Castration-resistant prostate cancer: systemic therapy in 2012

Prostate cancer is the most common non-cutaneous neoplasm in the male population worldwide. It is typically diagnosed in its early stages, and the disease exhibits a relatively indolent course in most patients. Despite the curability of localized disease with prostatectomy and radiation therapy, some patients develop metastatic disease and die. Although androgen deprivation is present in the majority of patients with metastatic prostate cancer, a state of androgen resistance eventually develops. Castration-resistant prostate cancer, defined when there is progression of disease despite low levels of testosterone, requires specialized care, and improved communication between medical and urologic oncologists has been identified as a key component in delivering effective therapy. Despite being considered a chemoresistant tumor in the past, the use of a prostate-specific antigen has paved the way for a new generation of trials for castration-resistant prostate cancer. Docetaxel is a life-prolonging chemotherapy that has been established as the standard first-line agent in two phase III clinical trials. Cabazitaxel, a novel taxane with activity in cancer models resistant to paclitaxel and docetaxel, is the only agent that has been compared to a chemotherapy control in a phase III clinical trial as a second-line therapy; it was found to prolong the overall survival of patients with castration-resistant prostate cancer previously treated with docetaxel when compared to mitoxantrone. Other agents used in this setting include abiraterone and sipuleucel-T, and novel therapies are continually being investigated in an attempt to improve the outcome for patients with castration-resistant prostate cancer

The onco-psychiatry in breast cancer: considerations about the female matter

Os autores revisaram amplamente a literatura em relação aos fatores psiquiátricos envolvendo o câncer de mama. Dentro da linha de raciocínio mestra dos tratamentos cirúrgico e oncológico dessas pacientes, ressalta-se seu impacto sobre a saúde mental. Aspectos como possibilidades cirúrgicas, imagem corporal e impacto sobre auto-estima e sexualidade, tratamentos sistêmicos e conseqüências físicas, tais como fadiga, náuseas e vômitos, foram discutidos. As diferenças entre os grupos etários submetidos ao tratamento também foram relevadas, separando-se suas questões. Tópicos sobre a qualidade de vida sempre foram ressaltados. Questões sobre intervenções farmacológicas e psicoterapêuticas foram igualmente levantadas, incluindo medicina alternativa.The authors performed a broad literature review about psychiatric factors in breast cancer. Inside the master reasoning of the surgical and oncological treatments, an emphasis was made on heir impact over the mental health. Aspects like surgical possibilities and body image and its impact over the self-estime and sexuality and systemic treatments and their physical consequences, like fatigue, nausea and vomiting were discussed. The differences between the aged groups treated also were considered, separating their issues. Topics about Quality of Life was always considered. Questions about pharmacological and psychotherapeutical approach were considered too, including alternative medicine

Phase II trial of humanized anti-Lewis Y monoclonal antibody for advanced hormone receptor-positive breast cancer that progressed following endocrine therapy

OBJECTIVES: The Lewis-Y antigen is expressed in 44%-90% of breast cancers (BCs). The expression of the antigen in carcinoma tissue differs from that in normal tissues. This study aimed to evaluate the clinical benefit of the humanized anti-Lewis Y monoclonal antibody, hu3S193, in advanced hormone receptor-positive and Lewis Y-positive BC after administration of endocrine therapy (ET). METHODS: A single-arm phase II study was conducted in seven centers. Patients with advanced hormone receptor-positive BC who failed first-line ET were included. The inclusion criterion was the observation of tumoral expression of the Lewis Y antigen during immunohistochemistry. The treatment comprised hu3S193 antibody administration at weekly intravenous doses of 20 mg/m2 for 8-week cycles. The primary endpoint was the clinical benefit rate. ClinicalTrials.gov NCT01370239. RESULTS: The study stopped accrual following an unplanned interim analysis as the hu3S193 antibody lacked sufficient activity to justify continuation of the study. Twenty-two patients were enrolled, of whom 21 were included in the efficacy analysis. The clinical benefit rate was 19%, with four patients presenting with stable disease after 24 weeks. One patient with prolonged stable disease received medication for over 2 years. No partial or complete responses were observed. The median time to progression and overall survival was 5.4 and 37.5 months, respectively. CONCLUSIONS: The humanized anti-Lewis Y monoclonal antibody, hu3S193, exhibited insufficient activity in this cohort. However, the possibility of activity in a more strictly selected subgroup of patients with higher levels of Lewis Y tumoral expression cannot be overlooked

Current management and future directions in the treatment of advanced renal cell carcinoma-a latin american perspective: 10 years in review

ABSTRACT The worldwide incidence of kidney cancer is estimated at 337,860 new cases per year in the International Agency for Research on Cancer's GLOBOCAN 2012 update, with an estimated 143,369 deaths annually. Over the past 10 years, there have been significant advances in the treatment of advanced/metastatic renal cell carcinoma, including the development of targeted therapies. Currently recommended first-line treatments include sunitinib, temsirolimus, bevacizumab plus interferon, and pazopanib, or high-dose interleukin-2 or sorafenib for selected patients. Recommended second-line treatments include all of the above agents, as well as everolimus and axitinib. Unfortunately, combination therapies have generally resulted in increased toxicity and little improvement in efficacy. Recent studies focused on identification of predictive biomarkers for responses to specific targeted therapies and have not been successful to date. Despite recent advances in targeted treatment for metastatic renal cell carcinoma, important questions regarding biomarkers of efficacy, and optimal combination and sequencing of agents remain to be answered. This paper reviews literature concerned with first-and second-line treatment of metastatic renal cell carcinoma and will discuss key issues in Latin America

Paraneoplastic rheumatic syndromes

This article makes a review of the literature on paraneoplasticrheumatic syndromes. Rheumatic diseases may sometimeshave manifestations associated with the development of tumorprocesses, being considered paraneoplastic. Certain manifestationshave studies confi rming a strong association with malignancy;among these are hypertrophic osteoarthropathy, paraneoplasticpolyarthritis, dermatomyositis, and vasculitis. On the otherhand, chemotherapy and radiotherapy can induce rheumatologiccomplications in cancer patients

Impact of Pathology Review for Decision Therapy in Localized Prostate Cancer

Background: The Gleason score is an essential tool in the decision to treat localized prostate cancer. However, experienced pathologists can classify Gleason score differently than do low-volume pathologists, and this may affect the treatment decision. This study sought to assess the impact of pathology review of external biopsy specimens from 23 men with a recent diagnosis of localized prostate cancer. Methods: All external biopsy specimens were reviewed at our pathology department. Data were retrospectively collected from scanned charts. Results: The median patient age was 63 years (range: 46-74 years). All patients had a Karnofsky performance score of 90% to 100%. The median prostate-specific antigen level was 23.6 ng/dL (range: 1.04-13.6 ng/dL). Among the 23 reviews, the Gleason score changed for 8 (35%) patients: 7 upgraded and 1 downgraded. The new Gleason score affected the treatment decision in 5 of 8 cases (62.5%). Conclusions: This study demonstrates the need for pathology review in patients with localized prostate cancer before treatment because Gleason score can change in more than one-third of patients and can affect treatment decision in almost two-thirds of recategorized patients

Impact of Pathology Review for Decision Therapy in Localized Prostate Cancer

Background: The Gleason score is an essential tool in the decision to treat localized prostate cancer. However, experienced pathologists can classify Gleason score differently than do low-volume pathologists, and this may affect the treatment decision. This study sought to assess the impact of pathology review of external biopsy specimens from 23 men with a recent diagnosis of localized prostate cancer. Methods: All external biopsy specimens were reviewed at our pathology department. Data were retrospectively collected from scanned charts. Results: The median patient age was 63 years (range: 46-74 years). All patients had a Karnofsky performance score of 90% to 100%. The median prostate-specific antigen level was 23.6 ng/dL (range: 1.04-13.6 ng/dL). Among the 23 reviews, the Gleason score changed for 8 (35%) patients: 7 upgraded and 1 downgraded. The new Gleason score affected the treatment decision in 5 of 8 cases (62.5%). Conclusions: This study demonstrates the need for pathology review in patients with localized prostate cancer before treatment because Gleason score can change in more than one-third of patients and can affect treatment decision in almost two-thirds of recategorized patients

Gefitinib for patients with advanced non-small cell lung cancer treated on the expanded access program: a single institution experience

Objective: A retrospective analysis of patients with advanced nonsmallcell lung cancer treated with gefitinib on an expanded accessprogram. Methods: Patients with advanced non-small cell lung cancerand Karnofsky performance status ≥ 50% were allowed to enroll. Theyreceived gefitinib 250 mg orally once a day. No other systemic anticancertreatment was allowed during the trial. Results: From June 2002 toApril 2003, 31 patients were included. The age range was 38 to 84years, with 20 men and 11 women. The median Karnofsky performancestatus was 80% and 25 patients had a history of smoking. Thirty patientswere clinical stage IV and one patient was stage IIIB. The objectiveresponse rate was 14%. There was no complete response. An additional36% of patients (n=10) had stable disease for more than 6 months,giving a response plus disease stabilization rate of 50%. The medianprogression free survival was 3.6 months, and the median overallsurvival was 4 months. The one year survival rate was 19%. Toxicitieswere mild in this cohort, with grade 1 (42%) and 2 (11%) diarrhea andgrade 1 rash (16%) being the most commonly observed side effects.Conclusions: Despite the small sample, our data are similar to publishedtrials, confirming efficacy in a setting of pretreated patients and tolerableside effects. In this study patients had to meet only a few essentialeligibility criteria for enrollment, making our data reproducible andapplicable to patients seen in a community setting