goserelin and Diarrhea

In a recent study by the Casodex Combination Study Group, USA, patients in a flutamide (750 mg/day) plus LH-RH agonist group showed a high treatment failure rate, mainly due to flutamide-induced diarrhea and hepatotoxicity. Our current study was conducted to determine the optimal dose of flutamide for use in this type of combination therapy.. In a randomized, multicenter study, 30 patients (hormone untreated; stage C or D) were divided into 2 groups: flutamide 250 mg (125 mg x 2; 14 patients) and flutamide 375 mg (125 mg x 3; 16 patients, and each dose combined with either goserelin acetate (3.6 mg every 4 weeks) or leuprolide acetate (3.75 mg every 4 weeks). Goserelin and leuprolide were administered to patients in a 1:1 ratio. Flutamide monotherapy at a daily dose of 375 mg was determined to be the optimal dose in Japan in our previous phase II study. The endpoints of this pilot study were the objective response and adverse events during the 12-week treatment.. The objective response rate was 83.3% in the flutamide 250 mg group and 85.7% in the flutamide 175 mg group according to the Japanese response criteria for prostate cancer. Elevated PSA levels fell to within the normal range in 83.3% of the patients in the former group and in 93.3% of the patients in the latter group. One patient administered 250 mg of flutamide experienced diarrhea, while the serum GOT and/or GPT were elevated in 3 patients administered 250 mg of flutamide and 4 patients administered 375 mg of flutamide.. Based on the findings of this pilot study of maximal androgen-depletion therapy for advanced prostate cancer, 375 mg/day of flutamide is recommended in combination with an LH-RH agonist. Assessment of the effects of our recommended regimen on longer term survival, quality of life and antiandrogen withdrawal syndrome of patients treated requires additional patients and time for follow-up.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemical and Drug Induced Liver Injury; Diarrhea; Dose-Response Relationship, Drug; Flutamide; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms

In patients with locally advanced (bulky) carcinoma of the prostate, definitive radiotherapy is associated with a high rate of local recurrence. The Radiation Therapy Oncology Group (RTOG) has conducted several studies evaluating hormonal cytoreduction (used as an induction regimen) as a means of improving the local control rate. RTOG 85-19 tested an induction regimen consisting of a depot LH-RH agonist (Zoladex) and an antiandrogen (flutamide). Eligible patients were those with bulky primary lesions (stage B2 and C) with disease confined to the pelvis. Zoladex was administered every 29 days via a subcutaneous injection. Flutamide was given by mouth in a dose of 250 mg t.i.d. Administration of the drugs was initiated 2 months prior to start of radiotherapy and was terminated at completion of the radiotherapy course. Radiotherapy consisted of 180-200 rad/day, 4,400-4,500 rad to the regional lymphatics, and 6,500-7,000 rad to the prostate. The primary aim of the study was to evaluate the effectiveness and toxicity of the combined (hormonal cytoreduction plus definitive radiotherapy) regimen. Thirty-one patients were accessioned; 30 are analyzable. The drug-related toxicity appears acceptable. It included appearance of diarrhea before initiation of radiotherapy in two patients, nausea during the 2nd week of drug administration in two patients, and skin rash in three patients. These phenomena appear to be related to flutamide. Hot flashes were recorded in 17 patients. With a minimum follow-up of 2 years, clearance of the primary lesions (by clinical examination) was documented in 28 of 30 patients. During the 1st year, two of 30 patients died (of unrelated causes) with residual palpable tumors. The observed toxicity appears acceptable and the response rate encouraging. A phase III study comparing the tested regimen against radiotherapy alone appears warranted.

Topics: Buserelin; Diarrhea; Flutamide; Goserelin; Humans; Male; Prostatic Neoplasms; Radiotherapy