A phase II study of capecitabine (CAP) and pre-operative radiation therapy (RT) in resectable, locally advanced rectal cancer (LARC)

Abstract

3540 Background: Preoperative RT with c.i. 5-fluorouracil (5-FU) improves local tumor control, sphincter preservation, and yields pathologic complete remissions (pCR) in 10–30% of patients (pts) with LARC. Capecitabine (CAP) is an oral fluoropyrimidine which is converted into 5-FU preferentially in tumor cells by the high intra-tumor activity of thymidine phosphorylase (TP). TP can be further up-regulated by RT. Moreover, CAP may mimic c.i. 5-FU via daily oral administration thus simplifying chemoradiation. Methods: Based on phase I data (Dunst et al., JCO 20:3983, 2002) a multicentric phase II study of CAP (825 mg/m2, twice daily, 7 days/week) with RT (45 Gy/ 25 fr. to the posterior pelvis followed by 5.4 Gy / 3 fr. boost to the tumor) was planned in resectable, LARC. Patients (pts) with T3 or T4, N0 or N1–2 disease were eligible. Surgery was scheduled 6 weeks after the end of CAP-RT and 4-month adjuvant CAP was also provided based on physician indications. The primary endpoint was to determine the pCR rate and secondary endpoints were to assess clinical response rate and safety profile of CAP-RT combination. Results: From September 2001 to July 2003, 53 pts (median age: 63yrs; ECOG-PS 0–1; M/F: 39/14) with T3 N0–2 (87%) and T4 N0–2 (13%) disease entered the study. All pts but 2 completed the RT as planned whereas 7 pts did not receive the entire planned dose of CAP because of toxicity (G 2–3 leukopenia, G 2–3 cystitis, G 2–3 skin toxicity). Overall, all the 53 pts are evaluable for clinical response and safety, whereas 51 pts are evaluable for pathologic response and downstaging (1 pt refused surgery, 1 pt was unresectable at operation). Complete or partial clinical response was 58% (31/53 pts) and tumor downstaging 57% (29/51 pts) with 12 pCR (24%). The most common adverse events were G 1–2 leukopenia, diarrhea, proctitis, occurring in 72%, 42% and 34% of pts, respectively; only 6 pts (11%) had G3 toxicity. No G4 toxicity was reported. Conclusions: chemoradiation with CAP and pre-op RT appeared to be effective and well tolerated and it could replace c.i. 5-FU in LARC. Its favourable safety profile support a possible combination with other effective drugs. No significant financial relationships to disclose.