Phase â…  Clinical Tolerance Trial Of Paclitaxtide

Objective:The main purpose to assess the safety,the maximum tolerated dose(MTD) and dose-limiting toxicity(DLT) of intravenously injected Paclitaxtide in advanced cancer patient.The secondary purpose is to observe efficacy of Paclitaxtide.Methods:The eligible subjects with advanced cancers were intravenously injected over 90 minuts with a single-dose of Paclitaxtide without premedication.The starting dose was 60mg/m2 and doses were escalated by a modified Fibonacci series.A cohort of three patients was treated at each dose level and the dose escalation to the next level was continued until DLT reached.The trial finished when one dose level got two patients with DLT.Safety and efficacy were evaluated in 21 days after the injection.Results:A total of 33 patients were enrolled at dose levels ranging from 60 to 420mg/m2 (10 dose levels:60â†'120â†'180â†'240â†'270â†'300â†'330â†'360â†'390â†'420mg/m2). 20 of 33patients were female,13 were male,and the median age wsa 48 years(from 25 to 64 years).Of 33 pts were 9 pts in non-small cell lung cancer,9 pts in breast cancer,4pts in malignant melanoma,2pts in esophageal carcinoma,2pts in colorectal cancer,and other patients developed adrenocortical carcinoma,squamous carcinoma in oral pharynx,primary hepatic carcinoma,small cell lung cancer,metastasis adenocarcinoma in chest wall,ovarian cancer,and small cell cancer in crissum respectively.The major toxicity was myelosuppression and grade 4 neutropenia was the dose limiting toxicity of Paclitaxtide.Other toxicities included nausea,vomiting, fatigue,anorexy,and abnormal ALT/AST.The grade 1 neuropathies were seen at the high dose level.There was no hypersensitiveness without premedication.With dose level increasing,the frequency and degree of myelosuppression were up.A patient with breast cancer(420 mg/m2) had partial response and 17 pts had stable disease.Conclusions:The maximum tolerated dose of Paclitaxtide is 390 mg/m2 and dose-limiting toxicity is grade 4 neutropenia.The recommended regimen is 360 mg/m2 day1 every 3 weeks in Phaseâ…¡clinical trial.