Clinical tolerability and pharmacokinetics of troxacitabine / 中华肿瘤杂志

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).

Phase Ⅰ clinical study of concurrent chemoradiation with hydroxycamptothecin for unresectable or locally relapsed rectal cancer / 中华放射肿瘤学杂志

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.