Reduction of Side Effects From Aromatase Inhibitors Used for Treating Breast Cancer

Abstract

The present invention is directed generally to pharmaceutical compositions, methods, and kits for improving side effects associated with aromatase inhibitor treatment in a subject diagnosed with breast cancer. More specifically, the present invention provides compositions, methods, and kits comprising an aromatase inhibitor and an androgenic agent.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS[0001]This application claims the priority benefit of the following applications: 1) Australian Provisional Serial No. 2005905768, filed on Oct. 19, 2005, 2) U.S. Provisional Ser. No. 60 / 732,662, filed Nov. 3, 2005, and 3) U.S. Provisional Ser. No. 60 / 798,308, filed May 8, 2006. These applications, in their entirety, are incorporated herein by reference.FIELD OF THE INVENTION[0002]The present invention relates to the reduction of side effects caused by aromatase inhibitors which are used to treat subjects with breast cancer. In particular, the present invention provides compositions, methods, and kits for reducing side effects in post-menopausal women with breast cancer already being treated with aromatase inhibitor comprising administering an effective amount of an androgenic agent. Furthermore, the present invention provides compositions, methods, and kits for reducing side effects associated with aromatase inhibitor treatment in post-menopa...

AI Technical Summary

Benefits of technology

[0105]A method for measuring side effects associated with aromatase inhibitor treatment is within the scope of the present invention.

[0106]Both steroidal and non-steroidal aromatase inhibitors have shown clinical efficacy in the treatment of breast cancer. Recently, the American Society of Oncology has recommended that aromatase inhibitor be used as adjuvant therapy in all post-menopausal women with hormonally sensitive early breast cancer. This raises significant problems with the management of side-effects caused by total estrogen deprivation for periods of between five and ten years. Currently, the duration of hormonal adjuvant therapy is five years. However, this concept is being challenged, which may result in a longer duration of estrogen deprivation (Baum 2005). Most of the side-effects of aromatase inhibitors can be attributed to estrogen deprivation in specific tissues, but some are difficult to categorize. An example is loss of libido, which may have several synergistic etiologies, but appears to be significantly higher in Al than in TAM usage (Fallowfield, Cella et al 2004). However, there is little doubt that the musculoskeletal side-effects, such as arthralgia and osteoporosis, are a direct result of estrogen deprivation in these tissues and are a frequent occurrence in aromatase inhibitor users (Ingle 2005). Bone fractures during aromatase inhibitor therapy may be increased by as much as 60%, and this is probably a result of increased bone turnover (up by 20%), as well as accelerated bone loss (Eastell and Hannon 2005). The long-term side-effects of aromatase inhibitors are not known but are of concern, especially in the area of cognition (Jenkins, Shilling et al 2004), where estrogen is known to be especially important (reviewed in Sherwin 2003). There appears to be a critical window in the peri-menopausal period in which hormone levels may be critical to cognitive function (Sherwin 2003).

[0107]Administration of an androgenic agent simultaneously in combination with an aromatase inhibitor or following the administration of an aromatase inhibitor serves to improve one or more side effects associated with aromatase inhibitor administration, such as hot flush, hot flash, vasodilatation, osteoporosis, osteopenia, loss of libido, weight gain, vaginal dryness, sleeping difficulties, night sweats, asthenia, painful intercourse, pain, whole body pain, arthritis, arthralgia, breast pain, pharyngitis, depression, bloating, nausea, rash, mood swings, headache, diminished cognitive function, hypertension, insomnia, lymphoedema, back pain, peripheral edema, cold sweats, abdominal pain, injury, constipation, coughing, diarrhea, fracture, hypercholesteremia, dyslipidemia, infection, arthrosis, dizziness, dyspnea, paraesthesia, urinary tract infection, vulvovaginitis, anxiety, bone pain, chest pain, dyspepsia, flu syndrome, gastrointestinal disorder, sweating and/or leukorrhea. Preferably, administration of an androgenic agent simultaneously in combination with an aromatase inhibitor or following the administration of an aromatase inhibitor serves to improve one or more

Problems solved by technology

A more selective estrogen receptor regulator has so far not been successful in taking the place of tamoxifen and the current trend in hormonal therapy is to reduce the level of bio-available estrogen.

This drug was poorly tolerated and resulted in a marked adrenal suppression that limited the use of the drug.

A significant problem with these aromatase inhibitors, how

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