Evidence-based medicine: comparative analysis of luteinizing hormone-releasing hormone analogues in combination with external beam radiation and surgery in the treatment of carcinoma of the prostate.

UNLABELLED: What's known on the subject? and What does the study add? Luteinizing hormone-releasing hormone analogues are a cornerstone in the management of many clinical situations in prostate cancer patients. The multiplicity of drugs make it difficult to decide which is the best drug to prescribe to each patient. Whether or not the different luteinizing hormone-releasing hormone analogues belong to the same drug class is only merely supposed. This study adds a systematic review of the literature in order to determine whether or not the luteinizing hormone-releasing hormone analogues available for prescription belong to the same drug class (same family, similar chemical structure, mechanism of action, and efficacy). The current evidence available is not enough to support a presumed drug class effect of the various analogues in the treatment of prostate carcinoma. OBJECTIVE: • To study whether luteinizing hormone-releasing hormone (LHRH) analogues are agents of the same pharmacological class, i.e. whether they have the same clinical effect, using an evidence-based medicine approach. MATERIAL AND METHODS: • We reviewed the evidence on the alleged 'drug class effect' among analogues and the existing bibliographic support for their use in various medical indications. We used PubMed as the main search source. Evidence level and degree of recommendation were assigned to each conclusion based on the 'Scottish Intercollegiate Guidelines Network'. RESULTS: • There are no studies designed to answer the question of class effect between LHRH analogues or agonists. Reviews and meta-analyses have been performed on many other issues related to therapeutic management either with analogues alone, or in combination with radiation therapy and surgery. • Direct comparisons do not allow definitive conclusions to be reached. Indirect evidence is obtained from randomized studies comparing the different LHRH analogues with other treatments used to obtain androgen deprivation. Other issues related to pharmacokinetics and pharmacodynamics that can support either the existence or non-existence of class effect were evaluated. CONCLUSION: • The current available evidence is not enough to support a presumed class effect of the drug among the different analogues in the treatment of prostate carcinoma in its various clinical situations.

The similarities of aromatase inhibitors outweigh the differences.

Although the aromatase inhibitors (AIs) as a class exhibit clear differences in terms of their structure and mechanism of action, these differences do not always translate into clinically significant differences in patient outcomes. In fact, these differences may actually reflect differences in clinical trial design (i.e. upfront, sequential or switch therapy) or the patient population studied. The results of clinical trials demonstrate a clear superiority of third-generation AIs over tamoxifen. It will, however, be necessary to wait for the results of the ongoing head-to-head MA.27 and Novartis trials to determine whether there is any differentiation between the various third-generation AIs.

Hormonal breast cancer agents: implications for the primary care provider.

PURPOSE: Over 2 million breast cancer survivors are in the United States, making women with breast cancer the largest group of cancer survivors. The purpose of this article is to review the current knowledge regarding survivorship issues in women with early-stage, estrogen receptor-positive breast cancer, focusing on advances in hormonal therapies for reducing risk of recurrence. DATA SOURCES: Published research studies, clinical treatment guidelines, and ongoing clinical trials. CONCLUSIONS: Innovations in antiestrogenic and estrogen modulator therapies are an important aspect of ongoing care after primary breast cancer treatment. Primary care providers may play an important role in monitoring potential complications of antiestrogenic treatment. IMPLICATIONS FOR PRACTICE: This article reviews the current state of the science in hormonal breast cancer agents for breast cancer survivors. With the high incidence and prevalence of breast cancer, primary care providers need to be aware of the potential short- and long-term health risks and benefits of hormonal therapies for breast cancer survivors.

Comparative assessment of the inhibition of recombinant human CYP19 (aromatase) by azoles used in agriculture and as drugs for humans.

Azoles (imidazoles and triazoles) are used as antifungal agents in agriculture and in medicine, and also for antiestrogen therapy, e.g., for breast cancer treatment. Antifungal activity is based on inhibition of fungal CYP51 (lanosterol 14alpha-demethylase), and estrogen biosynthesis reduction is due to azole inhibition of CYP19 (aromatase). Inhibition of aromatase by antifungal agents is usually an unwanted side effect and may cause endocrine disruption. A fluorimetric assay based on human recombinant CYP19 enzyme with dibenzylfluorescein as a substrate was used to compare the inhibitory potency of 22 azole compounds. Dose responses were established and duplicate datasets were analyzed with a nonlinear mixed-effects model with cumulative normal distribution for the logarithm of concentration. IC50 values (50% inhibitory concentration) of 13 fungicides used in agriculture ranged more than 700-fold, starting from 0.047 microM. The potency of seven human drugs spanned more than 7000-fold, starting from 0.019 microM. Most potent fungicides included prochloraz, flusilazole, and imazalil, and most potent medicinal antifungals were bifonazole, miconazole, and clotrimazole. These in vitro data indicate that the top-ranking azoles used as antifungal agents or drugs are as potent inhibitors of aromatase as are antiestrogen therapeutics used to treat breast cancer. These putative effects of azole agents and drugs on steroid biosynthesis and sex hormone balance should be considered when used in human subjects and also in wildlife exposed to azole fungicides used in agriculture.

Aromatase inhibitors: current indications and future prospects for treatment of postmenopausal breast cancer.

This article provides a comprehensive review of aromatase inhibitors (AIs) for geriatricians, because it appears that more elderly women will be using these drugs in the near future. Computerized literature searches of Medline were conducted through May 2003. Key words/phrases included in the literature searches were aromatase inhibitors, estrogen, and breast cancer. Limits included English language, age 65 and older, and female sex. All relevant articles were selected and reviewed. AIs suppress intratumoral and plasma estrogen levels significantly. Third-generation AIs have excellent pharmacological profiles, with no significant drug interactions and better tolerability. These drugs have shown superiority compared with conventional therapies. The results of anastrozole, tamoxifen, and combination trials favors anastrozole over tamoxifen for adjuvant treatment, but further follow-up is required. AIs are approved for the treatment of advanced metastatic breast cancer (BC) in postmenopausal women whose disease has progressed during tamoxifen therapy. Recent trials have shown that the highly selective third-generation AIs are effective when used as first-line therapy in metastatic BC. Their possible use in preventive, adjuvant, and neoadjuvant settings is also being explored.

Advances in endocrine therapy for breast cancer: considering efficacy, safety, and quality of life.

Breast cancer is the most common cancer found in women in the United States. Endocrine therapy is the standard of care for most women with hormone receptor-positive tumors in adjuvant and metastatic settings. The selective estrogen response modifier tamoxifen has been the standard treatment for postmenopausal patients for many years. Numerous new endocrine therapy agents provide women with novel treatment options, including the nonsteroidal aromatase inhibitors anastrozole and letrozole, the steroidal aromatase inhibitor exemestane, and the estrogen receptor antagonist fulvestrant. Clinical trials have begun to define the role of these agents and their unique side-effect profiles. Nurses are vital in supporting patients in the decision-making process, managing side effects of treatment, and making observations to enhance understanding of the patient experience with new treatments. This article will assist nurses in educating patients about endocrine therapy options and their associated potential short- and long-term side effects, as well as treatment demands.

Mechanisms of action of endocrine treatment in breast cancer.

Endocrine treatment plays an important role in the therapy of breast cancer. While the basic mechanisms are understood, additional mechanisms may be of importance to their action and they may also contribute to the mechanism(s) of acquired resistance. Currently, several novel drugs are entering into clinical trials. Observations of the absence or presence of cross resistance to novel 'pure' steroidal antiestrogens and the non-steroidal tamoxifen may add important information to our understanding of the mechanisms of action of both classes of drugs. Similarly, exploration of different aromatase inhibitors in sequence or concert, as well as the combining of different endocrine treatment options may be warranted. Additionally, alterations in different biochemical parameters such as growth factors should not only be carefully explored in relation to treatment options but should also be followed during the course of treatment to asess alterations over time and in relation to the development of drug resistance.