Phase Ⅰ study of dose escalation of oxaliplatin added to capecitabine during intensity-modulated radiation therapy patients with locally advanced rectal cancer / 中华放射医学与防护杂志

ABSTRACT

Objective To discuss the maximum tolerated dose of oxaliplatin based on 5-fluorouracil derivative in patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy.Methods From Mar 2015 to Oct 2015,15 locally advanced rectal cancer patients (T3,T4/N +) who received intensity modulated radiotherapy and concurrent chemotherapy with capecitabine and oxaliplatin were enrolled in this study.The prescription dose was 50.6 Gy for gross tumor volume(GTV) and 41.8 Gy for clinical tumor volume(CTV) in 22 fractions within 30 d with concomitant boost.There were four dose-level groups of oxaliplatin as 100,110,120 and 130 mg/m2 tri-weekly and fixed capecitabine dose (825 mg/m2 bid d1-5 per week).The first 12 patients were randomly assigned into 4 groups.For the 130 mg/m3 group,another 3 patients were enrolled because of dose-limiting toxicity (DLT).Treatment related toxicities and response rates were evaluated.Results The most common adverse events(AE) were radiation enteritis,skin reactions,nausea,fatigue,urinary system AE and bone marrow suppression.There was a trend of increase by the dose level of oxaliplatin for toxicities.Groups 100,110 and 120 mg/m2 had none DLT,while group 130 mg/m2 had 1 patient for grade 3 thrombopenia and 1 patient for grade 3 nausea.Postoperative pathology showed that all patients achieved tumor downstaging,among which 0,1,2,3 cases achieved complete remission of the four groups,respectively.Conclusions The combination regimen of capecitabine and oxaliplatin is safe and effective according to the preliminary results.The maximum tolerated dose of oxaliplatin was 130 mg/m2 tri-weekly.