Lack of thermal enhancement for taxanesin vitro

Abstract

The taxanes represent a new class of clinical chemotherapeutic agents. A series of in vitro studies were independently of each other initiated in two different institutes (Amsterdam and Madison) to test the hypothesis that hyperthermia might enhance the cytotoxicity of taxanes. Clonogenic capacity experiments (Amsterdam) included the exposure of R1- and SW 1573-cells to 1, 4, or 24 h of paclitaxel with heat 43 degrees C x 60 min in the last hour of drug treatment or at 24, 48 as well as 72 h post drug treatment. Survival assay experiments (Madison) included the exposure of L-929-cells to paclitaxel and docetaxel for 24 h with heat 41.8 degrees C x 60 min the first or last hour of drug treatment as well as 24 and 48 h post treatment. No thermal enhancement of cytotoxicity for the taxanes was observed in these human and murine cell lines, with congruent data in both institutes. In addition, high performance liquid chromatography studies at 41.8 degrees C and 43 degrees C demonstrated paclitaxel and docetaxel were heat stable.

Hyperthermic Enhancement of the Apoptotic and Antiproliferative Activities of Paclitaxel

“…In fact, increased intracellular penetration at hyperthermic temperatures had been demonstrated for the taxane compounds [20], even though they acknowledged that the rate of drug penetration depends on the type of tumor cell under investigation. It is therefore not surprising that a study by Rietbroek et al [21] revealed lack of thermal enhancement of antitumor effect of taxanes. The disparity occurred from the use of different tumor cells.…”

The Cytotoxic Effect of Combined Hyperthermia and Taxane Chemotherapy on Ovarian Cancer Cells: Results of an in vitro Study

“…Concerning paclitaxel, in an in vitrostudy of murine breast cancer, Othman et al [19] found a synergistic benefit when it was used concurrently with hyperthermia at 43°C for 1 h at 10 µml/l. However, Rietbroeck et al [17] observed no thermal enhancement of paclitaxel-induced cytotoxicity with three different cell lines, with exposure temperatures of 41.8 and 43°C and drug concentrations ranging from 0.001 to 10 µ M . Leal et al [20] have studied the interaction of hyperthermia with paclitaxel in human breast adenocarcinoma cells.…”

“…All studies had an exposure duration of 1 h, and the incubation temperature ranged from 41.8 to 43°C. Different drug concentrations have been studied: 50 n M [16], 0.2 to 12 µ M [17] and 0 to 50 ng/ml [18]. None of the studies found an increase of cytotoxic effects of docetaxel with hyperthermia.…”

“…In our study, hyperthermia does not increase the cytotoxic effect of taxanes, except when docetaxel is used for 30 min. Three in vitrostudies have looked for an interaction between hyperthermia and docetaxel (table 2) [16,17,18]. All studies had an exposure duration of 1 h, and the incubation temperature ranged from 41.8 to 43°C.…”

Docetaxel and hyperthermia: Factors that modify thermal enhancement

“…There are conflicting reports of the interaction of docetaxel with hyperthermia. In vitro studies have shown no thermal enhancement [19,20] of docetaxel at 438C. Our previous in vivo study demonstrated thermal enhancement at 41.58C [8].…”