Whitehead, Robert P.

Abstract Background Adjuvant 5-FU monotherapy was previously the standard treatment for stage II/III rectal cancer. This study compared adjuvant FOLFIRI, FOLFOX, and 5-FU/LV. Methods Eligible patients had T3-T4 N0 or Tany N1-3 rectal adenocarcinoma ≤12 cm from the anal verge and received pre-operative or postoperative 5-FU chemoradiotherapy (CRT). Patients were randomized to adjuvant FOLFIRI (8 cycles), FOLFOX (8 cycles), or 5-FU/LV weekly (6/8 weeks; 3 cycles). The trial planned to enroll 3,150 patients but was closed early following activation of an alternative adjuvant rectal cancer study including bevacizumab (E5204). The primary endpoint was overall survival (OS); secondary endpoints included disease-free survival (DFS), sphincter preservation, tolerability, and quality of life (QOL). Results The trial enrolled 225 patients (179 randomized) before early closure. Grade 3/4 toxicity occurred in 59%, with neutropenia, leukopenia, and diarrhea being the most common. At a median follow-up of 9.7 years, no significant OS or DFS differences were observed. The rate of sphincter preservation was numerically higher with FOLFIRI and FOLFOX versus 5-FU/LV, but the difference was not statistically significant. Conclusion FOLFOX and FOLFIRI can be safely administered after CRT in rectal cancer patients safely with expected toxicities. Due to early trial closure and small sample size, the survival analysis was underpowered to detect a significant difference between regimens. ClinicalTrials.gov identifier NCT00068692

e14711 Background: Postoperative adjuvant chemotherapy has been historically limited to single agent 5FU in stage II/III rectal cancer pts. This phase III trial evaluated differences between pts treated with adjuvant FOLFOX versus FOLFIRI versus FU alone in stage II/III rectal cancer. Methods: Eligibility: resectable (T3-4 N0,Tany N1-3) adenocarcinoma rectum ≤12cm from anal verge. Pts had the option to receive FU with pre or postoperative XRT (50.4Gy). Preoperative FU/XRT pts were randomized to adjuvant FOLFIRI (arm A), FOLFOX (arm B), FU/LV(arm C). Postoperative FU/XRT pts were randomized to adjuvant FOLFIRI (arm D), FOLFOX (arm E), FU/LV (arm F). Pts received 8 cycles. Overall survival (OS) was the primary endpoint. Secondary endpoints included toxicity, sphincter preservation and patterns of failure. Results: 225pts out of planned 3150 were enrolled (10/03 to 10/05). Data Monitoring Committee closed E3201 when the GI Intergroup developed an alternative trial with bevacizumab (E5204). 179 pts were randomized; (A:28, B:25, C:30, D:31, E:33, F:32). There was increased grade 3/4 toxicity, mainly diarrhea,in postoperative FU/XRT arms (D:39%), (E:28%), (F:48%). Twenty-two (12%) pts did not receive adjuvant therapy. At a median follow up of 7.4yrs, the five-year recurrence free rate was 69%. Median OS was 8.3 yrs. There was no statistical difference in OS between all randomized groups. Five-year OS in arms (A:B:C:D:E:F) were (73%, 83%, 83%, 73%, 78%, 73%) respectively. Conclusions: FOLFOX can be safely administered to rectal cancer pts following chemo radiation. Given limitations of early trial closure and small sample size, there was no difference in OS between pts who received FU alone, oxaliplatin based or irinotecan based adjuvant therapy. Clinical trial information: NCT00068692.

3526 Background: In the US pts with stage II/III rectal cancer routinely receive pre or postoperative RT/FU. To date, in addition to chemoradiation, standard adjuvant chemotherapy has been limited to single agent FU. Improved survival with irinotecan and oxaliplatin in pts with metastatic colorectal cancer led to exploration of combination chemotherapy in the adjuvant setting in pts with rectal cancer. Methods: Pts on E3201 (T3–4 Nany M0, T1- 2 N + M0) had the option to receive FU with either pre- or postoperative RT (50.4 Gy). Pts were randomized to postoperative chemotherapy: FU (500mg/m2) + LV (500mg/m2) weekly x 6/8 wks x 3 cycles or irinotecan (FOLFIRI) (180mg/m2) vs oxaliplatin (FOLFOX) (85mg/m2) both administered with LV (400 mg/m2) FU (400mg/m2 bolus) + continuous FU (2.4 gm/m2/46 hours) q 2 wks x 8 cycles. Results: 225 pts of 3150 planned were recruited. 178 pts were randomized and 126 pts submitted treatment completion forms (accrual period 10/03–4/05). The Data Monitoring Committee closed E3201 when the GI Intergroup developed an alternative trial with bevacizumab (E5204). Toxicity information is reported for 93% of pts (165/178) ( Table ). There were no significant differences in toxicity between those pts treated with pre- vs postoperative RT/FU, although, for the subset of pts who received adjuvant FOLFIRI after postoperative RT/FU, there was a trend towards more diarrhea. Conclusion: FOLFOX as rectal adjuvant therapy is a common platform for new clinical trials, although there have been limited toxicity data reported. E3201 provides important comparative toxicity information demonstrating that FOLFOX can be safely administered to rectal cancer pts following chemoradiation. [Table: see text] [Table: see text]