Metformin with neoadjuvant chemoradiation to improve pathologic response in rectal cancer: A pilot phase I/II trial.

PURPOSE: Neoadjuvant radiotherapy with or without chemotherapy decreases the risk of local recurrence after surgery for rectal cancer. Emerging data suggest that diabetic patients on metformin may have improved cancer outcome after radiotherapy. A single institutional pilot study was performed to determine if metformin given concurrently with long course chemoradiation (CRT) may improve pathologic complete response (pCR) in non-diabetic rectal cancer patients. The study was designed to construct a confidence interval (CI) for the pCR rate to determine the sample size for a phase 2 trial. METHODS: Non-diabetic patients with biopsy confirmed rectal cancer deemed candidates for long course neoadjuvant CRT were invited to participate. Radiation consisted of 50.4 Gy in 28 daily fractions with concurrent daily capecitabine (825 mg/m2 twice daily). Participants self-administered metformin (500 mg of twice daily) 2 weeks prior to, during and for 4 weeks after CRT. RESULTS: A total of 16 patients were accrued. One patient withdrew from the study. Only grade 1 or 2 adverse events were observed. Three patients had a clinical complete response (cCR) and did not undergo surgery. Of the 12 patients who underwent surgery, there were two pCRs. For the combined pCR/cCR rate of 33% (95% CI 19-47%), a total of 85 patients will be required to yield a 95% CI with a 10% margin of error. CONCLUSIONS: Adding metformin to neoadjuvant CRT for rectal cancer does not appear to enhance toxicities. These results will be used to refine the design and conduct of a future phase 2 trial to determine whether adding metformin to CRT improves pCR/cCR rates.

Neoadjuvant chemoradiotherapy and multivisceral resection for primary locally advanced adherent colon cancer: a single institution experience.

BACKGROUND: Although there is an extensive body of literature on the role of neoadjuvant chemoradiotherapy (CRT) in the management of rectal cancer, its role in primary locally advanced adherent colon cancer (LAACC) is unclear. OBJECTIVE: To analyzed the outcomes of neoadjuvant CRT and multivisceral resection in the management of LAACC patietns. METHODS: We retrospectively reviewed our institutional Colorectal Carcinoma Database for 33 patients with potentially resectable, non-metastatic primary LAACC who received neoadjuvant CRT followed by multivisceral resection. CRT consisted of external beam radiation (45-50 Gy in 25 daily fractions) and concurrent 5-FU infusion (225 mg/m(2)/day). RESULTS: There were 21 males and 12 females. Median age was 64 (31-83) and median follow-up was 36 months. All patients had microscopically clear resection margins (R0). Complete pathologic response was documented in 1 patient (3%) and 66% had ypT4b disease. Post-operative complications were observed in 36% of patients with no 30-day mortality. The 3-year overall survival and 3-year disease-free survival were 85.9% and 73.7% respectively. Two patients developed a local recurrence. CONCLUSIONS: Neoadjuvant CRT and en-bloc multivisceral resection may result in high rates of R0 resection and excellent local control with acceptable morbidity and mortality in selected patients with LAACC.

Reconstructive techniques after rectal resection for rectal cancer.

BACKGROUND: Total mesorectal resection (TME) has led to improved survival and reduced local recurrence in patients with rectal cancer. Straight coloanal anastomosis after TME can lead to problems with frequent bowel movements, fecal urgency and incontinence. The colonic J pouch, side-to-end anastomosis and transverse coloplasty have been developed as alternative surgical strategies in order to improve bowel function. OBJECTIVES: The purpose of this study is to determine which rectal reconstructive technique results in the best postoperative bowel function. SEARCH STRATEGY: A systematic search of the literature (MEDLINE, Cancerlit, Embase and Cochrane Databases) was conducted from inception to Feb 14, 2006 by two independent investigators. SELECTION CRITERIA: Randomized controlled trials in which patients with rectal cancer undergoing low rectal resection and coloanal anastomosis were randomized to at least two different anastomotic techniques. Furthermore, a measure of postoperative bowel function was necessary for inclusion. DATA COLLECTION AND ANALYSIS: Studies identified for potential inclusion were independently assessed for eligibility by at least two reviewers. Data from included trials was collected using a standardized data collection form. Data was collated and qualitatively summarized for bowel function outcomes and meta-analysis statistical techniques were used to pool data on postoperative complications. MAIN RESULTS: Of 2609 relevant studies, 16 randomized controlled trials (RCTs) met our inclusion criteria. Nine RCTs (n=473) compared straight coloanal anastomosis (SCA) to the colonic J pouch (CJP). Up to 18 months postoperatively, the CJP was superior to SCA in most studies in bowel frequency, urgency, fecal incontinence and use of antidiarrheal medication. There were too few patients with long-term bowel function outcomes to determine if this advantage continued after 18 months postop. Four RCTs (n=215) compared the side-to-end anastomosis (STE) to the CJP. These studies showed no difference in bowel function outcomes between these two techniques. Similarly, three RCTs (n=158) compared transverse coloplasty (TC) to CJP. Similarly, there were no differences in bowel function outcomes in these small studies. Overall, there were no significant differences in postoperative complications with any of the anastomotic strategies. AUTHORS' CONCLUSIONS: In several randomized controlled trials, the CJP has been shown to be superior to the SCA in bowel function outcomes in patients with rectal cancer for at least 18 months after gastrointestinal continuity is re-established. The TC and STE anastomoses have been shown to have similar bowel function outcomes when compared to the CJP in small randomized controlled trials; further study is necessary to determine the role of these alternative coloanal anastomotic strategies.