Enzastaurin is an investigational, multi-targeted therapy that is currently the focus of two global phase III clinical trials, one for the treatment of glioblastoma and one in non-Hodgkin’s lymphoma.
New preclinical data presented at the 2006 American Society of Clinical Oncology (ASCO) meeting have provided support for the oral agent’s activity across multiple cancer lines. Clinical results have also highlighted enzastaurin’s potential to enhance the benefit of standard-of-care chemotherapies such as Lilly’s Gemzar (gemcitabine HCl) and Alimta (pemetrexed), and Roche’s Xeloda (capecitabine), with manageable side effects.
Three presentations were made highlighting enzastaurin’s potential for additive or synergistic anticancer effects without excessive toxicity in advanced solid tumors including lung, breast, pancreas, and head/neck cancers. The data were gathered from three phase I studies that combined enzastaurin with Gemzar/cisplatin, Alimta and capecitabine.
Each study showed similar results, concluding in each case that the enzastaurin combination was generally well tolerated across all dose levels; and there were no observations of significant alterations in pharmacokinetics.
Further data on enzastaurin’s safety were published from a review of data gathered from three phase I and II studies, suggesting that enzastaurin is generally well tolerated across all doses and for extended durations.
Additional preclinical studies presented point toward enzastaurin’s in-vitro activity in certain non-small cell (NSCLC) and small cell cancer (SCLC) cell lines, as well as in chemo-resistant ovarian cancer cell types.
In the lung cancer study, researchers concluded that enzastaurin produced in-vitro growth inhibition of SCLC and NSCLC cell lines accompanied by modulation of GSK3-b, a protein involved in energy metabolism and neuronal cell development. This study also showed enzastaurin had synergistic growth inhibition when combined with Alimta in these cell lines.
The ovarian cancer study corroborated the use of GSK3-beta phosphorylation as a marker for PKC-beta activity in ovarian cancer models. This further indicates that taxane-resistant cells seemed to respond to enzastaurin treatment in low concentrations and further supported the study of enzastaurin to evaluate the benefit for women with taxane-resistant ovarian cancer.