The experimental neuroprotectant leukaemia inhibitory factor (LIF) does not compromise antitumour activity of paclitaxel, cisplatin and carboplatin

Boyle, FM; Beatson, C; Monk, R; Grant, SL; Kurek, JB

Author(s): Boyle, FM; Beatson, C; Monk, R; Grant, SL; Kurek, JB;
Details: Publication Year 2001-12,Volume 48,Issue #6,Page 429-434
Journal Title: CANCER CHEMOTHERAPY AND PHARMACOLOGY
Publication Type: Journal Article
Abstract: Purpose: Peripheral neuropathy caused by the anticancer agents cisplatin and paclitaxel is a significant dose-limiting toxicity of these drugs. The growth factor leukaemia inhibitory factor (LIF) has neuroprotectant activity in preclinical models of nerve injury and degeneration and is now in a phase II trial in chemotherapy-induced peripheral neuropathy (CIPN). It is therefore important to ensure that LIF neither inhibits the antitumour activity of these drugs, nor stimulates tumour growth. Methods: Mature female Dark Agouti rats were implanted subcutaneously with a mammary carcinoma, DAMA. It was confirmed that the tumour expressed LIF receptors by reverse transcriptase polymerase chain reaction. Paclitaxel was administered at a dose of 5 mg/kg daily for 6 days, cisplatin at a dose of 3 mg/kg twice weekly and carboplatin at a dose of 10 mg/kg twice weekly. The effect of LIF on tumour growth and response to chemotherapy was assessed at two doses (2 and 10 mug/kg per day). Peripheral neuropathy was assessed in terms of gait disturbance and tail-flick threshold. Results: Neither dose of LIF stimulated growth of control tumours. Mean tumour volumes were lower on day 14 in all paclitaxel-, cisplatin- and carboplatin-treated groups, compared to controls (ANOVA P<0.001). LIF did not interfere with this antitumour effect. Cisplatin- and paclitaxel-treated groups had developed increasing tail-Flick thresholds by day 14. These manifestations of sensory neuropathy were prevented by LIF administration. Conclusions: These results suggest that LIF may be safely used in human trials as a neuroprotectant for patients receiving cisplatin, paclitaxel and carboplatin without concern for impairment of antitumour effect.
Publisher: SPRINGER-VERLAG
Keywords: NERVE GROWTH-FACTOR; ROOT GANGLION NEURONS; BREAST-CANCER CELLS; FACTOR PREVENTS; NEUROPATHY; EXPRESSION; RECEPTOR; RAT; NEUROTOXICITY; INTERLEUKIN-6
Publisher's Version: https://doi.org/10.1007/s00280-001-0382-6
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2001-12-01 12:00:00