancer.

This study evaluated the efficacy and safety of neoadjuvant chemoradiotherapy with the XELOX regimen in rectal cancer patients. Twenty-five patients with histopathologically confirmed and locally advanced rectal cancer (T3/T4 or N+) were enrolled in the study. Radiotherapy of 5000 cGy was delivered in 25 fractions of 200 cGy five times per week for a total of 5 weeks. During the first, second, fourth and fifth weeks of radiotherapy, the patients also received the following chemotherapy: 50 mg/m2 oxaliplatin on day one and 850 mg/m2 capecitabine bid for 5 days. Surgery was scheduled 5-6 weeks after the completion of the preoperative chemoradiotherapy. Four weeks after the surgery, four more cycles of chemotherapy were administered every 3 weeks. The postoperative chemotherapy consisted of 130 mg/m2 oxaliplatin on day 1 and 1000 mg/m2 capecitabine bid from day 1 to day 14. The end points were the downstage rate, R0 resection rate, and sphincter preservation rate. Twenty-five patients received the neoadjuvant chemoradiotherapy. The overall regression rate was 85%, with a Grade 3/4 regression rate of 30% and a pathological complete response rate of 12%. Among the 17 patients with lower rectal cancer, thirteen (76%) were originally indicated for abdominal-perineal resection (APR). However, after the neoadjuvant chemoradiotherapy, the anus could be preserved in nine patients (53%). The most frequent toxicities of the chemoradiotherapy were diarrhea (64%) and hematological toxicity (60%), followed by nausea and vomiting (48%), urinary tract irritation (28%), and anal pain (24%). Grade 3 or 4 adverse events were relatively infrequent and presented as diarrhea (12%), myelosuppression (8%), and elevated transaminase (4%). Six cases also experienced long-term anal exudates after surgery. Neoadjuvant chemoradiotherapy using the XELOX regimen in rectal cancer patients obviously reduced the TNM staging and improved the pathological complete response rate. The therapy was well-tolerated and had mild adverse events and no serious perioperational complications.

Zhao L ，Bai C ，Shao Y ，Guan M ，Jia N ，Xiao Y ，Qiu H ，Zhang F ，Yang T ，Zhong G ，Chen S ... -  《-》

Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer.

Rödel C ，Liersch T ，Hermann RM ，Arnold D ，Reese T ，Hipp M ，Fürst A ，Schwella N ，Bieker M ，Hellmich G ，Ewald H ，Haier J ，Lordick F ，Flentje M ，Sülberg H ，Hohenberger W ，Sauer R ... -  《-》

Four-week neoadjuvant intensity-modulated radiation therapy with concurrent capecitabine and oxaliplatin in locally advanced rectal cancer patients: a validation phase II trial.

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/m(2) b.i.d., Monday to Friday) and oxaliplatin (60 mg/m(2) 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.

Arbea L ，Martínez-Monge R ，Díaz-González JA ，Moreno M ，Rodríguez J ，Hernández JL ，Sola JJ ，Ramos LI ，Subtil JC ，Nuñez J ，Chopitea A ，Cambeiro M ，Gaztañaga M ，García-Foncillas J ，Aristu J ... -  《-》

Evaluation of capecitabine and oxaliplatin administered prior to and then concomitant to radiotherapy in high risk locally advanced rectal cancer.

Systemic failure remains a predominant issue in locally advanced rectal cancer (LARC). A new strategy using capecitabine and oxaliplatin (XELOX regimen) administered prior to and then concomitant to radiotherapy for high risk LARC is developed in our practice. The aim of the present study was to evaluate the short-term efficacy and toxicities of this strategy. Patients were treated with one cycle XELOX regimen (oxaliplatin 130 mg/m(2) on day 1 with capecitabine 1,000 mg/m(2) twice daily for 14 days every 3 weeks), followed by chemoradiation (50 Gy over 5 weeks) with modified XELOX regimen (oxaliplatin dose reduction to 100 mg/m(2)), and total mesorectal excision. Tumor response, toxicities, and surgical complications were recorded. Forty-two patients treated with the strategy were identified. All patients completed planned dose of induction chemotherapy and concurrent chemoradiotherapy. Grade 3 toxicities were thrombocytopenia (4.8%), diarrhea (7.1%), proctitis (4.8%), and radiation dermatitis (7.1%). Five patients (12.5%) developed postoperative complications. Pathologic complete response (pCR) and nearly pCR were achieved in 7 (15.0%) and 13 patients (35.0%). The preliminary results suggest that induction chemotherapy followed by chemoradiotherapy with capecitabine and oxaliplatin in LARC is well tolerated. The strategy achieves favorable short term outcome in terms of pCR and nearly pCR rate, which warrants further investigation.

Gao YH ，An X ，Sun WJ ，Cai J ，Cai MY ，Kong LH ，Lin JZ ，Liu GC ，Tang JH ，Wu XJ ，Chen G ，Pan ZZ ，Ding PR ... -  《-》

Phase II, randomized study of concomitant chemoradiotherapy followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant chemoradiotherapy and surgery in magnetic resonance imaging-defined, l

Fernández-Martos C ，Pericay C ，Aparicio J ，Salud A ，Safont M ，Massuti B ，Vera R ，Escudero P ，Maurel J ，Marcuello E ，Mengual JL ，Saigi E ，Estevan R ，Mira M ，Polo S ，Hernandez A ，Gallen M ，Arias F ，Serra J ，Alonso V ... -  《-》