1. ¹CRC Department of Medical Oncology, Beatson Oncology Centre, Western Infirmary, Dumbarton Road, Glasgow G11 6NT, UK
2. ²Department of Clinical Biochemistry, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK
3. ³Department of Medical Oncology, St George's Hospital, Blackshaw Road, London SW17 0QT, UK
4. ⁴Section of Medicine, The Royal Marsden Hospital, Downs Road, Sutton, Surrey, SM2 5PT, UK
5. ⁵Biological Research Department, Leo Pharmaceutical Products, DK-2750 Ballerup, Denmark
6. ⁶Medical Department, Leo Pharmaceutical Products, DF-2750 Ballerup, Denmark

Correspondence: Dr TRJ Evans, CRC, Department of Medical Oncology, University of Glasgow, Beatson Laboratories, Switchback Road, Glasgow G61 1BD, UK. E-mail: J.Evans@beatson.gla.ac.uk

Received 28 August 2001; Revised 7 December 2001; Accepted 28 December 2001.

Abstract

Inoperable cancer of the exocrine pancreas responds poorly to most conventional anti-cancer agents, and new agents are required to palliate this disease. Seocalcitol (EB1089), a vitamin D analogue, can inhibit growth, induce differentiation and induce apoptosis of cancer cell lines in vitro and can also inhibit growth of pancreatic cancer xenografts in vivo. Thirty-six patients with advanced pancreatic cancer received once daily oral treatment with seocalcitol with dose escalation every 2 weeks until hypercalcaemia occurred, following which patients continued with maintenance therapy. The most frequent toxicity was the anticipated dose-dependent hypercalcaemia, with most patients tolerating a dose of 10–15 g per day in chronic administration. Fourteen patients completed at least 8 weeks of treatment and were evaluable for efficacy, whereas 22 patients were withdrawn prior to completing 8 weeks' treatment and in 20 of these patients withdrawal was due to clinical deterioration as a result of disease progression. No objective responses were observed, with five of 14 patients having stable disease in whom the duration of stable disease was 82–532 days (median=168 days). The time to treatment failure (n=36) ranged from 22 to 847 days, and with a median survival of approximately 100 days. Seocalcitol is well tolerated in pancreatic cancer but has no objective anti-tumour activity in advanced disease. Further studies are necessary to determine if this agent has any cytostatic activity in this malignancy in minimal disease states.