9133 Background: Cancer cachexia is closely correlated with poor outcome and poor survival. RC is an oral ghrelin mimetic with orexigenic and anabolic activity. Methods: A phase II trial enrolled 81 patients with cancer, performance scores of 0–2, and weight loss of 5% or more within 6 months prior to enrollment at 17 sites in the US. Patients were randomized to treatment with two placebo (PL) or two 25 mg RC capsules taken once daily for 12 weeks. Outcome measures included lean body mass (LBM), total body mass (TBM) by DEXA (central reading), scale weight, handgrip strength (HS) and QOL measures. Biochemical markers included IGF-1 and IGFBP-3. In the per protocol analysis (32 RC, 28 PL) more than 20 cancer types were represented; the most common were lung (n=13) and colorectal cancer (n=15). The two treatment groups were balanced at baseline except for (RC vs PL, respectively): gender (66 % male vs 57 %), TBM (60.9 kg vs 65.3 kg), and HS (53.8 kg vs 56.6 kg). The analyses (repeated measures ANOVA without imputation) included all available data from the patients. Results: TBM and LBM (primary endpoint at 8 wks) were significantly increased vs. PL at wks 4 and 8 and at wks 4, respectively. The magnitude of the increase vs. baseline was stable from wk 4 through wk 12 during RC treatment for both TBM and LBM. HS was increased at significantly at wk 8. IGF-1 and IGFBP-3 significantly increased at wks 4, 8, and 12. No significant differences were found on the QOL or scale weight measures. RC was well tolerated. Patients having any AEs were 96% vs 87% and SAEs were 32% and 26% for RC and PL, respectively. The percent of patients and types of AEs were similar; possible exceptions included cardiac events and infections (11% vs 3% and 30% vs 42%, RC vs PL, respectively). Conclusions: In this randomized, double-blind, placebo-controlled trial, RC treatment led to improvements in LBM, TBM and HS. RC-1291 is a promising potential therapeutic agent for the treatment of cancer cachexia. No significant financial relationships to disclose.
The effect of hypoxia and hyperoxia on nucleoside triphosphate/inorganic phosphate, pO2 and radiation response in an experimental tumour model