Flutamide-associated liver toxicity during treatment with total androgen suppression and radiation therapy for prostate cancer.
OBJECTIVE
To examine the frequency and severity of toxicity associated with flutamide inpatients treated with total androgen suppression before and during pelvic radiation therapy (RT) for prostate cancer.


METHODS
Sixty-five patients with T2b-T4 prostate cancer received flutamide and goserelin acetate for 4 months, with RT beginning at the 3rd month. Treatment records including liver function test (LFT) results at baseline and during treatment were reviewed and toxicities noted.


RESULTS
In 30 (46%) of 65 patients, flutamide was discontinued prematurely. Primary reasons included elevation in LFT levels (n=14); gastro-intestinal toxicity (n=9); decreased hemoglobin level (n=2); patient refusal (n=2); and arthralgia, rash, and malaise (n=1 each). Hepatotoxicity generally was manifest as asymptomatic transaminase level elevation. Grade 3-4 hepatotoxicity was noted in four of 65 patients. Mean aspartase aminotransferase increased from 23 (baseline) to 67 U/L (during flutamide treatment) (P<.02); mean alanine aminotransferase level increased from 26 (baseline) to 94 U/L (during flutamide treatment) (P<.005).


CONCLUSIONS
Flutamide toxicity was common. LFTs should be monitored during flutamide therapy. The role of flutamide in this treatment regimen may need to be reevaluated.
Rosenthal
S A
SA
Department of Radiation Oncology, University of California, San Francisco, USA.
Linstadt
D E
DE
Leibenhaut
M H
MH
Andras
E J
EJ
Brooks
C P
CP
Stickney
D R
DR
Chang
G C
GC
Wolkov
H B
HB
Gilbert
R M
RM
D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000726:Androgen Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D004796:Clinical Enzyme Tests; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005485:Flutamide / Q000009:adverse effects* / Q000627:therapeutic use; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D017273:Goserelin / Q000627:therapeutic use; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000628:therapy*; D011879:Radiotherapy Dosage
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D017273:Goserelin; D005485:Flutamide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase