4- Letrozole

Like anastrozole, letrozole is a third generation, type II nonsteroidal aromatase inhibitor. Renal excretion of its... 

Itoh T, Karlsberg K, Kijima I, Yuan YC, Smith D, Ye J, et al. Letrozole-, anas-trozole-, and tamoxifen-responsive genes in MCF-7aro cells a microarray approach. Mol Cancer Res 2005 3 203-18. 

Chronic renal disease Aromatase inhibitors (anastrazole, exemestane, letrozole)... 

Letrozole is another selective aromatase that inhibits the conversion of androgens to estrogen. Maximum plasma concentrations occur 1 hour after oral dosing concomitant food has not been shown to have an effect on the extent of absorption of letrazole. The terminal half-life is approximately 2 days. Letrozole is used in the treatment of postmenopausal women with hormone-receptor-positive or unknown advanced breast cancer. Side effects include bone pain, hot flushes, back pain, nausea, arthralgia, osteoporosis/bone fractures, and dyspnea. 

Successful coadministration of bisphosphonates with the aro-matase inhibitors has been accomplished in many patients in the metastatic setting. The three available aromatase inhibitors are exemestane, anastrozole, and letrozole. 

Nonsteroidal Steroidal Anastrozole Letrozole Exemestane 1 mg orally daily 2.5 mg orally daily 25 mg orally daily Hot flashes, arthralgias, myalgias, headaches, diarrhea, mild nausea, osteoporosis (boneloss)... 

Letrozole 2.5 mg once daily 15% Headache, nausea, dyspepsia, skin rash 1. No protective effect on bone recommend calcium supplementation. 

Options for adjuvant hormonal therapy in postmenopausal women include aromatase inhibitors (e.g. anastrozole, letrozole, or exemestane) either in place of or after tamoxifen. Adverse effects with aromatase inhibitors include hot flashes, myalgia/arthralgia, vaginal dryness/atrophy, mild headaches, and diarrhea. 

Kilic-Okman T, Kucuk M, Altaner S (2003) Comparison of the effects of letrozole and clomiphene citrate on ovarian follicles, endometrium, and hormone levels in the rat. FertilSteril 80 1330-1332... 

The liquid chromatograph Zarghi et al. used consisted of a Wellchrom K-1001 pump, Rheodyne 7125 injector, Eurochrom 2000 integrator, and K2600 fluorescence detector. The stationary phase was a Merck Chromolith Performance RP-18e column (100 x 4.6 mm). The mobile phase consisted of 0.01M dibasic sodium phosphate buffer and acetonitrile (60 40 v/v) adjusted to pH 3.5. The flow rate was 2 mL/min. The detector operated at an excitation wavelength of 240 nm and an emission wavelength of 340 nm. Letrozole served as the internal standard (IS). 

Stock solutions of carvedilol (8 mg/mL) and letrozole (10 mg/mL) were prepared in methanol and stored at 4°C. Standard solutions were prepared by spiking blank plasma with stock solutions. Aliquots (450, uL) of standard solutions and patient plasma samples were mixed with 50 fiL of the IS (10 jUg/mL) followed by 500 fiL of acetonitrile, vortexed for 30 sec, and centrifuged at 8000 g for 10 min. Supernatants were collected and assayed. The injection volume was 20 fiL. Figure 11.1 illustrates typical chromatograms of carvedilol and letrozole in plasma. 

FIGURE 11.1 Chromatograms of (A) blank plasma (B) blank plasma spiked with 60 ng/mL carvedilol and 1000 ng/mL letrozole (internal standard) and (C) plasma sample from a healthy volunteer 2 hr after oral administration of 25 mg of carvedilol. (Source From Zarghi, A. et al. J Pharm Biomed Anal. 44, 252, 2007. With permission.)... 

Aromatase inhibitors (including anastrozole, letrozole, aminoglutethimide, exemestane, formestane, testolactone), selective estrogen receptor modulators—SERMs (including raloxifene, tamoxifen, toremifene), clomiphene, cyclofenil, fulvestrant Diuretics, amiloride, bumetanide, canrenone, chlorthalidone, etacrynic acid, furosemide, indapamide, metolazone, spironolactone, thiazides, triamterene... 

Currently, anastrozole and letrozole are efficacious in early-stage, locally advanced, and mefasfafic disease and fhus they present with the most complete data set for the different stages of breast cancer. Although it seems rather unlikely that one will be able to detect differences with respect to clinical effects at the tumour level, the indirect comparison of different AIs suggests a stronger evidence for the use of exemestane compared with other AIs for breast cancer therapy [90]. 

Imatinib (Gleevec) Irinotecan (Camptosar) Lapatinib (Tykerb) Letrozole (Femara) Leucovorin (Wellcovorin) Mitoxantrone (Novantrone) Paclitaxel (Taxol, Abraxane)... 

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