Ii - Iii Of Resectable Rectal Cancer Synchronous Chemoradiotherapy I / Ii Clinical Study

Purpose:A phaseâ… study was conducted to determine the maximal tolerated dose and the dose-limiting toxicity of capecitabine with standard RT as adjuvant treatment in patients with rectal cancer.Methods and Materials:Patients aged 18～75 years old,Karnofsky scored≥70%,stageâ…¡/â…¢rectal cancer after curative surgery were eligible.Total RT dose was delivered as DT 50 Gy in the fraction of 2.0 Gy per day for 5 weeks to the pelvic area.Capecitabine was administered concurrently with radiotherapy in escalating doses,twice daily with 12 hour interval,consisting of 2 cycles of 14 days separated by a seven day rest.Dose-limiting toxicity (DLT) included grade 3 or grade 4 hematologic and nonhematologic toxicity.Results:From Mar 2004 to May 2005,24 patients were enrolled at the following dose levels:daily 1000 mg/m²(3 patients),1200 mg/m²(3 patients), 1400 mg/m²(3 patients),1500 mg/m²(3 patients),1600 mg/m²(6 patients), and 1700 mg/m²(6 patients).Dose-limiting toxicity was observed in 1 patient at 1600 mg/m²(grade 3 diarrhea),and in 2 patients at 1700 mg/m²(1 patient had grade 3 and 1 grade 4 diarrhea).Conclusion:Diarrhea is the most common side effect.The maximal tolerated dose(MTD) of capecitabine given concurrently with RT was daily 1600 mg/m², daily from 1^st to 14^th day with a 7-days rest for 2 cycles. Phaseâ… study of oxaliplatin in combination with capecitabine and radiotherapy as postoperative treatment for stageâ…¡andâ…¢rectal cancerPurpose:A phaseâ… study was conducted to determine the maximal tolerated dose(MTD) and the dose-limiting toxicity(DLT) of oxaliplatin(OXA) combined with capecitabine(CAP) and radiotherapy(RT) as adjuvant treatment in patients with operable rectal cancer.Methods & Patients:A total of 21 patients with stageâ…¡orâ…¢rectal adenocarcinoma after curative surgery were treated with RT to total dose of 50Gy in 5 weeks.Oxaliplatin was administered at a dosage of 40(n=6),50(n=3),60(n=3),70(n=3) or 80 mg/m² (n=6) once a week for 2 weeks(1st cycle) followed by a 2nd cycle after 7-day break.Capecitabine at a fixed dose of 1300 mg/m²/d was administered orally with same schedule of OXA.DLT was defined as grade 3 or 4 hematological and non-hematological toxicity.Results:Grade 1-3 leukopenia,diarrhea and nausea/vomiting were the most common toxic side effects,and most were grade 1-2.The dose-limiting toxicity was first observed in 1 of 3 patients at 40 mg/m²(grade 3 diarrhea) and in none of the following 3 patients at the same level,nor in patients who received dose levels of 50-70 mg/m².At 80 mg/m²,DLT occurred in 3 of 6 patients(1 grade 4 leukopenia,and 2 grade 3 diarrhea).Conclusion:Oxaliplatin combined with a fixed dose of CAP 625mg/m² twice a day by mouth plus RT in adjuvant setting were tolerable and clinically feasible.The MTD of OXA in this setting was 70 mg/m²,comparable to the MTD of OXA at the neoadjuvant setting. Preliminary evaluation of acute side effects in two concurrent chemoradiotherapy of capecitabine with or without oxaliplatin in patients with stageâ…¡andâ…¢rectal cancerPurpose:To compare the acute toxicity in two prospective,non-randomized trials of adjuvant chemoradiotherapy of capecitabine with or without oxaliplatin in patients with stageâ…¡andâ…¢rectal cancer.Materials & MethodsTo further observe the tolerance and toxicity based on two fulfilled phaseâ… studies,two phaseâ…¡trials were launched respectively,from March 2005 to November 2007.118 patients were treated with concurrent capecitabine and radiotherapy(Cap-CRT trial),with radiotherapy given to the peCFic of DT 50Gy/25F/5wks,and capecitabine at a dosage of 1600 mg/m²,daily in twice, for 2 weeks followed by a 2^nd cycle after a rest of 7 days.In another trial, oxaliplatin and capecitabine plus radiotherapy(Cap-Oxa-CRT trial,n=90) was performed with a same schedule of radiotherapy and chemotherapy,while oxaliplatin at a dosage of 70 mg/m² once a week,and capecitabine of 1300 mg/m²/d,both for 2 cycles.ResultsGrade 1-4 leukopenia,diarrhea and nausea were the most common toxic side-effects among the patients in both trials,accounting for 70.2%(146/208), 65.9%(137/208) and 42.3%(88/208).However,some patients experienced grade 3 or 4 side effects,including diarrhea(24.0%;1%),leukopenia(4.3%; 0.0%),radiation-induced dermatitis(3.8%;0.0%),cramping abdominal pain (1.0%;0.0%) and fatigue(0.5%;0.0%).When comparing the incidence of grade 1-4 side-effects between the two trials,patients in Cap-Oxa-CRT trial experienced significantly more non-hemotological side-effects,mainly in GI, including nausea(68.9%vs.22.0%,p=0.000),diarrhea(76.7%vs.57.6%, p=0.009),fatigue(47.8%vs.23.7%,p=0.000),hand-foot syndrome(14.4%vs. 4.2%,p=0.029) and lost of appetite(50.0%vs.27.9%,p=0.000),but no significant difference between hematological side-effects,i.e,leukopenia, anemia or thrombocytopenia.If further comparing the incidence of grade 3 and 4 toxicity,the only significant difference was more grade 3 and 4 diarrhea in Cap-oxa-CRT trial(33.3%vs.18.6%,p=0.009).Although the higher incidence of side-effects in Cap-Oxa-CRT trial,no matter total grade 1-4 or only grade 3 and 4,there was no significant difference in a need to interrupt either radiotherapy(10.2%vs.6.7%,p=0.46) or chemotherapy(9.3%vs.19.1%, p=0.09) in Cap-CRT or Cap-oxa-CRT trial.ConclusionIn patients with stageâ…¡andâ…¢rectal adenocarcinoma treated with adjuvant chemoradiotherapy,both concurrent chemotherapy regimens are tolerable.No significant difference for treatment interruption or delay,though patients treated with oxaliplatin,capecitabine and radiotherapy have suffered from more grade 3 and 4 diarrhea.The long-term survival and local control of the two trials is being expected.