Anastrozole. A review of its use in the management of postmenopausal women with advanced breast cancer.
Anastrozole is a new oral nonsteroidal aromatase inhibitor indicated for the second-line endocrine treatment of postmenopausal women with advanced breast cancer. In postmenopausal women, anastrozole significantly reduces plasma estrogen levels; maximal suppression is achieved at dosages > or = 1 mg/day and levels remain suppressed during long term therapy. In two phase III clinical trials, anastrozole 1 or 10 mg/day showed similar clinical efficacy to that of oral megestrol (megestrol acetate) 160 mg/day in postmenopausal women with advanced breast cancer. Primary end-points [including time to disease progression (120 to 170 days) and overall response rates (complete and partial response and stable disease lasting > or = 24 weeks: 29 to 37%)] and secondary end-points [time to treatment failure (115 to 168 days) and duration of response (257 to 261 days)] did not differ significantly between treatment groups. However, a significant survival advantage was observed in patients treated with anastrozole 1 mg/day compared with megestrol in a follow-up combined analysis of patients enrolled in both studies (median time to death 26.7 vs 22.5 months). Quality of life parameters were generally improved to a similar extent in all treatment groups. Anastrozole is generally well tolerated in the majority of patients, the most common adverse events being gastrointestinal (GI) disturbances (incidence 29 to 33%). These events are generally mild or moderate and transient. Other adverse events reported with anastrozole include headache (< or = 18%), asthenia (< or = 16%), pain (< or = 15%), hot flushes and bone pain (both < or = 12%), back pain and dyspnoea (both < or = 11%) and peripheral oedema (< or = 9%). GI disturbance tended to be more common with anastrozole than megestrol, particularly at the 10 mg/day dosage; however, compared with megestrol, anastrozole is less frequently associated with weight gain.


CONCLUSIONS
Anastrozole, with its apparent survival advantage versus megestrol (demonstrated in a combined analysis of phase III studies), convenient once daily oral administration and acceptable short term tolerability profile, is a second-line treatment option for postmenopausal patients with tamoxifenrefractory advanced breast cancer. The results of ongoing comparative trials with tamoxifen will determine the relative efficacy of anastrozole as first-line endocrine therapy for advanced breast cancer and as adjuvant therapy for early disease. In addition, direct comparative studies are required to determine the efficacy of anastrozole relative to that of other oral aromatase inhibitors such as letrozole and vorozole.
Wiseman
L R
LR
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
Adkins
J C
JC
D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D009570:Nitriles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D017698:Postmenopause; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole