Hormone stimulation and chemotherapy in advanced prostate cancer: preliminary results of a prospective controlled clinical trial.
Preliminary evidence suggests that the sensitivity of endocrine-dependent neoplasms to chemotherapy may be enhanced by transient hormonal stimulation of tumor growth. To test this concept, we are conducting a prospective controlled trial in men with stage D2 prostate cancer who have relapsed following orchiectomy. All patients are continuously treated with aminoglutethimide and hydrocortisone to lower adrenal androgen secretion plus cyclic chemotherapy. Patients in the stimulation arm receive, in addition, the synthetic androgen fluoxymesterone for 3 days before and on the day of chemotherapy. Of 41 patients entered to date, 26 are evaluable. Twenty-one (81%) obtained either an objective remission or stabilization of disease with a mean duration of 9+ months and 10 patients still responding. Thus far, the response rate is similar in the control and stimulation groups. Androgen administration was associated with a rise in acid phosphatase and usually a modest flare of symptoms except for 2 patients who developed spinal cord compression. These preliminary data indicate that the combination of aminoglutethimide and chemotherapy has a potent antitumor effect on advanced prostate cancer refractory to orchiectomy. A large number of patients and a longer follow up are needed to assess whether transient androgen administration potentiates the effect of chemotherapy.
D000135:Acid Phosphatase / Q000097:blood; D000368:Aged; D000616:Aminoglutethimide / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002369:Castration; D056486:Chemical and Drug Induced Liver Injury; D002986:Clinical Trials as Topic; D005474:Fluoxymesterone / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D011897:Random Allocation; D013117:Spinal Cord Compression / Q000139:chemically induced; D014555:Urination Disorders / Q000139:chemically induced
D000616:Aminoglutethimide; D005474:Fluoxymesterone; D000135:Acid Phosphatase; D006854:Hydrocortisone