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Randomized Phase II Study of Neoadjuvant Combined-Modality Chemoradiation for Distal Rectal Cancer: Radiation Therapy Oncology Group Trial 0012

From the Geisinger Cancer Institute, Wilkes-Barre; Radiation Therapy Oncology Group Headquarters; Thomas Jefferson University, Philadelphia; Reading Hospital and Medical Center, Reading, PA; University of Maryland Medical Center, Department of Surgical Oncology, Baltimore, MD; Bay Medical Regional Cancer Center, Panama City, FL; Ingalls Memorial Hospital, Harvey, IL; Santa Fe Cancer Center, Santa Fe, NM; and Duke University Medical Center, Durham, NC

Address reprint requests to Mohammed Mohiuddin, MD, Geisinger Cancer Institute, 100 E Mountain Blvd, MC 34-66, Wilkes-Barre, PA 18711; e-mail: mmohiuddin1{at}geisinger.edu

PURPOSE: To evaluate the rate of pathologic complete response and toxicity of neoadjuvant chemoradiation for advanced T3/T4 distal rectal cancers in a randomized phase II study

PATIENTS AND METHODS: Patients with clinical T3/T4 distal rectal cancers were randomly assigned in a phase II study to receive combined neoadjuvant chemoradiotherapy followed by surgical resection. Patients were randomly assigned to receive continuous venous infusion (CVI) fluorouracil (FU) 225 mg/m² per day, 7 days per week, plus pelvic hyperfractionated radiation 55.2 to 60 Gy at 1.2 Gy bid (arm 1) or CVI FU 225 mg/m² per day Monday to Friday, 120 hours per week plus irinotecan 50 mg/m² once weekly for 4 weeks plus pelvic radiation therapy 50.4 to 54 Gy at 1.8 Gy per day (arm 2). Surgery was performed 4 to 10 weeks after completion of neoadjuvant therapy. The primary end point of this study was pathologic complete response (pCR). Secondary end points included acute and late normal tissue morbidity.

RESULTS: A total of 106 patients were entered onto the study, with 103 assessable for response. The overall resectability rate was 93%. The median time to surgery was 7 weeks. Tumor downstaging was observed in 78% of patients in both arms. The pCR rate for all assessable patients was 26% in each arm. For patients who had surgery, the pCR rate was also the same (28%) in both arms. Acute and late toxicity was also similar. Grade 3 and 4 acute hematologic and nonhematologic toxicity occurred in 13% and 38% in arm 1 and 12% and 45% in arm 2, respectively.

CONCLUSION: Although the overall complete response rate and toxicity seems similar in both arms, this is the first multi-institutional study to establish a relatively high (28%) pCR rate after neoadjuvant therapy.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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