Enhancement of radiation effects by combined docetaxel and carboplatin treatment in vitro.
This study was designed to evaluate the combination of docetaxel (Taxotere) and carboplatin for radiopotentiation in vitro. H460 human lung carcinoma cells were treated with docetaxel (or paclitaxel) for 1 h and rinsed. After 24 h, the cells were treated with carboplatin for 1 h, irradiated, and colony forming ability was assesed. Using various doses of docetaxel with 100 microM carboplatin, the dose enhancement ratio (D.E.R.) for drugs only was 1.26. When 25 nM docetaxel was used with various doses of radiation, the radiation D.E.R. was 1.41. With all three agents combined, and after normalization for combined drug effects, the radiation D.E.R. was 1.55. Similar values were obtained using paclitaxel with these agents. Significant redistribution of cells into the radiosensitive G2/M phase was observed using a dose of paclitaxel (750 nM), which also caused radiation enhancement. However, an equally cytotoxic dose of docetaxel (25 nM) did not result in any cell cycle redistribution; this phenomenon was only observed at higher doses. This study shows that the combination of docetaxel and carboplatin enhance the effects of radiation in vitro more effectively than either drug seperately. In addition, our data show that the mechanism of radiopotentiation by docetaxel probably does not involve a G2/M block in H460 cells.
Amorino
G P
GP
Vanderbilt University Medical Center, Department of Radiation Oncology, Nashville, Tennessee, USA. george.amorino@mcmail.vanderbilt.edu
Hamilton
V M
VM
Choy
H
H
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D018714:Radiotherapy, Adjuvant; D043823:Taxoids; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin; D017239:Paclitaxel