The combined effect of fludarabine monophosphate and radiation as well as gemcitabine and radiation on squamous carcinoma tumor cell lines in vitro.
OBJECTIVE
Despite proven antitumor activity of gemcitabine in chemoradiotherapy of advanced head and neck cancer, many authors refer to severe acute and late local and haematological toxicity. Fludarabine does imply nearly the same mechanisms of action as gemcitabine, inhibiting various enzymes involved in DNA replication. This investigation focuses on the combined effect of either fludarabine or gemcitabine and radiation on human squamous carcinoma cell lines in vitro, providing data for future decisions on head and neck chemoradiotherapy regimen.


METHODS
ZMK-1, A549, BW-225, GR-145, OH-65 and CaSki cell lines were incubated with either drug at defined schedules and irradiated at a single fraction dose of 2 Gy every 24 hours up to 8 Gy. Cytotoxic effects were measured by colony-forming assays, quantitative determination of apoptosis and isobologram analysis.


RESULTS
Incubation of fludarabine led to a radiosensitizing effect in the A549, CaSki and ZMK-1 cell lines and an additive effect in the BW-225, GR-145 and OH-65 cell lines. Treatment with gemcitabine only indicated significant radiosensitization in the CaSki cell line in combination with augmented resistance against gemcitabine application alone.


CONCLUSIONS
Our results reveal a potential radiosensitizing effect of fludarabine and its possible application in chemoradiotherapy of advanced head and neck carcinoma and possibly other tumor entities.
Nitsche
Mirko
M
Department of Radiation Oncology, Georg-August-Universitat Gottingen, Gottingen.
Christiansen
Hans
H
Hermann
Robert M
RM
Lucke
Eva-Maria
EM
Peters
Kerstin
K
Rave-Frank
Margret
M
Schmidberger
H
H
Pradier
Olivier
O
D017209:Apoptosis / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D001084:Vidarabine Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000093542:Gemcitabine
D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D001084:Vidarabine Phosphate; C042382:fludarabine phosphate; D000093542:Gemcitabine