Differences between the non-steroidal aromatase inhibitors anastrozole and letrozole – of clinical importance?

Aromatase inhibition is the gold standard for treatment of early and advanced breast cancer in postmenopausal women suffering from an estrogen receptor-positive disease. The currently established group of anti-aromatase compounds comprises two reversible aromatase inhibitors (anastrozole and letrozole) and on the other hand, the irreversible aromatase inactivator exemestane. Although exemestane is the only widely used aromatase inactivator at this stage, physicians very often have to choose between either anastrozole or letrozole in general practice. These third-generation aromatase inhibitors (letrozole/Femara (Novartis Pharmaceuticals, Basel, Switzerland) and anastrozole/Arimidex (AstraZeneca, Pharmaceuticals, Macclesfield, Cheshire, UK)), have recently demonstrated superior efficacy compared with tamoxifen as initial therapy for early breast cancer improving disease-free survival. However, although anastrozole and letrozole belong to the same pharmacological class of agents (triazoles), an increasing body of evidence suggests that these aromatase inhibitors are not equipotent when given in the clinically established doses. Preclinical and clinical evidence indicates distinct pharmacological profiles. Thus, this review focuses on the differences between the non-steroidal aromatase inhibitors allowing physicians to choose between these compounds based on scientific evidence. Although we are waiting for the important results of a still ongoing head-to-head comparison in patients with early breast cancer at high risk for relapse (Femara Anastrozole Clinical Evaluation trial; ‘FACE-trial'), clinicians have to make their choices today. On the basis of available evidence summarised here and until FACE-data become available, letrozole seems to be the best choice for the majority of breast cancer patients whenever a non-steroidal aromatase inhibitor has to be chosen in a clinical setting. The background for this recommendation is discussed in the following chapters

The patient experience

The impact of improved treatments for the management of hormone-sensitive breast cancer extends beyond clinical responses. Thanks to appropriate literature and access to the internet, patient awareness of treatment options has grown and patients are now, in many cases, able to engage their oncologists in informed conversations regarding treatment and what to expect in terms of efficacy and safety. Indeed, patients realize that although there is no cure for metastatic disease, treatment can greatly reduce the risk of progression and in the adjuvant setting, where treatment is administered with a curative intent, current treatment options reduce the risk of relapse. The approval of letrozole throughout the breast cancer continuum has provided patients with many reassuring options. The improvement in outcome with letrozole is achieved without a detrimental effect on overall quality of life. Adverse events such as hot flushes, arthralgia, vaginal dryness, and potential osteoporosis are most significant from the patient’s perspective, and it is important that caregivers pay attention to patients experiencing these events, as they can impact compliance unless effectively explained and managed. The major benefits of letrozole are to improve prospects for long-term survivorship in the adjuvant setting and to delay progression and the need for chemotherapy in the metastatic setting

Sorbents for High Temperature Removal of Arsenic from Coal-Derived Synthesis Gas

Gasification technologies convert coal and other heavy feedstocks into synthesis gas feed streams that can be used in the production of a wide variety of chemicals, ranging from hydrogen through methanol, ammonia, acetic anhydride, dimethyl ether (DME), methyl tertiary butyl ether (MTBE), high molecular weight liquid hydrocarbons and waxes. Syngas can also be burned directly as a fuel in advanced power cycles to generate electricity with very high efficiency. However, the coal-derived synthesis gas contains a myriad of trace contaminants that may poison the catalysts that are used in the downstream manufacturing processes and may also be regulated in power plant emissions. Particularly, the catalysts used in the conversion of synthesis gas to methanol and other liquid fuels (Fischer-Tropsch liquids) have been found to be very sensitive to the low levels of poisons, especially arsenic, that are present in the synthesis gas from coal. TDA Research, Inc. (TDA) is developing an expendable high capacity, low-cost chemical absorbent to remove arsenic from coal-derived syngas. Unlike most of the commercially available sorbents that physically adsorb arsenic, TDA's sorbent operates at elevated temperatures and removes the arsenic through chemical reaction. The arsenic content in the coal gas stream is reduced to ppb levels with the sorbent by capturing and stabilizing the arsenic gas (As4) and arsenic hydrides (referred to as arsine, AsH3) in the solid state. To demonstrate the concept of high temperature arsenic removal from coal-derived syngas, we carried out bench-scale experiments to test the absorption capacity of a variety of sorbent formulations under representative conditions. Using on-line analysis techniques, we monitored the pre- and post-breakthrough arsine concentrations over different sorbent samples. Some of these samples exhibited pre-breakthrough arsine absorption capacity over 40% wt. (capacity is defined as lb of arsenic absorbed/lb of sorbent), while maintaining an arsine outlet concentration at less than 10 ppb