Aromasin, the unknown.

[IBdmfkr]

Lets compare and try and put together some legitimate info on this particular compound compared to similarly used AI's. This seems to be the one compound I have had the most trouble finding solid information on.

Small comparison I found on Cutting Edge, more to come, this is just the tip of the iceberg for this compound which is so often overlooked and much is unknown about IMO.
The best Anti A.
Arimidex : The most cheap (in my coutry, Brazil)
letrozole : Can increase de IGF-1(1), and have better in inhibiting aromatase activity (2)
Exemestane : A "irreversible aromatase inhibitor" (3) and because this dont make a negative feedback in the aromatase later the administration ?




#1

The aromatase inhibitor letrozole in advanced breast cancer: effects on serum insulin -like growth factor (IGF)-I and IGF-binding protein-3 levels.

Bajetta E, Ferrari L, Celio L, Mariani L, Miceli R, Di Leo A, Zilembo N, Buzzoni R, Spagnoli I, Martinetti A, Bichisao E, Seregni E.

Medical Oncology B Division, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.

Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels were measured in two groups of postmenopausal women with advanced breast cancer, who received the aromatase inhibitor letrozole 0.5 or 2.5 mg p.o. once daily. Blood samples were obtained from 15 patients in each dose group at baseline, and one and three months after starting therapy. Circulating IGF-I and IGFBP-3 concentrations were determined by means of radioimmunoassay. In both dosage groups a statistically significant increase in the IGF-I levels was observed during three months of letrozole treatment (P=0.003). In addition, the multiple testing procedure yielded in the whole patient population a significant result in the comparison between mean IGF-I values after three months of therapy and those observed at baseline (P=0.004), the estimated average increase being of 24%. No significant result was obtained in the analysis for the dose effect (P=0.077) and for the time x dose interaction (P=0.208). Circulating IGFBP-3 levels did not appear to be affected by letrozole treatment in either of the dose groups. This is the first report concerning the short-term effects of letrozole on components of the IGF system in breast cancer patients; further investigations are warranted in order to confirm these preliminary data.[/i]

#2

An open randomised trial of second-line endocrine therapy in advanced breast cancer. comparison of the aromatase inhibitors letrozole and anastrozole.


It was previously shown that letrozole (Femara) was significantly more potent than anastrozole (Arimidex) in inhibiting aromatase activity in vitro and in inhibiting total body aromatisation in patients with breast cancer. The objective of this study was to compare letrozole (2.5 mg per day) and anastrozole (1 mg per day) as endocrine therapy in postmenopausal women with advanced breast cancer previously treated with an anti-oestrogen. This randomised, multicentre and multinational open-label phase IIIb/IV study enrolled 713 patients. Treatment was for advanced breast cancer that had progressed either during anti-oestrogen therapy or within 12 months of completing that therapy. Patients had tumours that were either positive for oestrogen and/or progesterone receptors (48%) or of unknown receptor status (52%). The primary efficacy endpoint was time to progression (TTP). Secondary endpoints included objective response, duration of response, rate and duration of overall clinical benefit (responses and long-term stable disease), time to treatment failure, and overall survival, as well as general safety. There was no difference between the treatment arms in TTP; median times were the same for both treatments. letrozole was significantly superior to anastrozole in the overall response rate (ORR) (19.1% versus 12.3%, P=0.013), including in predefined subgroups (receptor status-unknown, and soft-tissue- and viscera-dominant site of disease). There were no significant differences between the treatment arms in the rate of clinical benefit, median duration of response, duration of clinical benefit, time to treatment failure or overall survival. Both agents were well tolerated and there were no significant differences in safety. These results support previous data documenting the greater aromatase-inhibiting activity of letrozole and indicate that advanced breast cancer is more responsive to letrozole than to anastrozole as second-line endocrine therapy.

Rose C, Vtoraya O, Pluzanska A, Davidson N, Gershanovich M, Thomas R, Johnson S, Caicedo JJ, Gervasio H, Manikhas G, Ben Ayed F, Burdette-Radoux S, Chaudri-Ross HA, Lang R.

Department of Oncology, Lund University Hospital, 221 85, Lund, Sweden. [email protected]

#3

Pharmacological and clinical profile of exemestane (Aromasin ), a novel irreversible aromatase inhibitor


Aromatase is the rate-limiting enzyme playing a role at the final step of estrogen biosynthesis, which is attracting attention as the target enzyme of hormone therapy of postmenopausal breast cancer. Exemestane (Aromasin) is a novel steroidal irreversible aromatase inhibitor that was approved in Japan as a therapeutic drug for postmenopausal breast cancer. Exemestane selectively inhibits aromatase activity in vitro, in a time-dependent and irreversible manner, suggesting the mechanism of action that exemestane covalently binds to aromatase as a pseudo-substrate and inactivates the enzyme. In vivo studies show the inhibitory effect of exemestane on the ovarian aromatase activity and plasma estradiol level of PMSG-primed rats. In studies using DMBA-induced rat mammary tumor models, exemestane shows antitumor activity in both conventional (premenopausal) and ovariectomized, testosterone -treated postmenopausal models. Despite its steroidal structure, exemestane does not have hormonal or anti-hormonal activity, except for a slight androgenic activity. In the early and late phase II clinical trials conducted in Japan on postmenopausal breast cancer patients who received 25 mg/day of exemestane, the response rates were 31.4% and 24.2%, respectively. Blood estrogen levels were also markedly reduced. These results confirmed the clinical relevance of non-clinical study results, as well as the possibility of extrapolation to foreign trial data.

Portfolio Management, Worldwide Safety Sciences, Pfizer Global Research and Development Nagoya Laboratories, Aichi, Japan. [email protected]

Tahara M, Nomura S, Hashimoto M.

[IBdmfkr]

bump^^^ hmmm....

[Myka]

You might try pming lion about it...he said very little in this post...

Question for Lion

[IBdmfkr]

I'd like to know how he came to that conclusion. Wonder if he has even run it or if he "really" means it is more expensive for HIM and would rather sell letro because there is greater profit. lol If I'm wrong Lion, please fill me in why you claim letro is far superior.