Current evidence suggests that preoperative chemoradiotherapy [CRT] provides optimal locoregional control for patients [pts] with T3, T4 rectal carcinoma, However, distant failure remains common.
Induction chemotherapy [ICT], when administered at full systemic dose before CRT, is more likely to address the current major hurdle of controlling distant metastasis in rectal cancer. The role of ICT before CRT in improving disease-free or overall survival has yet to be established. To assess the role of using neoadjuvant Cisplatin, 5-fluorouracil [5-FU] and folinic acid [FA] as an ICT which is followed by preoperative CRT and total mesorectal excision [TME] surgery in the management of newly diagnosed patients with T3, 4 rectal cancer. Between October 1999 and August 2004, 104 patients with proved adenocarcinoma of the rectum were assessed retrospectively. Their ages ranged between 18 and 65 years old Twenty four pts were T3 and 80 pts were T4 rectal carcinoma. Their performance status ranged between zero and one [PS 0-1]. Patients received 2 cycles of ICT over 2 months. Each cycle comprised: Cisplatin [40mg/m  D1 and D15] + FA [200 mg/m  2 hours infusion D1, 2 and D15, 16] followed by 5-FU bolus [400 mg/m  D1, 2 and D15, 16] + 5-FU continuous infusion [1200 mg/m  D1, 2 and D15, 16]. This cycle was repeated every 28 days starting from day 1. Starting on week 9, the 5-FU and FA were given following the regimen of the Mayo-clinic [D1-5, D21-25] with concomitant radiotherapy 45Gy in 25 fractions followed by 9 Gy boost to the primary tumor. TME was planned at 4-6 weeks from completion of CRT. Two more cycles of FOLFC [Cisplatin, 5-FU and FA] were given post-operatively. All patients  undergoing preoperative ICT followed by CRT completed therapy as planned, with no treatment-related interruptions. No grade III or IV toxicity was encountered. The radiological response rate [RR] after ICT was 75% and 4 weeks after CRT was 89.4%. Twenty patients had complete radiological response and 73 patients had only partial response. Totally, 92% of the patients had subjective remission of their tumor related symptoms in a median of 24 days from start of ICT.90.4% and 80% of the pts with diarrhea/constipation, and with obstructive symptoms were improved consecutively. Weight gain was achieved in 100% of pts. Reduction in rectal bleeding and pelvic pain occurred in 100% of pts.17 of 20 patients who were considered prior to the treatment to have border line resectable tumor underwent TME with negative radial margins only 93 patients were operated and all underwent curative resection [R0] with clear histological circumferential resection margin [CRM]. Pathological CR [pCR] was found in 32 patients and in an additional 41 patients only microscopic tumor foci were found on surgical specimens. Anastomotic leakage occurred in 8 patients [7.7%]. Wound infection occurred in 4 patients [3.8%]. Delayed complications occurred in 3 patients [3.13%] ; one required surgery for a stomal stricture after abdomino perineal resection. After a median follow-up of 16 months, two patients [2.15%] had developed recurrence. ICT followed by synchronous CRT and TME results in marked tumor regression, rapid symptomatic response and achievement of RO resection with minimal toxicity and promising activity. The majority of patients considered inoperable prior to receiving this treatment underwent successful excision. Further follow-up would be required to see whether reduction of distant metastasis and thereby, improvement of overall survival can be achieved with this approach
Y. Elkerm ,M. El Riwini ,S. Al Batran ,E. Jager ,A. Elsaid ,
Induction chemotherapy [ICT]followed by preoperative chemo radiotherapy and total mesorectal excision surgery for locally advanced rectal cancer,
Bull. Alex. Fac. Med. 2006;
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