This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Burch, P. A. Articles by Loprinzi, C. L. Search for Related Content PubMed PubMed Citation Articles by Burch, P. A. Articles by Loprinzi, C. L. Social Bookmarking                            What's this?

Prostate-Specific Antigen Decline After Withdrawal of Low-Dose Megestrol Acetate

Mayo Clinic, Rochester, MN

To the Editor: A reduction in prostate-specific antigen (PSA) levels after withdrawal of nonsteroidal antiandrogens was first reported by Scher and Kelly in 1993.¹ Other reports confirming this finding soon followed.² This phenomenon may also be seen with the withdrawal of therapeutic doses of megestrol acetate.^3,4 We recently observed a patient who experienced a PSA response to the discontinuation of low-dose megestrol acetate, which had been administered to control hot flashes.

At the age of 60, our patient presented with clinically localized adenocarcinoma of the prostate (April 1987). He was treated with definitive radiation therapy. Three years later (May 1990), he developed osseous metastasis and underwent bilateral orchiectomy plus continuous flutamide treatment. Three years after his orchiectomy (April 1993), megestrol acetate 20 mg twice daily was prescribed for hot flashes.⁵ Figure 1 shows his serum PSA levels from June 1990 through September 1998. There was no response to the withdrawal of flutamide when the PSA reached 1.1 ng/mL. Six months later, the PSA value reached 5.3 mg/mL and his megestrol acetate was discontinued. In 2 months, the PSA value dropped to 1.9 ng/mL; when last checked, 6 months after megestrol acetate was stopped, it was 0.66 ng/mL.

View larger version (12K): [in this window] [in a new window]   Fig 1. PSA levels over time.

Currently, more patients are receiving second- and third-line treatments on the basis of PSA changes. Some of these treatments may be associated with unwanted side effects. Clinicians should recognize that even small doses of megestrol acetate, an agent with both progestational activity and antiandrogenic activity, might have an impact on PSA values. In this patient, discontinuation of all of his antiandrogens made the consideration of additional treatment unnecessary at this time.

This experience begs the question of whether low doses of megestrol acetate might be detrimental in patients with prostate cancer and, thus, ought not be used for control of hot flashes in such patients. We do not believe that this case provides a particular insight into whether low doses of megestrol acetate have any substantial impact upon the survival of patients with prostate cancer. There are data that demonstrate that higher doses of this drug do seem, in some men, to result in modest antitumor activity in this disease process.⁶ There is precedence that hormone withdrawal responses may be observed with antitumor agents in hormonally responsive cancers. In addition to the known antitumor activity seen with the withdrawal of previously effective antiandrogen therapy for prostate cancer,⁷ similar results can be observed in breast cancer with the withdrawal of the antitumor agents, diethylstilbestrol, or tamoxifen.

Given this potential but unproven risk associated with the use of megestrol acetate for treating hot flashes in men with prostate cancer, as is possible with basically any agent we prescribe for basically any condition, it seems appropriate that patients be warned of such uncertain risks. Nonetheless, given the major problem that hot flashes can can cause,⁸ the documentation that patients are clearly willing to undergo potential risk for the relief of hot flashes,⁹ and the knowledge that megestrol acetate can diminish hot flashes by approximately 80%,⁵ it does seem reasonable to use megestrol acetate in such patients. However, if there are increasing serial PSA levels in patients who receive megestrol acetate, it is reasonable to consider discontinuation of this hormonal drug.

REFERENCES

1. Scher HI, Kelly WK: Flutamide withdrawal syndrome: Its impact on clinical trials in hormone-refractory prostate cancer. J Clin Oncol 11:1566-1572, 1993[Abstract/Free Full Text]

2. Small EJ, Srinivas S: The antiandrogen withdrawal syndrome: Experience in a large cohort of unselected advanced prostate cancer patients. Cancer 76:1428-1434, 1995[Medline]

3. Dawson NA, McLeod DG: Dramatic prostate specific antigen decrease in response to discontinuation of megestrol acetate in advanced prostate cancer: Expansion of the antiandrogen withdrawal syndrome. J Urol 153:1946-1947, 1995[Medline]

4. Wehbe TW, Stein BS, Akerley WL: Prostate-specific antigen response to withdrawal of megestrol acetate in a patient with hormone-refractory prostate cancer. Mayo Clin Proc 72:932-934, 1997[Abstract]

5. Loprinzi CL, Michalak JC, Quella SK, et al: Megestrol acetate for the prevention of hot flashes. N Engl J Med 331:347-352, 1994[Abstract/Free Full Text]

6. Oh WK, Kantoff PW: Management of hormone refractory prostate cancer: Current standards and future prospects. J Urol 160:1220-1229, 1998[Medline]

7. Dupont A, Gomez Jl, Cusan L, et al: Response to flutamide withdrawal in advanced prostate cancer in progression under combination therapy. J Urol 150:908-913, 1993[Medline]

8. Quella S, Loprinzi CL, Dose AM: A qualitative approach to defining "hot flashes" in men. Urol Nurs 14:155-158, 1994[Medline]

9. Couzi RJ, Helzlsouer KJ, Fetting JH: Prevalence of menopausal symptoms among women with a history of breast cancer and attitudes toward estrogen replacement therapy. J Clin Oncol 13:2737-2744, 1995[Abstract]

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Burch, P. A. Articles by Loprinzi, C. L. Search for Related Content PubMed PubMed Citation Articles by Burch, P. A. Articles by Loprinzi, C. L. Social Bookmarking                            What's this?