Phase II study of neoadjuvant folfox4 followed by combined chemoradiotherapy in locally advanced rectal mucinous adenocarcinoma

Abstract EN

Introduction: Rectal mutinous adenocarcinoma (RMAD) often present at an advanced stage and have the poorest overall prognosis.

Methods : This is a single arm phase II toxicity/efficacy study of neoadjuvant FOLFOX4 + chemo radiation in ptns with locally advanced RMAD.

Between 10 / 99 and 8 / 05, 52 ptns aged 18 to 65 years, with locally advanced RMAD (12 T3 and 40 T4) were assessed retrospectively.

Staging workup was done by endoscopic ultrasound and CT scan.

All patients received 2 months of FOLFOX4.

The cycles were repeated every 2 weeks for a total of 8 weeks.

Starting on wk 9, 5 FU / lv was given as in Mayo clinic regimen with concomitant radiotherapy at 45Gy in 25 fractions followed by 9 Gy boost to tumor bed.

TME was planned at 4-6 wks from completion of FOLFOX4.

2 more cycles of FOLFOX4 were given postoperatively.

Results: All patients (52) undergoing neoadjuvant chemo radiotherapy completed therapy as planned, with no treatment-related interruptions.

No grades 3 or 4 toxicities were observed.

Overall objective response rates by RECIST criteria were 89% at the completion of neoadjuvant therapy.

40 / 52 ptns experienced improvement in diarrhea / constipation (90.4%), obstructive symptoms (20 / 25 ptns) and weight loss in 100% of ptns during assessment on day 24 from start of FOLFOX4.

Additionally all ptns experienced improvement in rectal bleeding and pelvic pain as shown in a verbal questionnaire.

8 of 10 patients deemed irresectable prior to the treatment underwent total mesorectal excision (TME) with negative radial margins.

Anastigmatic leakage occurred in 4 ptns.

Wound infection occurred in 2 patients.

Delayed complications in the form of stomal stricture occurred in 2 patients (1 requiring surgical revision).

All eight patients underwent resection with negative margins.

Pathological CR was found in 12 ptns and in an additional 20 ptns, only microscopic tumor foci were found on surgical specimens.

At a median follow-up of 24 months, 2 ptns experienced locoregional relapse.

Conclusion: neoadjuvant FOLFOX4 followed by combined chemo radiotherapy in RMAD results in marked tumor regression, rapid symptomatic improvement and the attainment of R0 resection.

Given the low toxicity and promising activity, this regimen is being compared to standard synchronous 5FU- pelvic chemo radiation in a randomized study.