by ecancer reporter Janet Fricker

Inecalcitol, a novel anti-cancer drug aimed at vitamin D receptors delivered "encouraging" results in the treatment of hormone refractory prostate cancer, reported a French abstract presented at the 22 nd EORTC-NCI-ACCR Symposium on Molecular Targets and Cancer Therapeutics (16 to 19 November,  Berlin, Germany).

Inecalcitol is an orally active agonist targeting the vitamin D receptor that is effective at inhibiting cancer cell proliferation and differentiation. The therapeutic rationale behind development is to add inecalcitol’s cytostatic potential to the established efficacy of treatments such as anti hormonal therapy and chemotherapy. There have been a number of prior attempts using products that target the vitamin D receptor as a treatment for prostate cancer, with the most recent using calcitriol (the natural active metabolite of vitamin D 3).  While calcitriol appeared active in early stage trials, it was unable to show clinical effectiveness in combination with docetaxel and prednisone when compared to placebo.   Inecalcitol is a synthetic derivative of calcitriol, developed to be ten times more potent and one hundred times less toxic.

The  phase IIa study, by Jacques Medioni and colleagues from Hôpital Européen Georges Pompidou (Paris, France) evaluated  54 patients with hormone refractory prostate cancer who had been enrolled in groups of three to six patients to test nine dose levels of inecalcitol (from 40 micrograms up to 8 milligrams per day) for a maximum of 18 weeks. Patients had an average age of 71 years, 83% had bone metastases and had a median average PSA levels of 31.7 nanograms per millilitre of blood.

Results showed that when inecalcitol was combined with docetaxel and prednisone, 83 % of patients responded to the treatment with a drop in PSA levels of 30% or more within three months of treatment. The figure, say the authors, compares favourably with the 65% response rate previously reported with use of docetaxel alone. Additionally, researchers found that the maximum tolerated dose of inecalcitol was 4000 micrograms a day, as none of patients treated at this level experienced side effects more serious than hypercalcaemia

 “The majority of men (in the study) had very advanced disease and, therefore, it is very encouraging to see PSA levels dropping in such a high proportion of patients and a time to biochemical relapse of nearly half a year,” said Medioni, adding that the study was in a small group of patients, making it difficult to extrapolate to the wider population of prostate cancer patients.

The next step, said investigators, with be for inecalcitol to be tested in patients in a larger phase II b trial expected to start in the second quarter of 2011.

Reference

J Medioni, G Deplanque, JM Ferrero, et al.  Dose finding of inecalcitol, a new VDR agonist, in combination with docetaxel-prednisone regimen for castrate-resistant prostate cancer (HRPC) patients. Abstract no 430. EORTC-NCI-AACR Symposium.