>>In light of today's EMEA warning on toremifene, does anyone who follow GTXI aware of any data from acapodene's QT prolongation studies?<<
What little is around seems to be here:
>>The Prostate Journal
Volume 1 Issue 4, Pages 185 - 189
Published Online: 5 Jan 2002
Blackwell Science Inc
Phase II Trial of the Antiestrogen Toremifene for Androgen-Independent Prostate Cancer
Matthew R. Smith, MD, PhD,* Philip W. Kantoff, MD, † William Oh, MD † Grace Elson,* Judith Manola, PhD, † Margaret McMullin, RN,* Joseph Jacobsen, MD, ‡ Adam Brufsky, MD, PhD, § Donald Kaufman, MD*
*Massachusetts General Hospital, Boston, Massachusetts, U.S.A. † Dana Farber Cancer Institute, Boston, Massachusetts, U.S.A. ‡ North Shore Cancer Center, Peabody, Massachusetts, U.S.A. § University of Pittsburgh Cancer Center, Pittsburgh, Pennsylvania, U.S.A.
Address correspondence and reprint requests to: Matthew R. Smith, MD, PhD, Massachusetts General Hospital, Cox 640, 100 Blossom St., Boston, MA 02114, U.S.A.
ABSTRACT
Objectives: Estrogen receptors are expressed in healthy and malignant prostate epithelium. Previous studies of the antiestrogen tamoxifen (20–100 mg po qd) for recurrent or metastatic prostate cancer (CaP) reported response rates of 0–23%. These studies may have underestimated the activity of antiestrogens, however, because of their reliance on insensitive clinical and radiographic response criteria. In addition, treatment-related increases in androgen levels among men who initiated treatment with noncastrate testosterone levels may have confounded the results. The aims are to evaluate the activity of the antiestrogen toremifene, a triphenylethylene derivative antiestrogen related chemically and pharmacologically to tamoxifen, in men with androgen-independent CaP using prostate specific antigen (PSA) response criteria and to determine the effect of toremifene treatment on serum testosterone levels in castrated men.
Materials and Methods: Fifteen men (median age 71 years; median PSA 58.5 ng/ml) with castrate testosterone levels, no disease-related symptoms, and rising PSA after androgen deprivation and antiandrogen withdrawal were treated with toremifene, 60 mg po qd, until it was determined that the patient was not responding to treatment. Nonresponse to treatment was defined as symptomatic disease progression or a PSA level 150% study nadir on two determinations at least 4 weeks apart. Response was defined as >50% PSA decrease on two determinations at least 4 weeks apart.
Results: Twelve men were evaluable for response. Median time to determination of nonresponse to treatment was 16 weeks (range 8 to 19 weeks). There were no responses to treatment (response rate 0%; 95% confidence interval 0–22%). Treatment did not significantly change serum testosterone levels.
Conclusions: These results indicate that toremifene is inactive for the treatment of androgen-independent CaP and suggest that antiestrogens should not be used routinely as secondary hormonal therapy. The treatment of castrated men with toremifene does not significantly change serum testosterone levels.<<
The Google hit gets a snippet of the stuff in the main body: "Conclusions: These results indicate that toremifene is .... vascular toxicity ( QTc prolongation) in 3 (23%). of 13 men. Two (33%) of six men treated with . . ."
Note the Acapodene dosage is 80mg, but I don't know what the total exposure would be in the different indications. Definitely a major concern, and I'm a bit surprised the carnage isn't worse. I dodged a bullet here. I have this in my charity portfolio, and had a sold put position a couple of days ago. But I closed it out for a modest gain. Lucky, for once.
Cheers, Tuck |
