Combined preoperative radiation and mitomycin/5-fluorouracil treatment for locally advanced rectal adenocarcinoma

537 Background: Treatment for locally advanced rectal cancer (LARC) includes preoperative radiation concurrent with fluoropyrimidine chemotherapy (CRT). Local recurrence is a problem. Cetuximab is active in colorectal cancer and is effective with radiotherapy in other diseases. This study evaluated the pathologic response rate for LARC treated with preoperative chemoradiotherapy w/wo cetuximab. Methods: LARC (T3/4 or LN+, M0) pts were randomized to Arm1/Arm2. Arm 1 received standard pelvic radiotherapy (5040-5400cGy in daily fractions) with continuous infusional 5-FU (225mg/m2/day); Arm 2 received identical chemoradiotherapy + concurrent cetuximab (400mg/m2 initial dose) 1 week before pelvic radiotherapy, followed by 250mg/m2 weekly for the duration of chemoradiotherapy. After study treatment completion, pts were re-evaluated clinically and radiographically for clinical response. After 6-8 weeks, patients underwent surgical resection. The primary end point was pathologic CR (pCR), and secondary endpoints included ORR, RFS, OS, and local recurrence rates. Results: 139 pts were enrolled (Arm 1=69/Arm2=70); Arm1/Arm2 median age 61/55 yrs, and stage II and III 59%, 39%/40%, 60%. In 124 postsurgery pts, pCR occurred in 17 Arm 1 pts (28.3%, 95% CI 17.5-41.4) and 17 Arm 2 pts (26.6%, 95% CI 16.3-39.1); TRG postsurgery was similar between treatment arms (Table). Grade 3 and 4 toxicities were largely nonhematologic: diarrhea 16%/22%, rash 0%/12%, dehydration 5%/8%, mucositis 5%/6%. The 5-yr RFS for Arm1/Arm2 was 61%/65%, 5-yr OS was 66%/83%, local recurrence was 3%/4%. Conclusions: The addition of cetuximab to preoperative CRT for LARC was associated with increased but manageable toxicities. pCR rates were similar between treatment arms, as were survival statistics and local recurrence rates. No association was found between KRAS status and pCR. Clinical trial information: NCT00527111. [Table: see text]

Download Full-text

Phase-2 study of neoadjuvant chemoradiation in locally advanced rectal adenocarcinoma: The Radio-Xelox study

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.13549 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 13549-13549 ◽

Cited By ~ 2

Author(s):

M. Salimichokami ◽

M. Vafai ◽

S. Derakhshani ◽

S. Aminian ◽

A. A. Vaheed

Keyword(s):

Radiation Treatment ◽

Locally Advanced ◽

Rectal Adenocarcinoma ◽

Neoadjuvant Chemoradiation ◽

Severe Adverse Effect ◽

Preoperative Radiation ◽

Systemic Spread ◽

Phase 2 Study ◽

Grade 3 ◽

Pathologic Complete Remission

13549 Background: Neoadjuvant Radiation treatment has been shown in many studies to decrease the incidence of loco-regional relapse in pts with locally-advanced Rectal Adenocarcinoma. Capecitabine and Oxaliplatin are both effective antineoplastic drugs in Colorectal Adenocarcinoma. They also have radiosensitizing effects. Hence,it is rational to combine these agents in association with radiotherapy,to achieve local controle and prevent systemic spread of the cancer. Methods: Thirty-eight pts with Rectal Adenocarcinoma (T3-T4 and/or N+) received radiation treatment (2.0 Gy, 5days a wk over 5 wks,total dose 50 Gy) plus oral Capecitabine at 600 mg/m2 twice a day and iv Oxaliplatin at 35 mg/m2 once weekly × 5wks. Surgery was performed 6wks post completion of XRT. Our end points were safety/feasibility and response/efficacy as demonstrable by the rate of pathologic complete remission (path-CR). Results: Seven pts (20%) acheived path-CR. Diarrhea was the most important severe adverse effect (in 25% of pts). fourteen pts (40%) showed good regression (very few cancer cells in fibronecrotic tissue Dworak grade 3). The remaining 17 pts showed less favorable regression or no significant change. Conclusions: Preoperative Radiation treatment plus chemotherapy with XELOX regimen is feasible, safe and effective with an impressive rate of path-CR in locoregionally advanced Rectal Adenocarcinoma. No significant financial relationships to disclose.

Download Full-text