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

Cancer Chemother Pharmacol. 2001 Dec;48(6):429-34. doi: 10.1007/s00280-001-0382-6.


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 microg/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Carboplatin / pharmacology*
  • Cisplatin / pharmacology*
  • Drug Interactions
  • Female
  • Growth Inhibitors / pharmacology*
  • Infusions, Parenteral
  • Injections, Subcutaneous
  • Interleukin-6*
  • Leukemia Inhibitory Factor
  • Lymphokines / pharmacology*
  • Mammary Neoplasms, Experimental
  • Paclitaxel / pharmacology*
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / prevention & control
  • Rats


  • Antineoplastic Agents, Phytogenic
  • Growth Inhibitors
  • Interleukin-6
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • Lymphokines
  • Carboplatin
  • Paclitaxel
  • Cisplatin