Activity of pm02734 against human breast and prostate tumors

4712 The novel investigational agent PM02734 is a member of the Kahalalide F family of compounds that display marked anttumor activity properties and is currently undergoing multicenter phase I clinical trials in Europe and the U.S. In this limited study, we implanted human tumors subcutaneously into athymic nude mice (N = 10) and allowed them to grow in situ until they reached a size of approximately 100 ± 15 mm 3 at which time animals were randomized and drug treatment commenced. We evaluated the effect of PM02734 individually against human breast (MX-1) and prostate (DU-145) tumors grown as xenografts in either female or male cohorts, respectively, when PM02734 was administered as a five-consecutive-day (QDx5) intravenous injection regimen. Interestingly, PM02734 QDx5 at a dose of 320-325 μg/kg/day abrogated, on average, growth of established tumors in both xenografts, and this effect was concurrent with treatment. In particular, the ratio of tumor sizes applicable to animals treated with drug relative to the vehicle control cohort on a percentage basis on Day 3 of dosing was 49% and 46% in breast and prostate xenografts, respectively. This tumor growth exhibited a high degree of statistical significance when compared to corresponding vehicle control groups in breast and prostate xenografts and remained statistically significant beyond the treatment schedule. In fact, tumor growth delay of drug- compared to vehicle-treated cohorts was approximately five and four days for breast and prostate tumor xenografts, respectively. Based on body weight measurements, treatment with PM02734 QDx5 appeared to be well-tolerated. In summary, PM02734 QDx5 demonstrates a rapid onset of tumor inhibition activity and a strong cytostatic effect judging from breast and prostate xenografts reported herein. Additional studies are ongoing.