Safety and tolerability of raltitrexed in patients with locally advanced recurrent and metastatic colorectal cancer:a phase Ⅳ trial

QIN Shukui; YANG Liuqing; LI Jin; LIU Yunpeng; CHENG Ying; XU Nong; YE Zhengbao; XU Jianming; BAI Yuxian; LIANG Jun; HUANG Jianjin; ZHENG Leizhen; YU Ding; WANG Zhehai

doi:10.3969/j.issn.1009-0460.2017.03.002

Abstract：Objective To evaluate the post-marketing safety and efficacy of homemade raltitrexed monotherapy(Saiweijian) in patients with locally advanced or recurrent and metastatic colorectal cancer.Methods The perspective,single-arm,open-label,nationalwide multi-center,phaseⅣtrial was conducted.Patients with locally advanced or recurrent and metastatic colorectal cancer received raltitrexed(3 mg/m2) as a 15 min infusion on day 1,every 21 days.Treatment was conducted until disease progression or unaccepted toxicity.The primary objective was safety according to NCI CTC 3.0 criteria and the secondary objectives were disease control rate(DCR),progression free survival(PFS) and overall survival(OS).The objective response was evaluated according to RECIST 1.1 criteria.Results Of the total 215 patients enrolled,205 patients were evaluable for safety assessments and 204 patients were included in the full analysis set(FAS).Totally 92 patients had 394 adverse events(AEs) during the study.A majority(94.4%) of AEs was grade 1-2 and only 5.3% was grade 3-4.The serious adverse events(SAE) were reported by 5.8% of patients.The most common AEs were the increase of transaminase,leukopenia,nausea and pain.By continuous monitoring of liver enzyme during the treatment,the alanine transaminase(ALT) and aspartate transaminase(AST) levels began to rise after the first course of raltitrexed,peaked in the second or third cycle and decline with continued dosing.But alkaline phosphatase(ALP) and bilirubin did not elevated at the same time,leukopenia and neutropenia were observed in 13.7% of patients.In digestive systems,the most common AEs were nausea(8.3%),diarrhea(4.4%) and vomiting(3.9%).The electrocardiographic abnormality was rare.No treatment-related deaths occurred.DCR was 49.5% for second-line treatment and 37.3% for third-line treatment.The median OS was 13.6 months and 8.9 months respectively.Conclusion Homemade raltitrexed monotherapy(Saiweijian) is safe with manageable AEs and well effective in terms of both DCR and OS in patients with locally advanced or recurrent and metastatic colorectal cancer.There is no complete cross drug resistance between raltitrexed and 5-FU.It is worth to be widely applied in clinical practice further.