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Chemotherapy

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Conventional treatment

1998

Bernsen MR, Van Der Velden AW, Everse LA, Dullens HF, Den Otter W, Heintz AP. Interleukin-2: hope in cases of cisplatin-resistant tumours. Cancer Immunol Immunother. 1998 Mar;46(1):41-7. To establish whether or not local low-dose recombinant interleukin-2 (rIL-2) therapy might result in therapeutic benefit for ovarian cancer patients treated with cisplatin, the antitumour effects of rIL-2 and of combined treatment with cisplatin and rIL-2 in a mouse ovarian tumour (MOT) model were studied. In addition, some possible mechanistic aspects underlying the observed antitumour responses were analysed. MOT cells were injected i.p. into syngeneic, immunocompetent, female C3HeB mice. Tumour-bearing mice received i.p. treatment with cisplatin, rIL-2 or both. The MOT tumour appeared to be hardly responsive to treatment with cisplatin only or rIL-2 only. In contrast, combined local treatment with low doses of cisplatin (1 and 5 mg/kg body weight) and rIL-2 (60000 U/day) resulted in an effective antitumour response in MOT-bearing mice. Complete rejection of the i.p. (local) tumour occurred in up to 60% of the cases. In vitro studies showed that cisplatin and rIL-2 do not have cumulative direct toxic effects on MOT cells. Mice cured after combined treatment with cisplatin and rIL-2 were not able to reject a rechallenge with tumour cells, indicating that these mice had not developed immunity to the tumour. Analysis of tumour-associated leucocytes, however, showed that combined treatment with cisplatin and rIL-2 did result in enhanced non-specific cytolytic activity of peritoneal leucocytes. We have thus demonstrated that, in the MOT model, combined local treatment with low doses of cisplatin and of rIL-2 is far more effective than therapy with cisplatin alone. Non-specific cytotoxicity of leucocytes appears to be involved in antitumour responses induced by combined treatment with cisplatin and rIL-2. These results suggest that, in human ovarian carcinoma, much better results may be obtained with the combined treatment of cisplatin and low (non-toxic) doses of rIL-2 than with cisplatin only. This may also apply to cisplatin-resistant ovarian carcinoma.

2003

Spoormakers TJ, Klein WR, Jacobs JJ, Van Den Ingh TS, Koten JW, Den Otter W. Comparison of the efficacy of local treatment of equine sarcoids with IL-2 or cisplatin/IL-2. Cancer Immunol. Immunother. (2003) 52, 179 Local interleukin-2 (IL-2) is effective in a number of experimental animal models and in veterinary and human cancer patients without discomforting side effects. The primary goal of this study was to compare the therapeutic effects and side effects of the local intratumoral administration of five or ten low doses of IL-2 with those of a combination of cisplatin and a single high dose of IL-2 in the treatment of equine sarcoids. The therapeutic effect (complete and partial regression) of local cisplatin together with a single high dose of IL-2 was significantly better than the combined effect of low doses of local IL-2 administered daily over 5 or 10 days (80% and 43%, respectively; P=0.02). Cisplatin/IL-2 and low doses of IL-2 induced 53% and 14% complete regressions, respectively ( P=0.02). Histological changes after cisplatin/IL-2 treatment were far more pronounced than after IL-2 only treatment and in several cases showed an enormous eosinophilic infiltrate. Publication Types: Clinical Trial, Phase I, Phase II

Conventional treatment

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Our research is supported by Stichting ter bevordering van het onderzoek in de Experimentele Pathologie en in het bijzonder in de TumourImmunologie. Stichting EPTI, IJselstein, The Netherlands