ABSTRACT
PURPOSE: Gemcitabine (2',2'-difluorodeoxycytidine) is an antineoplastic agent with activity against a variety of solid tumors. To investigate its in vitro activity toward cervical cancer, we exposed six cervical cancer cell lines to gemcitabine. METHODS: Combinational cytotoxic studies using viability tests and clonogenicity assays. RESULTS: Gemcitabine was cytostatic and cytotoxic in some of the lines at peak plasma concentrations similar to those achieved in clinical trials. Gemcitabine was also found to effectively synergize with cisplatin and showed a radiosensitizing effect in these cells. The cytotoxicity observed in sensitive cell lines was due to apoptosis, as demonstrated by DNA fragmentation assays. CONCLUSIONS: We recommend performing additional in vitro experimentation so that these results can be confirmed to support clinical trials of gemcitabine in cervical cancer patients both as first-line therapy and with concomitant radiation.
Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Radiation-Sensitizing Agents/pharmacology , Uterine Cervical Neoplasms/pathology , Apoptosis , Cell Survival , Cisplatin/pharmacology , DNA Damage , Drug Interactions , Female , HeLa Cells , Humans , Tumor Cells, Cultured , GemcitabineABSTRACT
Using a probabilistic model with parameters from four radiotherapy protocols used in Mexican hospitals for the treatment of cervical cancer, we have calculated the distribution of dose to cells in peripheral blood of patients. Values of the mean dose to the lymphocytes during and after a 60Co treatment are compared to estimates from an in vivo chromosome aberration study performed on five patients. Calculations indicate that the mean dose to the circulating blood is about 2% of the tumor dose, while the mean dose to recirculating lymphocytes may reach up to 7% of the tumor dose. Differences up to a factor of two in the dose to the blood are predicted for different protocols delivering equal tumor doses. The data suggest mean doses higher than the predictions of the model.