Efficacy of pre-operative chemotherapy and sequential radiation therapy in irresectable rectal carcinoma

ABSTRACT

To evaluate the toxicity and relative response rates of addition of cisplatin to 5-fluorouracil and leucovorin preoperative induction chemotherapy followed by local radiotherapy in irresectable rectal cancer and their impact on radical resectability and sphincter preservation. Between January 2002 and April 2006, 29 patients with locally advanced unresectable rectal cancer received two cycles of 5-fluorouracil 600mg/m[2], I.V 6h infusion D[1]-D[5] and D[22]-D[26], Leucovorin 20mg/m[2], I.V 1h infusion D[1]-D[5] and D[22]-D[26] and cisplatin [CDDP] 60mg/m[2], I.V 6h infusion D[1] and D[22] after good hydration. Radiation treatment was administered after two weeks of the second cycle of chemotherapy. The dose was 45 Gray in 25 fractions over 5 weeks prescribed at isocenter of the plan to include the rectum and the draining lymph node chains. Tumor dimensions were assessed by CT scan before the start and 4 weeks after chemoradiotherapy. Tumor response classification was based on the standard World Health Organization criteria. Complete response [CR] is complete disappearance of the disease. Partial response [PR] is a decrease of 50% of the sum of the products of the greatest perpendicular diameters [SPD]. Progressive disease [PD] is appearance of a new lesion or an increase of 25% in SPD. Stable disease [SD] is no change in SPD or a change not reaching PR or PD. Overall response rate [ORR] is CR plus PR. Our regimen was well tolerated. The main toxicity to it was grade II hematological and grade II and III GIT toxicities in 31% and 65.5% respectively. PR occurred in 58.6% [17/29], SD in 20.7% [6/29] and PD in 20.7% [6/26]. Anterior resection of the rectum with total mesorectal excision and sphincter preservation was done in 37.9% [11/29], abdomino-perineal resection in 31.05% [9/29] and palliative colostomy in 31.05% [9/29]. Radical resectability was achieved in 62.1% [18/29] and cytoreductive surgery in 6.9% [2/29]. After 2 years follow up of resected cases, the 2 years disease free survival was 60% [12/20] with 25% [5/20] local recurrence rate and 15% [3/20] distant metastases to the liver. Our pre-operative combined modality therapy seems to have potential advantage in tumor response, local control and sphincter preservation with tolerable acute and chronic toxicity. Sequential use of chemo-radiotherapy needs more studies to estimate the maximum tolerable dose of chemotherapy and radiotherapy with least side effects