In vitro study on the schedule-dependency of the interaction between pemetrexed, gemcitabine and irradiation in non-small cell lung cancer and head and neck cancer cells.

1 h dFdC --> RT is the most rational design and would, after confirmation in an in vivo setting, possibly provide the greatest benefit in the clinic. -->
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Substance Nomenclature: 0 (Glutamates)
04Q9AIZ7NO (Pemetrexed)
0W860991D6 (Deoxycytidine)
5Z93L87A1R (Guanine)
0 (Gemcitabine)
Entry Date(s): Date Created: 20100821 Date Completed: 20110203 Latest Revision: 20221207
Update Code: 20231215
PubMed Central ID: PMC2931492
DOI: 10.1186/1471-2407-10-441
PMID: 20723210
Autor: Wouters A; Laboratory of Cancer Research and Clinical Oncology, Department of Medical Oncology, University of Antwerp, 2610 Wilrijk, Belgium. an.wouters@ua.ac.be, Pauwels B, Lardon F, Pattyn GG, Lambrechts HA, Baay M, Meijnders P, Vermorken JB
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2010 Aug 19; Vol. 10, pp. 441. Date of Electronic Publication: 2010 Aug 19.
DOI: 10.1186/1471-2407-10-441
Abstrakt: Background: Based on their different mechanisms of action, non-overlapping side effects and radiosensitising potential, combining the antimetabolites pemetrexed (multitargeted antifolate, MTA) and gemcitabine (2',2'-difluorodeoxycytidine, dFdC) with irradiation (RT) seems promising. This in vitro study, for the first time, presents the triple combination of MTA, dFdC and irradiation using various treatment schedules.
Methods: The cytotoxicity, radiosensitising potential and cell cycle effect of MTA were investigated in A549 (NSCLC) and CAL-27 (SCCHN) cells. Using simultaneous or sequential exposure schedules, the cytotoxicity and radiosensitising effect of 24 h MTA combined with 1 h or 24 h dFdC were analysed.
Results: Including a time interval between MTA exposure and irradiation seemed favourable to MTA immediately preceding or following radiotherapy. MTA induced a significant S phase accumulation that persisted for more than 8 h after drug removal. Among different MTA/dFdC combinations tested, the highest synergistic interaction was produced by 24 h MTA followed by 1 h dFdC. Combined with irradiation, this schedule showed a clear radiosensitising effect.
Conclusions: Results from our in vitro model suggest that the sequence 24 h MTA --> 1 h dFdC --> RT is the most rational design and would, after confirmation in an in vivo setting, possibly provide the greatest benefit in the clinic.
Databáze: MEDLINE
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