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

Posted on:2009-09-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:J JinFull Text:PDF
GTID:1114360272481811Subject:Oncology
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Purpose:A phaseⅠstudy 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%,stageⅡ/Ⅲrectal 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 1st to 14th day with a 7-days rest for 2 cycles. PhaseⅠstudy of oxaliplatin in combination with capecitabine and radiotherapy as postoperative treatment for stageⅡandⅢrectal cancerPurpose:A phaseⅠstudy 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 stageⅡorⅢrectal 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 stageⅡandⅢrectal cancerPurpose:To compare the acute toxicity in two prospective,non-randomized trials of adjuvant chemoradiotherapy of capecitabine with or without oxaliplatin in patients with stageⅡandⅢrectal cancer.Materials & MethodsTo further observe the tolerance and toxicity based on two fulfilled phaseⅠstudies,two phaseⅡtrials 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 2nd 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 stageⅡandⅢrectal 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.
Keywords/Search Tags:concurrent radiotherapy, capecitabine, rectal neoplasms, Oxaliplatin, Capecitabine, Concurrent chemoradiotherapy, Rectal cancer, Adjuvant treatment, PhaseⅡ
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