An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane

@article{Buzdar2002AnOO,
  title={An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane},
  author={Aman U. Buzdar and John F R Robertson and Wolfgang Eiermann and Jean Marc Nabholtz},
  journal={Cancer},
  year={2002},
  volume={95}
}
The newer generation, nonsteroidal aromatase inhibitors (AIs) anastrozole and letrozole have shown superior efficacy compared with tamoxifen as first‐line treatments and compared with megestrol acetate as second‐line therapy in postmenopausal women with advanced breast carcinoma. In an open‐label, Phase II trial, it was reported that exemestane showed numerical superiority compared with tamoxifen for objective response and clinical benefit. Because these agents ultimately may be administered… 
Aromatase inhibitors: a safety comparison
TLDR
It is important that differences in the safety profiles of the third-generation AIs are understood, as the available AIs have similar efficacy and it is likely that safety and tolerability profiles will have an impact on agent selection in clinical practice.
New aromatase inhibitors as second‐line endocrine therapy in postmenopausal patients with metastatic breast carcinoma
TLDR
A pooled analysis including all the Phase III trials published between 1996 and 2004 evaluating the AIs approved or not by the Food and Drug Administration and the European Agency for the Evaluation of Medical Products as second‐line endocrine therapy (ET) for patients with MBC is performed.
The adjuvant endocrine treatment revolution: focus on anastrozole
  • R. Jakesz
  • Biology, Medicine
    Expert opinion on drug metabolism & toxicology
  • 2006
TLDR
The use of anastrozole is now widely accepted in advanced breast cancer and its superior efficacy and tolerability to tamoxifen has recently been demonstrated in early breast cancer.
Long-term safety of aromatase inhibitors in the treatment of breast cancer
  • J. Nabholtz
  • Medicine
    Therapeutics and clinical risk management
  • 2008
TLDR
The results from the available adjuvant AIs trials are explored with a particular emphasis on safety profiles, quality of life, and therapeutic index, helping to define the present role of AIs in the adjUvant management of postmenopausal patients with breast cancer.
Are aromatase inhibitors superior to antiestrogens?
  • A. Howell, A. Buzdar
  • Medicine, Biology
    The Journal of Steroid Biochemistry and Molecular Biology
  • 2005
Data from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trial
  • A. Buzdar
  • Medicine
    Clinical Cancer Research
  • 2004
TLDR
Anastrozole should be considered a valid alternative option to tamoxifen for adjuvant hormonal treatment in all postmenopausal women with hormone receptor-positive early breast cancer.
Aromatase inhibitors: changing the face of endocrine therapy for breast cancer.
  • A. Buzdar
  • Medicine, Biology
    Breast disease
  • 2005
TLDR
The data indicate that the third-generation AIs provide superior recurrence benefits to tamoxifen in the adjuvant setting, with a reduction in serious adverse events such as endometrial cancer and thromboembolic events associated with the AIs compared with tamoxIFen.
Pharmacokinetics and dose finding of a potent aromatase inhibitor, aromasin (exemestane), in young males.
TLDR
Exemestane is a potent aromatase inhibitor in men and an alternative to the choice of available inhibitors and long-term efficacy and safety will need further study.
Adjuvant aromatase inhibitor therapy for early breast cancer: A review of the most recent data
  • G. Grana
  • Medicine, Biology
    Journal of surgical oncology
  • 2006
TLDR
Results from randomized trials of the third‐generation aromatase inhibitors, anastrozole, letrozoles and exemestane, demonstrating improved efficacy compared with tamoxifen and favorable tolerability profiles are discussed in this review.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 91 REFERENCES
Letrozole, a new oral non-steroidal aromastase inhibitor in treating postmenopausal patients with advanced breast cancer. A pilot study.
TLDR
Letrozole appears to be a very promising new antiaromatase drug in women with progressive metastatic breast cancer, and the characteristics of the patients more likely to respond, taking into account prior systemic treatment, should be defined by future studies.
Risks and Benefits of Aromatase Inhibitors in Postmenopausal Breast Cancer
TLDR
The clinical future of the selective aromatase inhibitors is promising, and these agents may change the way postmenopausal breast cancer is treated at all stages of the disease.
Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. Arimidex Study Group.
  • A. Buzdar, W. Jonat, P. Plourde
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 1996
TLDR
Anastrozole, 1 and 10 mg once daily, is well tolerated and as effective as megestrol acetate in the treatment of postmenopausal women with advanced breast cancer who progressed following tamoxifen treatment.
Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma
TLDR
This report presents the results of a survival update based on the combined data from two studies that compared the efficacy and tolerability of anastrozole (1 or 10 mg once daily) and megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma whose disease had progressed after treatment with tamoxifen.
Exemestane in advanced breast cancer
  • A. Buzdar
  • Biology, Medicine
    Anti-cancer drugs
  • 2000
TLDR
The most frequently reported drug-related adverse events are hot flushes, nausea and fatigue, which are consistent with the estrogen-suppressive effects of the drug.
Aromatase inhibitors in the treatment and prevention of breast cancer.
  • P. Goss, K. Strasser
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2001
TLDR
The ongoing adjuvant trials will provide important data on the long-term safety of aromatase inhibitors, which will help to determine their suitability for use as chemopreventives in healthy women at risk of developing breast cancer.
Phase I and endocrine study of exemestane (FCE 24304), a new aromatase inhibitor, in postmenopausal women.
TLDR
A single-dose administration of exemestane (FCE 24304; 6-methylenandrosta-1,4-diene-3,17-dione), a new irreversible aromatase inhibitor, was investigated in 29 healthy postmenopausal female volunteers and was found to be a well tolerated, potent, long-lasting, and specific inhibitor of estrogen biosynthesis.
ARIMIDEX™: A new oral, once-a-day aromatase inhibitor
Impact of tamoxifen on the pharmacokinetics and endocrine effects of the aromatase inhibitor letrozole in postmenopausal women with breast cancer.
  • M. Dowsett, C. Pfister, I. Smith
  • Biology, Medicine
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 1999
TLDR
It is possible that the antitumor efficacy of letrozole may be affected and sequential therapy may be preferable with these two drugs, and it is not known whether tamoxifen interacts with other members of this class of drugs or with other drugs in combination.
The efficacy of CGS 20267 in suppressing estrogen biosynthesis in patients with advanced stage breast cancer
...
1
2
3
4
5
...