PACLITAXEL - A RADIATION SENSITIZER OF HUMAN CERVICAL-CANCER CELLS

Paclitaxel is an exciting chemotherapeutic agent active in a variety o f malignant tumors. This study was designed to explore the radiosensit izing potential of paclitaxel in human cervical cancer cell lines. The cell lines ME180, SiHa, and MS751 were evaluated. Experiments were pe rformed in the proliferative phase of growth. Paclitaxel doses were tr eated at 0.01x, 0.02x, 0.03x, 0.04x, and 0.05x peak plasma concentrati on (PPC) in ME180 and 0.001x, 0.002x, 0.003x, 0.004x, and 0.005x PPC i n SiHa and MS751. Radiation (RT) doses of cobalt-60 were 0, 2, 4, 6, 8 , and 10 Gy. In the combination group RT was given 48 hr after paclita xel treatment. To allow for median effect analyses, combination doses were kept at a fixed ratio: 0.01x/2 Gy, 0.02x/4 Gy, 0.03x/6 Gy, 0.04x/ 8 Gy, and 0.05x/10 Gy for ME180 and 0.001x/2 Gy, 0.002x/4 Gy, 0.003x/6 Gy, 0.004x/8 Gy, and 0.005x/10 Gy in MS-751 and SiHa. Adenosine triph osphate bioluminescence was performed on Day 7 after treatment and com pared to untreated controls. Dose-response data were fit to the linear quadratic model and mean inactivation dose D was calculated. Data ana lysis with t test was performed. The median effect principle was used to evaluate the nature of the interaction between the two therapeutic modalities. Paclitaxel increased radiation cytotoxicity in all three c ell lines. Mean inactivation D values for RT versus combination were 6 .70 (+/-0.15) and 4.33 (+/-0.43) (P = 0.004) in ME180, 6.08 (+/-0.70) and 4.54 (+/-0.093) (P = 0.033) in MS751, and 7.03 (+/-0.46) and 5.97 (+/-0.51) (P = 0.034) in SiHa. The interaction of paclitaxel and RT wa s found to be supraadditive in ME180 and SiHa and subadditive in MS751 . We conclude that paclitaxel has modest radiation-sensitizing effects in cervical cancer cell lines and that further clinical trials should be considered. (C) 1995 Academic Press, Inc.