There has been some positive news coming out of the ASCO conference in Florida this past week. One of the most significant pieces of positive news deals with the results of a phase I-II trial of the drug known as MDV3100. Basically, more than half of subjects in the study with castration-resistant prostate cancer responded to the investigational drug, MDV3100 which is an androgen receptor antagonist. Normally, castrate resistant prostate cancer patients do not respond androgen antagonist drugs.

MDV3100 is an investigative drug not available in the market place and the data and conclusion discussed comes solely from an abstract that was presented as a poster at this conference. This data and its conclusions should be considered to be preliminary until published and reviewed in a peer-reviewed journal.

    What The Poster Said:

A majority of patients on oral MDV3100 had at least a 50% reduction in PSA values, and the proportion of patients with favorable circulating tumor cell counts increased. Additionally, a majority of subjects with soft-tissue lesions and bone metastases had stable disease or better response to the drug.

MDV3100 not only blocked the androgen receptor, but it also inhibited the androgen receptor functioning by preventing nuclear translocation of the receptor and DNA binding. MDV3100 demonstrated activity in models of bicalutamide-resistant (casodex resistant ) prostate cancer.

The trial, which was a phase I-II clinical trial, involved 114 subjects with advanced and metastatic prostate cancer. Three fourths of the patients had received more than one prior hormonal therapy, and 49 had received chemotherapy prior to entering this study.

Snce the general purpose of phase I and II is to determine safe dosing, the trial began with evaluation of MDV3100 at various doses ranging from 30 to 600 mg/d in groups of three to six patients.

Serum PSA was measured at baseline and every four weeks thereafter. Circulating tumor cells were measured at baseline, week four, and week 12. All subjects had CT/MRI imaging every 12 weeks, and a subset of 16 patients had PET imaging to assess uptake of FDG and

[18-F]-fluorodihydrotestosterone (FDHT).

It was reported that 37 of 65 chemotherapy-naive patients and 22 of 49 chemotherapy-experienced patients had at least a 50% decrease in serum PSA from baseline to week 12.

A circulating tumor count of <5/7.5 mL of blood was defined as favorable, and higher counts were unfavorable. Of 101 patients with data on circulating tumor counts, 56 of 61 (92%) with favorable counts at baseline maintained the favorable status at week 12.Additionally, 21 of 43 patients with unfavorable baseline cell counts converted to favorable status.At week 12, six of 48 patients with soft-tissue lesions at baseline showed a partial response, and 30 had stable disease. Of 83 patients who had bone metastases at baseline, 52 had stable disease at week 12.PET scans revealed decreased uptake of FDHT in all 16 patients and decreased FDG uptake in 14 of 16.Dr. Scher from Memorial Sloane Kettering Medical Center in New York City, the senior investigator, reported that MDV3100 was well tolerated by the study subjects. The most commonly reported adverse event was fatigue, which led to one patient's to leave the study. Two of three patients who received the 600-mg dose had dose-limiting toxicity developed seizures and a rash while one subject receiving 360 mg/d also had a seizure ( this subject was taking other medications that could have caused the seizures).Dr. Scher said that additional investigations using MDV3100 will continue at a dose of 240 mg/d.Those of us who are castrate resistant might give consideration to monitoring when the next phase of trials will begin. Prior to this, these results must be released in a peer review journal and be evaluated by the FDA before any additional trials can be designed.Primary source: ASCO: Genitourinary Cancers SymposiumJoel T Nowak MA, MSW [/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]