Dose-response trial of megestrol acetate in advanced breast cancer: cancer and leukemia group B phase III study 8741.
OBJECTIVE
To investigate whether dose escalation of megestrol acetate (MA) improves response rate and survival in comparison with standard doses of MA.


METHODS
Three hundred sixty-eight patients with metastatic breast cancer, positive and/or unknown estrogen and progesterone receptors, zero or one prior trial of hormonal therapy, and no prior chemotherapy for metastatic disease were prospectively randomized into three groups. The groups of patients received either MA 160 mg/d (one tablet per day), MA 800 mg/d (five tablets per day), or MA 1,600 mg/d (10 tablets per day).


RESULTS
Patient characteristics were well balanced in the three treatment groups. Three hundred sixty-six patients received treatment and were included in the analyses. The response rates were 23%, 27%, and 27% for the 160-mg, 800-mg, and 1,600-mg arms, respectively. Response duration correlated inversely with dose. Median durations of response were 17 months, 14 months, and 8 months for the 160-mg, 800-mg, and 1,600-mg arms, respectively. No significant differences in the treatment arms were noted for time to disease progression or for survival; survival medians were 28 months (low dose), 24 months (mid dose) and 29 months (high dose). The most frequent and troublesome toxicity, weight gain, was dose-related, with approximately 20% of patients on the two higher-dose arms reporting weight gain of more than 20% of their prestudy weight, compared with only 2% in the 160-mg dose arm.


CONCLUSIONS
With a median follow-up of 8 years, these results demonstrate no advantage for dose escalation of MA in the treatment of metastatic breast cancer.
Abrams
J
J
University of Maryland Cancer Center, Baltimore, MD, USA. AbramsJ@CTEP.nci.nih.gov
Aisner
J
J
Cirrincione
C
C
Berry
D A
DA
Muss
H B
HB
Cooper
M R
MR
Henderson
I C
IC
Panasci
L
L
Kirshner
J
J
Ellerton
J
J
Norton
L
L
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D019290:Megestrol Acetate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D011446:Prospective Studies; D015996:Survival Rate
D000970:Antineoplastic Agents; D019290:Megestrol Acetate