ER toxicity T were fatigue, nausea, vomiting and diarrhea, which were generally mild. Sensory neuropathy in long-term medication was dose limiting. Several Phase Flavopiridol II studies have t-t activity In patients with breast cancer, glioma and acute myelomonocytic leukemia Mie In AML showed mie Cloughesy Johnston et al Gotlib et al tipifarnib also studied in two phase III studies in patients with pancreatic cancer and cancer of the c Lon Van Custem Rao et al, but not proven to be effective. Currently, the combination of tipifarnib with several classes of anti-cancer drug has been studied.
Pr combination with gemcitabine synergy showed clinical tipifarnib Janssen Research Foundation, w W While cisplatin was additive Afatinib Good et al t Skrzat activity t Gemcitabine and cisplatin has been demonstrated in a number of cancers confinement Lich crino et al NSCLC Abratt head and neck HN et al urothelium Hitt et al Kaufman et al Maase van der et al, Geb and Burnett et al rmutterhalskrebs basis of clinical data and pr different mechanisms of gemcitabine Antitumoraktivit tt, cisplatin and tipifarnib phase I trial, this combination was performed. Since the compounds, but potentially important, overlapping toxicity t profiles Myelosuppression t tipifarnib administration was relatively short Hlt days Weight. The main objectives were: i, determine the maximum tolerated dose MTD to the toxicity of t II and III DLT t doselimiting to investigate the pharmacokinetics of each agent, tipifarnib I particularly affect the pharmacokinetics of gemcitabine and cisplatin to characterize happy.
Patients and methods were f Rderf compatibility available when rderf F ONE beneficiaries HIGEN best histological or cytological had advanced solid tumors for which there is no cure. Other parameters included a WHO performance status and X years. Radiotherapy or chemotherapy for several weeks notice before they are interrupted in the study, X or weeks nitrosoureas or mitomycin C. All patients had an acceptable function as bone marrow neutrophil count ANC X ml ttchen platelets ml mmol Hb X and X and adequate hepatic and renal function Creatinine clearance ml min X defined, total bilirubin is defined p. Upper limit of normal and AST and ALT p. times the upper limit of normal, or p-times the upper limit of normal, in the case of liver metastases. The study protocol was reported h medical ethics committee of the capital and all patients their written consent.
Tipifarnib treatment plan and design of the study by Johnson & Johnson Pharmaceutical Research & Development mg Set is. Gemcitabine and cisplatin were the drugstore chain h if the capital increase Beh and compliance requests Rdlichen. T twice tipifarnib administered orally, at a distance of a few hours. Tipifarnib a day every day of the cycle was given. Iv infusion of gemcitabine and cisplatin was as t min and was given intravenously Se days infusion administered ah, Ant comments min after the administration of gemcitabine. T for nephrotoxicity T been implemented to minimize Fl Che and a day after the hydration schedule. Pre-and post-hydration was ml