|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
© 2001 American Society for Clinical Oncology
Aromatase Inhibitors and Arthralgia
Guy’s HospitalLondon, United Kingdom To the Editor:In their excellent review, Goss and Strasser1 summarize data supporting the current use of aromatase inhibitors (AIs) as second-line hormone treatment of postmenopausal women with estrogen receptor–positive metastatic breast cancer (MBC). They also examine the rationale for considering these agents in the first-line metastatic, adjuvant, neoadjuvant, and chemopreventive settings, particularly in view of their "significantly superior toxicity profiles." Although anastrozole, the first third-generation AI to be licensed for treatment of MBC, is generally well-tolerated, we are concerned that one particular side effect, namely arthralgia, is being overlooked. At our center over the last 4 years, we treated 77 estrogen receptor–positive MBC patients with anastrozole 1 mg daily. All 77 patients were postmenopausal women (median age, 64 years) who had failed tamoxifen therapy. None had previous arthritis or symptoms of arthralgia associated with menopause, prior chemotherapy, or hormone therapy. Within 2 months of starting anastrozole, 12 (16%) of 77 MBC patients complained of joint pains. The arthralgia was mostly grades 1/2, but four patients (5%) had to discontinue anastrozole because of severe arthralgia. In decreasing order, the areas most commonly affected were hands, knees, hips, lower back, and shoulders. Early morning stiffness was a common feature. Discontinuation of anastrozole led to resolution of symptoms. Patients were not rechallenged with anastrozole. Randomized trials of anastrozole, as first- and second-line hormone treatment of MBC, have not listed arthralgia as a significant toxicity. We note, however, that arthralgia has been reported in 13% of patients treated with two other third-generation AIs, letrozole2 and vorozole.3 Discussions with the manufacturers of anastrozole in the United Kingdom prompted a reanalysis of toxicities reported in the anastrozole studies. In the earlier, second-line study,4 arthralgia was reported by 5% of patients treated with anastrozole versus 4% of those treated with megestrol acetate (P = .431). In the more recent and larger first-line studies,5,6 arthralgia was reported by 10.5% of patients treated with anastrozole versus 5.7% of those treated with tamoxifen (P = .005). The incidence of arthralgia associated with anastrozole in the latter studies (10.5%) is similar to that reported in the other third-generation AI studies (13%) and our own study (16%). These data were presented by one of us (P.P.D.) at the Nottingham Breast Cancer Conference 1999. We conclude that arthralgia occurs in 10% to 15% of patients treated with an AI and that this is a class-effect, regardless of type of third-generation AI used. The cause of the arthralgia is not clear. There is some evidence in the literature of an association between menopausal status, low estrogen levels, and joint pains.7 Whereas tamoxifen, ovarian ablation, and second generation AI’s reduce estrogen effects to some degree, only third-generation AIs reduce circulating estrogens to undetectable levels. We postulate that this precipitous fall in estrogen levels is the cause of the observed arthralgia. REFERENCES
1.
Goss PE, Strasser K: Aromatase inhibitors in the treatment and prevention of breast cancer. J Clin Oncol 19: 881-894, 2001 2. Dombernowsky P, Smith I, Falkson G, et al: Letrozole, a new oral aromatase inhibitor for advanced breast cancer: Double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate. J Clin Oncol 16: 453-461, 1998[Abstract]
3.
Goss PE, Winer EP, Tannock IF, et al: Randomized phase III trial comparing the new potent and selective third-generation aromatase inhibitor vorozole with megestrol acetate in postmenopausal advanced breast cancer patients: North American Vorozole Study Group. J Clin Oncol 17: 52-63, 1999 4. Buzdar AU, Jonat W, Howell A, et al: Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: Results of a survival update based on a combined analysis of data from two mature phase III trials—Arimidex Study Group. Cancer 83: 1142-1152, 1998[Medline]
5.
Bonneterre J, Thurlimann B, Robertson JF, et al: Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: Results of the tamoxifen or arimidex randomized group efficacy and tolerability study. J Clin Oncol 18: 3748-3757, 2000
6.
Nabholtz JM, Buzdar A, Pollak M, et al: Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: Results of a north american multicenter randomized trial. J Clin Oncol 18: 3758-3767, 2000 7. Pansini F, Albertazzi P, Bonaccorsi G, et al: The menopausal transition: A dynamic approach to the pathogenesis of neurovegetative complaints. Eur J Obstet Gynecol Reprod Biol 57: 103-109, 1994[Medline] This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2001 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
