5-fluorouracil, leucovorin and oxaliplatin (FOLFOX4) as postoperative adjuvant chemotherapy (CT) for node positive rectal cancer after radiochemotherapy (R-CT) and surgery

Aims: To evaluate the activity and safety of postoperative adjuvant CT of 8 cycles FOLFOX4 in patients with node-positive rectal cancer after neoadjuvant R-CT and surgery.

Methods: We included 41 pts with preoperative node positive adenocarcinoma of the rectum (inferior margin within 12cm from the anal verge) and no evidence of distant metastases (cT1–4 N+ M0) into this prospective single center study. The preoperative R-CT treatment consisted of 50.4Gy (1.8Gy per day, five days per week) and 5-fluorouracil, given in a 120-hour continuous intravenous infusion at a dose of 1000mg/m² per day during the first and fifth week. Surgery (total mesorectal excision) was scheduled 4 to 6 weeks after the completion of R-CT. 4 to 6 weeks after surgery 8 cycles of FOLFOX4 were administered (oxaliplatin 85mg/m2 on day 1, leucovorin 200mg/m2 per day 1 + 2 followed by 5-fluorouracil bolus of 400mg/m2 and then 22h infusion of 600mg/m2 on day 1 + 2; repeated day 15). The main end points were feasibility and activity of postoperative CT with FOLFOX4.

Results: From 5/2006 to 11/2008 a total of 41 pts with cT1–4 N+ M0 rectal cancer were included. Median age was 66yrs (range 38–80). 7 of 41 pts (17%) did not receive postoperative FOLFOX4 therapy because of patient refusal (n=3), contraindication to oxaliplatin (n=1) or complications prior to start of FOLFOX4 (n=3). 34 of 41 pts (83%) received postoperative CT with FOLFOX4. Of these 34 pts 15 (44%) completed all 8 cycles FOLFOX4 with 100% dose intensity. 15 pts (44%) received less than 100% but more than 50% of FOLFOX4 dose intensity. No grade 3 or 4 toxicities were observed. Grade 1 or 2 leucopenia occurred in 6 of 34 pts (18%), but no infection or febrile episode was observed. 1 of 34 pts (3%) experienced grade 2 and 15 of 34 pts (44%) grade 1 sensory neuropathy. Sensory neuropathy was the main cause of dose modification of oxaliplatin. After a median follow up of 26 months 3 of 34 pts (9%) had a cancer recurrence (local n=1, local/distant n=1, distant n=1).

Conclusions: Postoperative adjuvant CT with 8 cycles FOLFOX4 is a well tolerated and effective treatment for patients with node positive rectal cancer after R-CT and surgery.