Hybrigenics, a bio-pharmaceutical company listed on Alternext (Euronext) in Paris, with a focus on research and development of new cancer treatments and specialized in protein interactions, announced preclinical results demonstrating the potential of inecalcitol alone and in a synergistic combination with a cytotoxic platinum derivative, to inhibit the growth of a human hormone-dependent prostate cancer cell line. These results are presented at the 14th Vitamin D Workshop at Brugge in Belgium by Dr Ryoko Okamoto.
Dr Okamoto showed that inecalcitol was 11 times more potent than calcitriol, the naturally active metabolite of vitamin D, to inhibit the growth in vitro of the human hormone-dependent prostate cancer cell line named LNCaP. She also showed that 30 micrograms/mouse of inecalcitol three times per week for 11 weeks was well tolerated and that, by contrast, the maximum tolerated dose of calcitriol in mice was limited to 0.0625 micrograms/mouse. This means that inecalcitol was at least 480 times less toxic than calcitriol in the same experimental conditions. Dr Okamoto works in Prof Koeffler's Division of Hematology and Oncology at the Cedars-Sinai Medical Center of the UCLA School of Medicine.
In another set of experiments, inecalcitol was shown to be 25 times more potent in vitro on the same LNCaP human cell line than a platinum-based cytotoxic compound. When combined together, inecalcitol and the platinum derivative exerted synergistic inhibitory effects in vitro at low concentrations. Inecalcitol and the platinum derivative were subsequently administered in small non-toxic doses to mice inoculated with human LNCaP cells: each compound alone reduced tumour growth by half over 6 weeks. In combination, they produced a statistically significant decrease of 65 per cent.
"Although still preliminary, these results from a leading international laboratory in the field of cancer applications of vitamin D analogues are very promising for two reasons: 1) inecalcitol may be active against hormone-dependent prostate cancer (and not only against hormone-refractory prostate cancer against which it is currently being developed in combination with Taxotere chemoterapy), and 2) inecalcitol might also be successfully combined with platinum-based chemotherapeutics (and not only with taxanes like Taxotere)," said Remi Delansorne, Hybrigenics' CEO.