洛铂联合５-ＦＵ／ＣＦ治疗晚期胃、结直肠癌的剂量爬坡试验

目的　观察国人对不同剂量洛铂联合５-ＦＵ／ＣＦ治疗晚期胃、结直肠癌的耐受性、毒性反应以及与剂量的关系，探讨洛铂在联合化疗中的人体安全耐受剂量。方法　选取洛铂从低剂量逐渐至高剂量，５-ＦＵ和ＣＦ剂量不变，每剂量组至少３例受试者。初始剂量为洛铂２５ｍｇ／ｍ^２ｄ_１，５-ＦＵ４００ｍｇ／ｍ^２ｄ_１～ｄ_５，ＣＦ２００ｍｇ／ｍ^２ｄ_１～ｄ_５，２１ｄ为１周期；如无明显毒性反应则进入下一剂量组，直至最大耐受量（ＭＴＤ）或５０ｍｇ／ｍ^２。结果　１８例晚期胃、结直肠癌患者进入试验，分别进行了６个剂量组的研究，最高剂量组为５０ｍｇ／ｍ２，未观察到ＭＴＤ。主要毒性反应为血红蛋白减少、白细胞减少，其次为恶心、呕吐和腹泻，所有患者未出现３～４级不良反应。结论　洛铂联合５-ＦＵ／ＣＦ毒性反应较轻，患者耐受性较好。推荐使用洛铂４５ｍｇ／ｍ^２联合５-ＦＵ４００ｍｇ／ｍ^２和ＣＦ２００ｍｇ／ｍ^２用于进一步临床研究。

Dose climbing trial of lobaplatin combined with 5-FU/CF in patients with advanced gastric or colorectal cancer

Objective To evaluate the tolerability and toxic reaction of the combination of fluorouracil,leucovorin and different dose lobaplatin for patients with advanced gastric or colorectal cancer and investigate the safe dose of lobaplatin in the combined chemotherapy.Methods From low dose group to high dose group,each one had 3 patients at least.Primary group received 25mg/m2of lobaplatin which was administrated at d1 of chemotherapy.The dose of lobaplatin would increase gradually until MTD or 50mg/m2.Results Eighteen patients were enrolled in the clinical research that included 6 groups.The highest dose of loba platin was 50mg/m2,and we did not obtain MTD.The major toxicities were anemia and neutropenia,other related toxicities included nausea,vomiting and diarrhea.No grade Ⅲ-Ⅳ toxicity was observed.Conclusion The combination of lobaplatin,leucovorin and fluorouracil shows a favorable toxicity profile in patients with advanced gastric or colorectal cancer.The combination regimen of 45mg/m2 lobaplatin,leucovorin and fluorouracil was recommended in further clinical study.