Effects of treatment with abiraterone acetate on body composition

Data from early Phase I/II clinical trials of abiraterone acetate in men with metastatic, castration-resistant prostate cancer (mCRPC) suggest that combining abiraterone acetate with dexamethasone limits loss of muscle mass and visceral fat. Low-dose dexamethasone was used rather than prednisone in these early clinical trials.

In early-stage clinical trials of abiraterone acetate, some patients were followed with serial CT scans, and it has proved possible to use those scans to examine the cross-sectional areas of total fat, visceral fat, and muscle. (It is, of course, well known that standard forms of androgen deprivation therapy (ADT) reduce muscle mass. Men being treated in these early clinical trials of abiraterone acetate all continued on ADT while being treated with abiraterone acetate, so one of the items of interest in these early trials was whether treatment with abiraterone acetate would further reduce muscle mass (known as “sarcopenia”).

In these Phase I/II clinical trials, men were initially treated with abiraterone acetate alone and then low-dose dexamethasone (at 0.5 mg/d) was added later.

Here is what Pezaro et al. report from their retrospective analysis of data from the CT scans:

  • 55 patients were treated, first with abiraterone acetate alone and then with abiraterone acetate + dexamethasone
    • Median time on abiraterone acetate alone was 7.5 months.
    • Median time of abiraterone acetate + dexamethasone was 5.4 months.
  • Some muscle loss was apparent while patients were on  treatment with abiraterone acetate alone
    • Maximal muscle loss of 4.3 percent was observed in men with a baseline body mass index (BMI > 30.
  • No further muscle loss was observed after the addition of dexamethasone.
  • Significant loss of visceral fat was evident while patients were on treatment with abiraterone acetate alone
    • 19.6 percent loss of visceral fat was observed in men with a baseline BMI > 30.
  • Addition of dexamethasone to the abiraterone acetate increased visceral fat, totqal fat, and BMI in all patients.

The authors state only that, “These changes could have important quality-of-life implications for men treated with abiraterone.”

It has never been entirely clear to The “New” Prostate Cancer InfoLink precisely why later clinical trials of abiraterone acetate were conducted with low-dose predisone as opposed to low-dose dexamethasone. Certainly there are differences in the levels of risk for side effects associated with use of these two different glucocorticoids; however, low-dose dexamethasone is commonly used in combination with other targeted agents used in the treatment of certain cancers (e.g., in combination with lenalidomide [Revlimid] in treatment of multiple myeloma). It is not as though the average medial oncologist is inexperienced in the use of dexamethasone.

It is possible that this decision was taken because urologists and urologic oncologists enrolling patients in the Phase III trials of abiraterone acetate would probably not have had experience in treating men using dexamethasone. However, The “New” Prostate Cancer InfoLink continues to wonder whether using low-dose dexamethasone (as opposed to prednisone) as the glucocorticoid of choice to combine with abiraterone acetate may actually be wise for many men in terms of their overall outcome.

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