PURPOSE: To investigate the pharmacological effects of different erlotinib (ER) and gemcitabine (GM) combination schedules by in vitro and in vivo experiments and PK/PD models in non-small cell lung cancer cells. METHODS: H1299 cells were exposed to different ER combined with GM schedules. Cell growth inhibition was analyzed to evaluate these schedules. A preclinical in vivo study was then conducted to compare tumor suppression effects of different schedules in H1299 xenografts. PK/PD models were developed to quantify the anti-tumor interaction of ER and GM. RESULTS: Synergism was observed when ER preceded GM, but other sequences showed antagonism. The optimal in vitro schedule, or interval schedule, was applied to the animal study, which showed greater anti-tumor effect than simultaneous group. PK/PD models implied that interaction of the two drugs was additive in simultaneous treatment but synergistic in interval schedule. The simulation results showed that interval schedule can delay tumor growth for a longer time, and demonstrated more evident anti-tumor effect compared with simultaneous group if the treatment duration was longer. CONCLUSIONS: Interval schedule of the two drugs can achieve synergistic anti-tumor effect, and is superior to simultaneous treatment.
PURPOSE: To investigate the pharmacological effects of different erlotinib (ER) and gemcitabine (GM) combination schedules by in vitro and in vivo experiments and PK/PD models in non-small cell lung cancer cells. METHODS: H1299 cells were exposed to different ER combined with GM schedules. Cell growth inhibition was analyzed to evaluate these schedules. A preclinical in vivo study was then conducted to compare tumor suppression effects of different schedules in H1299 xenografts. PK/PD models were developed to quantify the anti-tumor interaction of ER and GM. RESULTS: Synergism was observed when ER preceded GM, but other sequences showed antagonism. The optimal in vitro schedule, or interval schedule, was applied to the animal study, which showed greater anti-tumor effect than simultaneous group. PK/PD models implied that interaction of the two drugs was additive in simultaneous treatment but synergistic in interval schedule. The simulation results showed that interval schedule can delay tumor growth for a longer time, and demonstrated more evident anti-tumor effect compared with simultaneous group if the treatment duration was longer. CONCLUSIONS: Interval schedule of the two drugs can achieve synergistic anti-tumor effect, and is superior to simultaneous treatment.
Authors: Roy S Herbst; Diane Prager; Robert Hermann; Lou Fehrenbacher; Bruce E Johnson; Alan Sandler; Mark G Kris; Hai T Tran; Pam Klein; Xin Li; David Ramies; David H Johnson; Vincent A Miller Journal: J Clin Oncol Date: 2005-07-25 Impact factor: 44.544
Authors: Ulrich Gatzemeier; Anna Pluzanska; Aleksandra Szczesna; Eckhard Kaukel; Jaromir Roubec; Flavio De Rosa; Janusz Milanowski; Hanna Karnicka-Mlodkowski; Milos Pesek; Piotr Serwatowski; Rodryg Ramlau; Terezie Janaskova; Johan Vansteenkiste; Janos Strausz; Georgy Moiseevich Manikhas; Joachim Von Pawel Journal: J Clin Oncol Date: 2007-04-20 Impact factor: 44.544
Authors: Brian Higgins; Kenneth Kolinsky; Melissa Smith; Gordon Beck; Mohammad Rashed; Violeta Adames; Michael Linn; Eric Wheeldon; Laurent Gand; Herbert Birnboeck; Gerhard Hoffmann Journal: Anticancer Drugs Date: 2004-06 Impact factor: 2.248
Authors: M P Morelli; T Cascone; T Troiani; F De Vita; M Orditura; G Laus; S G Eckhardt; S Pepe; G Tortora; F Ciardiello Journal: Ann Oncol Date: 2005-05 Impact factor: 32.976
Authors: Zhihui Wang; Joseph D Butner; Vittorio Cristini; Thomas S Deisboeck Journal: J Pharmacokinet Pharmacodyn Date: 2015-01-15 Impact factor: 2.745
Authors: Anne Monks; Yingdong Zhao; Curtis Hose; Hossein Hamed; Julia Krushkal; Jianwen Fang; Dmitriy Sonkin; Alida Palmisano; Eric C Polley; Laura K Fogli; Mariam M Konaté; Sarah B Miller; Melanie A Simpson; Andrea Regier Voth; Ming-Chung Li; Erik Harris; Xiaolin Wu; John W Connelly; Annamaria Rapisarda; Beverly A Teicher; Richard Simon; James H Doroshow Journal: Cancer Res Date: 2018-10-24 Impact factor: 12.701