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Anti-inflammatory Treatment May Prolong Survival in Undernourished Patients with Metastatic Solid Tumors¹

Department of Surgery, Sahlgrenska Hospital, University of Göteborg, S-413 45 Göteborg, Sweden

Eicosanoids may be important factors for tumor cell proliferation, metastatic formation, and development of cancer cachexia. The present study has evaluated the effect of anti-inflammatory treatment on tumor progression in clinical cancer. Patients (n = 135) with insidious or overt malnutrition due to generalized malignancy (various kinds of solid tumors) and an expected survival of more than 6 months were randomized by a computer-based algorithm to receive placebo, prednisolone (10 mg twice daily), or indomethacin (50 mg twice daily) p.o. until death. Patient groups were stratified in the randomization procedure for sex, tumor type, stage, nutritional state, and previous tumor treatment, and biochemical, physiological, and some functional variables (Karnowsky index, fatigue and pain score). A majority of these variables was then registered during the follow-up. Indomethacin and prednisolone treatment maintained Karnowsky index, while placebo-treated patients experienced a decreased index. Indomethacin-treated patients suffered less pain and consumed less additional analgetics compared to the other patient groups. Indomethacin prolonged mean survival compared to placebo-treated patients from 250 ± 28 days to 510 ± 28 days (P < 0.05). Survival analysis on observations from all patients treated with either indomethacin or prednisolone demonstrated a significantly prolonged survival by anti-inflammatory treatment compared to placebo treatment (log rank, P < 0.03). The results suggest that not only may prostaglandin synthesis inhibition offer palliative support to patients with solid advanced cancer, but it may also impact on pathways that ultimately determine outcome.

¹ Supported in parts by Swedish Cancer Society Grants 93-B89-22XA, 2014-B92-06XCD, and 2014-B93-07XDD; Medical Research Council Grants B89-17X-00536-29B and B93-17X-08712-05B; the Tore Nilson Foundation; the Assar Gabrielsson Foundation (AB Volvo); the Jubileumskliniken Foundation; the Inga-Britt and Arne Lundberg Research Foundation; the Axel and Margaret Axöson Johnson Foundation; the Swedish and Göteborg Medical Societies; and the Medical Faculty, University of Göteborg.

² To whom requests for reprints should be addressed.

Received 4/28/94. Accepted 9/ 2/94.

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