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 µg/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.
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Boyle, F.M., Beatson, C., Monk, R. et al. The experimental neuroprotectant leukaemia inhibitory factor (LIF) does not compromise antitumour activity of paclitaxel, cisplatin and carboplatin. Cancer Chemother Pharmacol 48, 429–434 (2001). https://doi.org/10.1007/s00280-001-0382-6
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DOI: https://doi.org/10.1007/s00280-001-0382-6