Phase II Study of Neoadjuvant FOLFOX4 Followed by Combined Chemoradiotherapy in Locally Advanced Rectal Mucinous Adenocarcinoma

  • Elsaid A.A.
  • Saad A.
  • Awad N. M.


Introduction: Rectal mucinous 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 + chemoradiation 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 Mayoclinic
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 chemoradiotherapy
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. Anastomotic 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
chemoradiotherapy 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 chemoradiation in a randomized study.

Key words: Neoadjuvant , FolFox4, Rectal Adenocarcinoma, Mucinous

Author Biographies

Elsaid A.A.
Department of Clinical Oncology , Faculty of Medicine, University of Alexandria.
Saad A.
Department of General Surgery, Medical Research Institute, University of Alexandria.
Awad N. M.
Department of Epidemiology, High Institute of Public Health, University of Alexandria.