RÉSUMÉ
Objective: To investigate the safety and efficacy of troxatabine in advanced or relapsed malignant tumors resistant to standard therapy in China. Methods: This is a phase Ⅰ prospective study. During dose escalation, patients in Cancer Hospital, Chinese Academy of Medical Sciences received a single-dose intravenous infusion of troxacitabine. The planned dosing groups were 1.8, 3.6, 4.8, 6.4 and 8.0 mg/m(2) on days 1 and 8 every 3 weeks. The data of all patients were collected for safety analyses. Safety and tolerability were evaluated by monitoring adverse events. Results: Nineteen patients were enrolled from April 2018 to May 2019. The major adverse events were fatigue (89.5%, 17/19), leukopenia (84.2%, 16/19) and neutropenia (78.9%, 15/19). The dose limiting toxicity was neutropenia. The maximum tolerated dose was 6.4 mg/m(2). The best effect was stable disease (43.8%). The half-life of elimination phase from 15.91 hours to 76.63 hours in each dose group. Conclusions: The toxicity of troxacitabine is well tolerant. We recommend that the dose for Phase Ⅱ clinical trial should be 6.4 mg/m(2).
Sujet(s)
Humains , Antinéoplasiques/effets indésirables , Dose maximale tolérée , Tumeurs/traitement médicamenteux , Neutropénie/induit chimiquement , Études prospectivesRÉSUMÉ
ObjectiveTo determine the maximal tolerated dose and the dose-limiting toxicity of hydroxycamptothecin (HCPT)concurrently combined with three-dimensional conformal radiotherapy (3DCRT) for unresectable or locally relapsed rectal cancer.Methods Twenty-two patients with rectal cancer were enrolled into phase Ⅰstudy between 2004 -2007. HCPT was intravenously administered concurrently with 3DCRT weekly,dose given from 6,8,10 mg/m2 or twice a week,dose given from 4,6,8,10 mg/m2,respectively.Total radiation dose of 50 Gy was delivered to the whole pelvis at a fraction of 2 Gy per day for 5 weeks,with 10 - 16 Gy subsequent boost to tumor area.Dose-limiting toxicities (DLT) were defined as grade 3 or higher non-hematologic toxicity or grade 4 hematologic toxicity.ResultsIn the twice a week group,DLTs of grade 3 diarrhea were observed in 2 patient treated at dose of 6 mg/m2.In the weekly group,DLTs of grade 3 diarrhea and radiation-induced dermatitis were observed in Ⅰ patient at dose of 8mg/m2,and were not observed in the next 3 patients at the same dose level.However,at dose of 10 mg/m2,2 patients had grade 3 diarrhea or nausea.The 5-year overall survival rate was 23% and the median survival time was 18 months.ConclusionsHCPT given concurrently with 3DCRT is safe and tolerable for patients with unresectable or locally relapsed rectal cancer.Either 8 mg/m2 weekly or 4 mg/m2 twice a week can be recommended for further study.The dose-limiting toxicities are grade 3 diarrhea,nausea and radiation-induced dermatitis.