Clomiphene citrate effect on testosterone level and semen parameters in 18 infertile men with low testosterone level and normal/low gonadotropines level.

OBJECTIVE: To determine the effect of a 3-month course of clomiphene citrate (CC) on plasma testosterone (T) level and on semen parameters in 18 infertile men with low T level and normal or low gonadotropines level. STUDY DESIGN: A retrospective study was conducted by reviewing the medical records of men referred to a university fertility medicine unit for infertility management between January 2010 and March 2015. Men treated with CC for at least 3 months were included if they presented with: RESULTS: 18 patients met the inclusion criteria. CC was prescribed for 3 months at the dose of 50 mg every 48 h. Plasma T level was assessed at baseline and after 1 month of CC administration. Semen parameters were assessed at baseline and after 3 months of CC administration. The median pre-treatment T level was 9.1 nmol/l; after 1 month of CC treatment the median post-treatment T level increased to 20.2 nmol/l (p = <0.001). Median baseline sperm concentration was 7 millions/ml with a median progressive motility of 18%. After 3 months of CC, the median post-treatment sperm concentration was 17.5 millions/ml (p = 0.024) and the median post-treatment progressive sperm motility was 18% (p = 0.40). Three natural pregnancies occurred during the treatment period. CONCLUSION: CC is an effective and inexpensive treatment to increase plasma T level in infertile men with low T level and normal or low gonadotropines level. Our study suggests that CC could increase sperm concentration even in oligospermic infertile men, without, however, a significant effect on progressive sperm motility. More powered randomized controlled trials are needed to definitively assess CC effect on sperm parameters and on natural pregnancy rates.

Social and ethical implications of BRCA testing.

Oncologists are asked with increasing frequency to counsel their patients with respect to the medical, psychological and social repercussions of genetic testing for cancer susceptibility that may have been prescribed by physicians or carried out through direct-to-consumer tests. This article critically reviews the main ethical and social implications of BRCA testing, focusing on genetic responsibility and genetic discrimination. Genetic responsibility toward oneself and others is a highly debated implication of genetic testing for cancer predisposition that requires broad considerations of the boundaries between individual and community rights and a reappraisal of the notion of autonomy as relational. Physicians' duty to warn 'at risk' relatives can be an ethical quandary, yet confidentiality is key to the patient-doctor relationship. Mutation carriers may be subject to different forms and degrees of genetic discrimination and many individuals at risk have forgone BRCA testing to avoid potential discrimination. The scientific and medical community, together with patients and the public, has actively engaged against genetic discrimination. The legislation in many countries now protects against genetic discrimination by insurance companies and employers. Legal and regulatory issues are not the final answer to discrimination and profound cultural changes are required to create understanding and acceptance of all differences.

The illness trajectory of elderly cancer patients across cultures: SIOG position paper.

BACKGROUND: Due to the aging of the population, cancer has become a health priority worldwide. While the number of elderly cancer patients is rapidly increasing, many barriers still exist to their effective management. Compared with their younger counterparts, the elderly are less likely to receive optimal medical, psychological and spiritual treatment provided in a culturally competent manner. DESIGN: The scanty literature on cultural competence in elderly cancer patients has been reviewed. Additional material has been selected based on the authors' clinical research in medical oncology and psycho-oncology, and on their scholarly work in anthropology and bioethics. RESULTS: The aging process is a synergistic product of biological, behavioral and social issues within a cultural context. Knowledge about how older people understand, perceive and experience their illness trajectory and make choices is essential to the planning and delivering of effective cancer care. CONCLUSION: This position paper of the SIOG Task Force on Cultural Competence in the Elderly creates awareness of the influence of culture in geriatric oncology. Negotiating cross-cultural issues in geriatric oncology helps managing possible conflicts between patients, families and physicians over differing health care values, beliefs, or practices. Possible areas of future scholarly investigation and clinical research are identified.

Cultural aspects of communication in cancer care.

Cancer is increasing in incidence and prevalence worldwide, and the WHO has recently included cancer and its treatments as a health priority in developed and developing countries. The cultural diversity of oncology patients is bound to increase, and cultural sensitivity and competence are now required of all oncology professionals. A culturally competent cancer care leads to improved therapeutic outcome and it may decrease disparities in medical care. Cultural competence in medicine is a complex multilayered accomplishment, requiring knowledge, skills and attitudes whose acquisition is needed for effective cross-cultural negotiation in the clinical setting. Effective cultural competence is based on knowledge of the notion of culture; on awareness of possible biases and prejudices related to stereotyping, racism, classism, sexism; on nurturing appreciation for differences in health care values; and on fostering the attitudes of humility, empathy, curiosity, respect, sensitivity and awareness. Cultural competence in healthcare relates to individual professionals, but also to organizations and systems. A culturally competent healthcare system must consider in their separateness and yet in there reciprocal influences social, racial and cultural factors. By providing a framework of reference to interpret the external world and relate to it, culture affects patients' perceptions of disease, disability and suffering; degrees and expressions of concern about them; their responses to treatments and their relationship to individual physicians and to the healthcare system. Culture also influences the interpretation of ethical norms and principles, and especially of individual autonomy, which can be perceived either as synonymous with freedom or with isolation depending on the cultural context. This, in turn, determines the variability of truth-telling attitudes and practices worldwide as well as the different roles of family in the information and decision-making process of the cancer patient. Finally, culture affects individual views of the patient-doctor relationship in different contexts.

Genetic medicine: the balance between science and morality.

This article explores the relationship between science and morality with respect to the major changes that genetic knowledge has induced in medicine, as well as in many other spheres of our lives. The following themes are treated: (i) the influence of genetic knowledge on the concepts of normalcy and diversity with respect to health; (ii) the influence of genetic knowledge on the concept of responsibility; (iii) the reciprocal influence of pre-existing biases and genetic knowledge; (iv) the influence of genetic knowledge on the concept of community; and (v) the influence of genetic knowledge on autonomy and trust in the patient-doctor relationship. The article does not wish to be prescriptive, but rather to raise open questions. The key philosophical question is to what extent human beings benefit from predictions about the future. The role attributed to genetics is largely overestimated. Genetic knowledge can be perceived as enhancing the control that individuals have on their lives, or as paralyzing the decision process of an individual who may feel predestined to a serious disease. In the case of breast and ovarian cancer, the probabilistic nature of genetics is especially relevant, given the relatively low penetrance of BRCA mutations. "Future things: not our domain. But in this today which unravels in front of us, what shall we do?" (Sophocles, Antigones).

Ethical implications of genetic testing for breast cancer susceptibility.

The identification of gene mutations involved in hereditary breast cancer is a major recent scientific discovery, enabling us to identify women at very high risk, and also providing the means to understand the biology of breast cancer and to explore novel preventive strategies. Yet, it carries medical, psychological, ethical and social implications. This paper is a review of all the ethical implications of genetic testing for breast cancer predisposition, as well as an attempt to discuss the more philosophical questions of women facing BRCA testing. To what extent does the individual benefit from genetic knowledge? Some women look with trepidation upon the potential of planning their life in view of a risk, while others believe that only through knowledge and awareness we can improve control of our life. The risk of breast cancer may be qualitatively so important to justify all the potential risks of finding out about it.

5-year results of dose-intensive sequential adjuvant chemotherapy for women with high-risk node-positive breast cancer: A phase II study.

PURPOSE: We conducted a phase II pilot study of dose-intensive adjuvant chemotherapy with doxorubicin followed sequentially by high-dose cyclophosphamide to determine the safety and feasibility of this dose-dense treatment and to estimate the disease-free and overall survival in breast cancer patients with four or more involved axillary lymph nodes. PATIENTS AND METHODS: Seventy-three patients received adjuvant treatment with four cycles of doxorubicin 75 mg/m(2) as an intravenous bolus every 21 days, followed by three cycles of cyclophosphamide 3,000 mg/m(2) every 14 days with granulocyte colony-stimulating factor support. RESULTS: Seventy-one patients were assessable, and all but two completed all planned chemotherapy. There was no treatment-related mortality. The most common toxicity was neutropenic fever, which occurred in 39% of patients. Median disease-free survival is 66 months (95% confidence interval, 34 to 98 months), and median overall survival has not yet been reached. At 5 years of follow-up, the disease-free survival is 51.7%, and overall survival is 60.0%. There is no long-term treatment-related toxicity, and no cases of acute myelogenous leukemia or myelodysplastic syndrome have been observed. CONCLUSION: Our pilot study of doxorubicin followed by cyclophosphamide demonstrates the safety and feasibility of the sequential dose-dense plan. Long-term follow-up, although noncomparative, is promising. However, this regimen is associated with a higher incidence of toxicity (and also higher costs) than the standard dose and schedule of doxorubicin and cyclophosphamide, and therefore it should not be used as conventional therapy in the absence of demonstrated improvement of outcome. Randomized trials testing the dose-dense approach have been completed but not yet reported. Because the sequential plan can decrease overlapping toxicities, it is an appropriate platform for the addition of newer active agents, such as taxanes or monoclonal antibodies.

Sequential dose-dense doxorubicin, paclitaxel, and cyclophosphamide for resectable high-risk breast cancer: feasibility and efficacy.

PURPOSE: Dose-dense chemotherapy is predicted to be a superior treatment plan. Therefore, we studied dose-dense doxorubicin, paclitaxel, and cyclophosphamide (A-->T-->C) as adjuvant therapy. METHODS: Patients with resected breast cancer involving four or more ipsilateral axillary lymph nodes were treated with nine cycles of chemotherapy, using 14-day intertreatment intervals. Doses were as follows: doxorubicin 90 mg/m2 x 3, then paclitaxel 250 mg/m2/24 hours x 3, and then cyclophosphamide 3.0 g/m2 x 3; all doses were given with subcutaneous injections of 5 microg/kg granulocyte colony-stimulating factor on days 3 through 10. Amenorrheic patients with hormone receptor-positive tumors received tamoxifen 20 mg/day for 5 years. Patients treated with breast conservation, those with 10 or more positive nodes, and those with tumors larger than 5 cm received radiotherapy. RESULTS: Between March 1993 and June 1994, we enrolled 42 patients. The median age was 46 years (range, 29 to 63 years), the median number of positive lymph nodes was eight (range, four to 25), and the median tumor size was 3.0 cm (range, 0 to 11.0 cm). The median intertreatment interval was 14 days (range, 13 to 36 days), and the median delivered dose-intensity exceeded 92% of the planned dose-intensity for all three drugs. Hospital admission was required for 29 patients (69%), and 28 patients (67%) required blood product transfusion. No treatment-related deaths or cardiac toxicities occurred. Doxorubicin was dose-reduced in four patients (10%) and paclitaxel was reduced in eight (20%). At a median follow-up from surgery of 48 months (range, 3 to 57 months), nine patients (19%) had relapsed, the actuarial disease-free survival rate was 78% (95% confidence interval, 66% to 92%), and four patients (10%) had died of metastatic disease. CONCLUSION: Dose-dense sequential adjuvant chemotherapy with doxorubicin, paclitaxel, and cyclophosphamide (A-->T-->C) is feasible and promising. Several ongoing phase III trials are evaluating this approach.

Phase I study of escalating doses of edatrexate in combination with paclitaxel in patients with metastatic breast cancer.

Motivated by the observation of preclinical synergy, a Phase I dose escalation study of edatrexate in combination with a 3-h paclitaxel infusion was performed in patients with advanced breast cancer to determine the maximum tolerated dose (MTD) of edatrexate and the toxicities associated with this combination and to report preliminary observations of efficacy with this novel combination. Thirty-six patients were enrolled in this Phase I trial. Thirty-five eligible patients were treated every 21 days in cohorts of at least three patients and were assessable for toxicity. One patient was ineligible due to hyperbilirubinemia. Stepwise dose escalations of edatrexate were administered until grade >3 nonhematological dose-limiting toxicities were reported. The initial dose level of edatrexate was 180 mg/m2; subsequent cohorts were treated with escalating doses of edatrexate (210, 240, 270, 300, 350, and 400 mg/m2). Edatrexate was administered by i.v. infusion over 1 h. Paclitaxel was administered 24 h later at a fixed dose of 175 mg/m2 as a 3-h infusion with standard dexamethasone, diphenhydramine, and cimetidine premedication. The MTD of edatrexate was reached at the 350 mg/m2 level in this study. Grade 3 diarrhea was seen in one patient at the 300 and 400 mg/m2 dose levels, requiring dose reductions. Two patients experienced grade 4 stomatitis at the 400 mg/m2 dose level and also required dose reduction, establishing the MTD as 350 mg/m2. Grade 3 nausea and vomiting were noted in two of three patients at the highest dose level. Of 35 patients, 4 patients reported grade 3 myalgias and 1 patient reported grade 3 neurosensory complaints, which were seen mostly at the 350 and 400 mg/m2 dose levels; however, 1 patient reported grade 3 myalgias at 180 mg/m2. No cumulative neurotoxicity was observed, and no patient experienced an allergic reaction to paclitaxel. In 23 patients with bidimensionally measurable disease, there were four complete (17%) and seven partial responses, with an overall response rate of 48% (95% confidence interval, 27-69%). All of the responses were seen in patients who had not received prior chemotherapy for stage IV disease. The median duration of response was not assessable because many responding patients went on to receive high-dose chemotherapy treatment with stem cell support. The combination of edatrexate and paclitaxel for treatment of metastatic breast cancer is a feasible and safe regimen. The MTD of edatrexate was 350 mg/m2 when combined with a 3-h infusion of paclitaxel (175 mg/m2) given 24 h later. Activity was noted even among patients who had relapsed shortly after receiving methotrexate- and/or doxorubicin-containing adjuvant regimens. Additional studies evaluating the sequences and dosing schema for this combination are warranted to improve the response proportion and define the duration of the response.