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Breast Cancer


weeks with concomitant quinapril being started four weeks after anastrozole. A pharmacokinetic study of the plasma concentration of anastrozole was performed on days 21, 28, 42, 56 and 70. The plasma anastrozole levels were compared between the two groups and showed no significant difference. In addition, hypertension was well controlled in all patients. There was no evidence of clinically significant drug–drug interaction between anastrozole and quinapril.34


In 2006, Carlini et al. reported a case of liver toxicity after treatment with gefitinib and anastrozole in a 63-year-old woman.35


The study


hypothesised the possibility of drug–drug interactions through CYP450, but concluded that this interaction was unlikely as the pharmacokinetics of gefitinib are not altered by CYP3A4 inhibitors.36


In addition, this case report pointed out that in 2005 Polychronis et al. published a


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7. Coombes RC, Hall E, Gibson LJ, et al., A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer, N Engl J Med, 2004;350:1081–92.


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10. Boccardo F, Rubagotti A, Puntoni M, et al., Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: preliminary results of the Italian Tamoxifen Anastrozole Trial, J Clin Oncol, 2005;23:5138–47.


11. Winer EP, Hudis C, Burstein HJ, et al., American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004, J Clin Oncol, 2005;23:619–29.


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randomised controlled trial comparing preoperative gefitinib versus gefitinib and anastrozole in treating 56 post-menopausal patients with oestrogen-receptor-positive, epidermal growth factor-receptor-positive breast cancer. Polychronis et al. reported that there was no effect of anastrozole on the pharmacokinetics of gefitinib, although data were not shown.37


Conclusion


Anastrozole is a potent non-steroidal AI that selectively inhibits aromatase. It is the first AI approved by the FDA as an adjuvant hormonal therapy in early-stage breast cancer. The standard dose of anastrozole is 1mg/day orally. There have been no significant drug–drug interactions between anastrozole and other drugs reported to date. n


with aminoglutethimide: clinical studies in postmenopausal patients with metastatic breast carcinoma, Ann Surg, 1978;187:475–84.


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19. Baum M, Budzar AU, Cuzick J, et al., ATAC Trialists’ Group, Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial, Lancet, 2002;359:2131–9.


20. Baum M, Buzdar A, Cuzick J, et al., Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early- stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses, Cancer, 2003;98:1802–10.


21. Center AN, Drug To Prevent Breast Cancer Recurrence Gets FDA Approval, 2002. Available at: www.cancer.org/docroot/ NWS/content/NWS_1_1x_New_Drugs_Or_Old_Standard_ Better_For_Breast_Cancer.asp


22. Lønning PE, Geisler J, Dowsett M, Pharmacological and clinical profile of anastrozole, Breast Cancer Res Treat, 1998;49(Suppl. 1):S53–7, discussion S73–7.


23. Yates RA, Dowsett M, Fisher GV, et al., Arimidex (ZD1033): a selective, potent inhibitor of aromatase in postmenopausal female volunteers, Br J Cancer, 1996;73:543–8.


24. Jonat W, Howell A, Blomqvist C, et al., A randomised trial comparing two doses of the new selective aromatase inhibitor anastrozole (Arimidex) with megestrol acetate in


postmenopausal patients with advanced breast cancer, Eur J Cancer, 1996;32A:404–12.


25. Buzdar AU, Jones SE, Vogel CL, et al., A phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma. Arimidex Study Group, Cancer, 1997;79:730–9.


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29. Geisler J, King N, Dowsett M, et al., Influence of anastrozole (Arimidex), a selective, non-steroidal aromatase inhibitor, on in vivo aromatisation and plasma oestrogen levels in postmenopausal women with breast cancer, Br J Cancer, 1996;74:1286–91.


30. Grimm SW, Dyroff MC, Inhibition of human drug metabolizing cytochromes P450 by anastrozole, a potent and selective inhibitor of aromatase, Drug Metab Dispos, 1997;25:598–602.


31. Dowsett M, Cuzick J, Howell A, et al., Pharmacokinetics of anastrozole and tamoxifen alone, and in combination, during adjuvant endocrine therapy for early breast cancer in postmenopausal women: a sub-protocol of the ‘Arimidex and tamoxifen alone or in combination’ (ATAC) trial, Br J Cancer, 2001;85:317–24.


32. Bao T, Slater SA, Blackford B, et al., Effect of simvastatin on the pharmacokinetics of anastrozole, J Clin Oncol, 2009;27:15s, abstract 1517.


33. Yates RA, Wong J, Seiberling M, et al., The effect of anastrozole on the single-dose pharmacokinetics and anticoagulant activity of warfarin in healthy volunteers, Br J Clin Pharmacol, 2001;51:429–35.


34. Repetto L, Vannozzi O, Hazini A, et al., Anastrozole and quinapril can be safely coadministered to elderly women with breast cancer and hypertension: a pharmacokinetic study, Ann Oncol, 2003;14:1587–8.


35. Carlini P, Papaldo P, Fabi A, et al., Liver toxicity after treatment with gefitinib and anastrozole: drug-drug interactions through cytochrome p450?, J Clin Oncol, 2006;24:e60–1.


36. Swaisland HC, Ranson M, Smith RP, et al., Pharmacokinetic drug interactions of gefitinib with rifampicin, itraconazole and metoprolol, Clin Pharmacokinet, 2005;44:1067–81.


37. Polychronis A, Sinnett HD, Hadjiminas D, et al., Preoperative gefitinib versus gefitinib and anastrozole in postmenopausal patients with oestrogen-receptor positive and epidermal- growth-factor-receptor-positive primary breast cancer: a double-blind placebo-controlled phase II randomised trial, Lancet Oncol, 2005;6:383–91.


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EUROPEAN ONCOLOGY & HAEMATOLOGY


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