NEOADJUVANT CHEMORADIATION THERAPY WITH CAPECITABINE (CAP) PLUS OXALIPLATIN IN RECTAL CANCER: FINAL RESULTS OF A PHASE II STUDY.

Background: Pre-operative chemoradiation is nowadays a standard treatment for rectal cancer patients (pts). CAP plus OX (CAP-OX) are synergistic with radiotherapy (RT) and active in colorectal neoplasms. Methods: Two cycles of CAP 825 mg/sqm bid (days 1–14) and OX 50 mg/sqm (days 1 & 8) every 3 weeks were given concomitantly with pelvic conformal RT (1.8 Gy daily up to 45 Gy in 5 weeks). Pts were eligible if they had a T3 rectal mass (as measured by endorectal ultrasound) or involved peri-rectal lymph-nodes (uN+). The pathologic tumor response was defined according to the Tumor Regression Grade (TRG) scale. A 2-steps design for phase II trials was adopted: 18 pts ( 3 TRG1) for first step and a total of 43 pts ( 8 TRG1) were estimated to meet the primary endpoint that was the activity of preoperative RT plus CAP-OX on TRG. Results: As of July ‘07, 45 pts were enrolled (29 M, 16 F) with a median age of 64.4 years (range 42–79). All pts completed the neoadjuvant chemoradiotherapy program and are evaluable for toxicity: G1–2 gastrointestinal adverse events were observed in 25 pts; only 1 pt experienced G3 vomiting and 1 pt G3 diarrhea; 7 pts had G1 peripheral neuropathy. Hematological toxicity (G1-G2) was observed in 6 pts. Local toxicity (G1) was experienced by 22 pts; G2 proctitis and anal pain occurred in only 2 pts. After treatment the uT3-uT4 rate was 68.7% (versus 88.8% before) and only 25.8% of pts were uN+ (versus 57.7% before treatment). 42 pts have been operated (1 refused surgery, 1 developed lung metastases and 1 deceased for reasons other than toxicity or tumor progression): low anterior resection was performed in 29 pts (69%), abdominal perineal resection in 12 pts (28.6%) and transanal resection in 1 pt. Complete pathological response (TRG1) was observed in 10 pts (23.8%); TRG2 in 18 pts (42.9%); TRG3 in 11 pts (26.2%); TRG4 in 3 pts (7.1%). As of Dec 31, 2007, 7 pts recurred: 5 pts with distance metastases (1 peritoneum, 1 brain, 1 nodes, 1 liver, 1 lung); 1 pts with local recurrence; 1 pts with both liver and local recurrence. Conclusions: The combination of CAP-OX with pelvic radiotherapy as pre- operative treatment for rectal cancer is active, producing a remarkable rate of complete or near-complete pathological responses, and overall well tolerated

Predictive factors of response to neoadjuvant chemoradiotherapy in rectal cancer patirnts.

Background: Pre-operative chemo-radiotherapy (CT-RT) produces a high rate of response in rectal cancer patients (pts). Several evidences suggests that using 2 drugs correlates with best responses and that complete pathologic response (cPR) induces prolonged survival. The aim of the present analysis was the evaluation of the effect of some biologic characteristics of the primary tumor on PR, as scored according to Tumor Regression Grade (TRG) scale. Methods: 45 pts, enrolled in a phase II trial, were treated with 2 cycles of CAP-OX concomitantly with pelvic conformal radiotherapy (45 Gy). EGFR, p53, PARP, XRCC, VEGFR and TS expression was determined by immunohistochemistry on rectal biopsies obtained prior CT-RT initiation, and scored as percentage of positive cells. The Spearman’s correlation test, t-test and logistic regression analysis were used to explore the correlation between these biological factors and the TRG (SPSS software). Biological factors expression was considered as a continuous variable. TRG was both considered as 4 categories and coded as TRG1 (cPR) vs TRG >=2. Results: Among the 42 operated pts, cPR (TRG-1) was observed in 10 (23.8%); TRG-2 in 18 (42.9%); TRG-3 in 11 (26.2%); TRG-4 in 3 pts (7.1%). Paraffin embedded biConclusions: A statistically significant inverse association was observed between TRG and TS expression; a weak correlation was suggested between cPR and low EGFR, VEGFR and PARP expression. Neither gender nor age significantly affected cPR.opsies from primary tumor were available for all pts