Induction chemotherapy [ICT] followed by preoperative chemo radiotherapy and total mesorectal excision surgery for locally advanced rectal cancer

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[2] D1 and D15] + FA [200 mg/m[2] 2 hours infusion D1, 2 and D15, 16] followed by 5-FU bolus [400 mg/m[2] D1, 2 and D15, 16] + 5-FU continuous infusion [1200 mg/m[2] 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 [104] 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

Concomitant chemotherapy and radiotherary in locally advanced cervical cancer

Radiotherapy has been the standard therapy for locally advanced cervical cancer for decades. Neoadjuvant chemotherapy had failed to improve survival in these patients. Concomitant combination of chemotherapy and radiotherapy is promising in improving survival in many clinical trials with risk of increasing radiation reactions. We report a study comparing the combination of weekly cisplatin concomitant with irradiation versus irradiation alone in the same dose and technique. Sixty patients with cervical cancer [stage JIB-I VA] were randomized into two arms; either weekly cisplatin 40 mg/m2 plus radiotherapy [group A] or radiotherapy 45 Gy whole pelvis followed by intracavitary irradiation [to raise the dose to point A to 80 Gy] then parametrial irradiation with central shield for another 15 Gy [group B]. There was a significant difference in response to treatment in both arms [90% Vs. 69% respectively F<0.05]. Also, there was a statistically superior progression free and overall survival in the concomitant group [P<0.043 and p<0.0336]. The toxicity reported was generally limited in both groups and of lower grade despite being significantly higher in patients who received combination treatment. We conclude that combined modality is feasible and could be well tolerated in our patients population