Delving into the Latest Updates on Atamestane with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [3]

Target

aromatase

Mechanism

aromatase inhibitors(Aromatase inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesUrogenital Diseases

Active Indication-

Inactive Indication

Advanced breast cancerBreast CancerMetastatic breast cancer+ [1]

Originator Organization

Bayer AG

Active Organization-

Inactive Organization

Intarcia Therapeutics, Inc.Bayer Schering Pharma AG

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC20H26O2

InChIKeyPEPMWUSGRKINHX-TXTPUJOMSA-N

CAS Registry96301-34-7

Protocol 777-CLP-32 is the treatment and survival continuation protocol of Biomed 777-CLP-29, and will continue to compare combined hormonal therapy using the experimental aromatase inhibitor (AI) atamestane combined with the FDA-approved anti-estrogen toremifene (Fareston®), to the single agent FDA-approved aromatase inhibitor letrozole (Femara®) for the treatment of advanced breast cancer. The purpose of this study is to determine whether maximal estrogen suppression achieved via the combination of atamestane, plus toremifene (Fareston®), is more effective than letrozole (Femara®) in delaying the growth of breast cancer.

Start Date01 Nov 2005

Sponsor / Collaborator

Intarcia Therapeutics, Inc.

NCT00097344

/ TerminatedPhase 3

Phase 3 Study of Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer

The purpose of this study is to determine whether maximal estrogen suppression achieved via the combination of an experimental drug, atamestane, plus an FDA-approved drug, toremifene (Fareston®), is more effective than another approved drug, letrozole (Femara®), in delaying the growth of breast cancer, and whether the side effects of the combined hormonal therapy are different from the side effects of letrozole.

Start Date01 Dec 2004

Sponsor / Collaborator

Intarcia Therapeutics, Inc.

NCT00044291

/ CompletedPhase 3

Phase III Study of Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer

The purpose of this study is to determine whether the first line combination hormonal therapy of an experimental drug, atamestane, plus an FDA-approved drug, toremifene (Fareston®), is more effective than another approved drug, letrozole (Femara®), in delaying the growth of breast cancer in postmenopausal patients with locally advanced or metastatic breast cancer, and whether the side effects of the combination are different from the side effects of letrozole.

Start Date01 Jun 2002

Sponsor / Collaborator

Intarcia Therapeutics, Inc.

100 Clinical Results associated with Atamestane

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100 Translational Medicine associated with Atamestane

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100 Patents (Medical) associated with Atamestane

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33

Literatures (Medical) associated with Atamestane

01 Feb 2009·The Journal of Steroid Biochemistry and Molecular BiologyQ2 · BIOLOGY

Comparing the effects of atamestane, toremifene and tamoxifen alone and in combination, on bone, serum lipids and uterus in ovariectomized rats

Q2 · BIOLOGY

Article

Author: Haiqing Hu ; Paul E. Goss ; Shangle Qi

Complete estrogen blockade remains under investigation as a means to optimize anti-estrogen therapy in breast cancer thus both the efficacy and end-organ toxicities are of interest with combinations. We hypothesized that a steroidal aromatase inhibitor (AI) atamestane (ATA) alone, and in combination with the anti-estrogens tamoxifen (TAM) or toremifene (TOR) would have beneficial effects in ovariectomized (OVX) rats on key end-organ functions including bone and lipid metabolism and on the endometrium. Significant positive effects on bone were noted with ATA, TOR, TAM, ATA+TOR, or ATA+TAM. TOR, TAM, ATA+TOR, or ATA+TAM caused significant decreases in serum cholesterol and low-density lipoprotein cholesterol whereas ATA had no effect. Uterine weight and epithelium lining height were not increased by ATA but were by TOR and TAM. No significant differences were found in the key parameters outlined above between OVX rats given TOR and ATA+TOR, or TAM and ATA+TAM. Our data show that ATA in combination with TOR or TAM is equivalent to TOR or TAM alone in terms of end-organ effects within a range of clinically relevant doses. Further studies of combinations of AIs with anti-estrogens on end-organ function are merited.

01 Jan 2008·The Journal of Steroid Biochemistry and Molecular BiologyQ2 · BIOLOGY

Toremifene–atamestane; alone or in combination: Predictions from the preclinical intratumoral aromatase model

Q2 · BIOLOGY

Article

Author: Yue Zhu ; Angela Brodie ; Gauri J. Sabnis ; Adam Schayowitz ; Olga Goloubeva ; Luciana Macedo

Since most breast cancers occur in postmenopausal women and are hormone dependent, we developed a model system that mimics this situation. In this model, tumors of human estrogen receptor (ER) positive breast cancer cells stably transfected with aromatase (Ac-1) are grown in immune-compromised mice. Using this model we have explored a number of therapeutic strategies to maximize the antitumor efficacy of antiestrogens (AEs) and aromatase inhibitors (AIs). This intratumoral aromatase xenograft model has proved accurate in predicting the outcome of several clinical trials. In this current study we compared the effect of an AE toremifene and steroidal AI atamestane, alone or in combination, on growth of hormone-dependent human breast cancer. We have also compared toremifene plus atamestane combination with tamoxifen in this study. The growth of Ac-1 cells was inhibited by tamoxifen, toremifene and atamestane in vitro with IC(50) values of 1.8+/-1.3 microM, 1+/-0.3 microM and 60.4+/-17.2 microM, respectively. The combination of toremifene plus atamestane was found to be better than toremifene or atamestane alone in vitro. The effect of this combination was then studied in vivo using Ac-1 xenografts grown in ovariectomized female SCID mice. The mice were injected with toremifene (1000 microg/day), atamestane (1000 microg/day), tamoxifen (100 microg/day), or the combination of toremifene plus atamestane. In this study, our results indicate that the combination of toremifene plus atamestane was as effective as toremifene or tamoxifen alone but may not provide any additional benefit over toremifene alone or tamoxifen alone.

01 Nov 2007·Journal of Clinical OncologyQ1 · MEDICINE

Phase III, Double-Blind, Controlled Trial of Atamestane Plus Toremifene Compared With Letrozole in Postmenopausal Women With Advanced Receptor-Positive Breast Cancer

Q1 · MEDICINE

Article

Author: Goss, Paul ; Manikhas, Georgiy N. ; Miller, Wilson H. ; Bondarenko, Igor N. ; Blanchett, Dennis ; Pendergrass, Kelly B. ; Langecker, Peter

Purpose To compare time to progression (TTP) with a steroidal aromatase inhibitor (AI) atamestane (ATA) combined with toremifene (TOR; complete estrogen blockade) versus letrozole (LET) in receptor-positive advanced breast cancer (ABC). Patients and Methods Eligibility included postmenopausal receptor-positive ABC and adjuvant hormonal therapy completed more than 12 months prior to study entry. Participants received daily ATA 500 mg with TOR 60 mg (ATA + TOR), or letrozole 2.5 mg (LET). The primary end point was TTP, whereas secondary objectives included objective response (OR), overall survival (OS), and time to treatment failure (TTF). The study had 80% power to detect a 25% increase in TTP assuming a TTP of 9.4 months in the LET population. Results A total of 865 patients were randomly assigned (434 to ATA + TOR and 431 to LET) in 60 centers in the United States, Canada, Russia, and Ukraine. Baseline characteristics were balanced. Median TTP was identical in the two arms at 11.2 months (P < .92). Median TTF was similar at 9.24 months (ATA + TOR) versus 10.44 months (LET). The hazard ratios (LET/ATA + TOR) were 1.00 (95% CI, 0.92 to 1.08) for TTP, 0.99 (95% CI, 0.92 to 1.06) for TTF, and 0.98 (95% CI, 0.87 to 1.11) for OS. OR occurred in 30% of patients receiving ATA + TOR and in 36% of patients receiving LET (P < .1). Adverse events (AEs) were similar for patients receiving ATA + TOR versus LET, and serious AEs were 10% v 11%, respectively. Conclusion TTP for patients receiving ATA + TOR was identical to that for patients receiving LET, representing the first endocrine therapy comparable to LET in ABC. Unlike in the Anastrozole, Tamoxifen, and Combined trial, addition of an antiestrogen did not decrease efficacy of the AI. Future studies of AIs in combination with more effective selective estrogen receptor modulators or selective receptor downregulators is warranted.

100 Deals associated with Atamestane

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Atamestane	-	DB12194

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced breast cancer	Phase 3	CA	Intarcia Therapeutics, Inc.	01 Jun 2002
Advanced breast cancer	Phase 3	RU	Intarcia Therapeutics, Inc.	01 Jun 2002
Advanced breast cancer	Phase 3	UA	Intarcia Therapeutics, Inc.	01 Jun 2002
Advanced breast cancer	Phase 3	US	Intarcia Therapeutics, Inc.	01 Jun 2002
Metastatic breast cancer	Phase 3	US	Intarcia Therapeutics, Inc.	01 Oct 2000
Breast Cancer	Phase 3	DE	Bayer Schering Pharma AG	01 Jan 1999
Prostatic Hyperplasia	Phase 3	-	Bayer Schering Pharma AG	01 Nov 1996

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2006	Phase 3	Advanced breast cancer First line	865	Atamestane 500 mg per day + Toremifene 60 mg per day	vonhrisavw(ghnwpybgss) = syittohwjv rolewttlei (akkbeoixsx )	-	20 Jun 2006
				Letrozole 2.5 mg per day	vonhrisavw(ghnwpybgss) = qdijwqwiux rolewttlei (akkbeoixsx )