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.
NEOADJUVANT CHEMORADIATION THERAPY WITH CAPECITABINE (CAP) PLUS OXALIPLATIN IN RECTAL CANCER: FINAL RESULTS OF A PHASE II STUDY.
PEPE, Stefano
2008-01-01
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
