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Advanced renal cell carcinoma (RCC) remains a challenging oncologic disease to treat despite advancements in therapeutics. Nonetheless, the development of tyrosine kinase inhibitors (TKIs) and immunotherapy has drastically altered the treatment landscape for advanced RCC over the past decade. The current standard-of-care treatment for advanced RCC involves combination TKI and immunotherapy regimens including cabozantinib and nivolumab as studied in the CheckMate 9ER trial. This review summarizes the preclinical and clinical evidence that led to the CheckMate 9ER study, as well as pertinent study aspects such as treatment efficacy, adverse events and patient-related outcomes.
Kidney cancer that has spread to organs and other parts of the body outside of the kidney remains a challenging disease to treat. The treatment of advanced kidney cancer has changed over the past decade with the approval of oral therapies called tyrosine kinase inhibitors and more recently immunotherapy, which utilizes the immune system to treat cancer. A new combination therapy employing cabozantinib and nivolumab has been shown to help patients with advanced kidney cancer live longer and have improvements in quality of life. This new combination therapy is now commonly used to treat advanced kidney cancer.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Nivolumabe/uso terapêutico , Neoplasias Renais/patologia , Anilidas/efeitos adversosRESUMO
Patients with coccidioidal meningitis require lifelong antifungal therapy. Cumulative toxicity and lack of antifungal efficacy require salvage therapy in the treatment of some patients. In a retrospective review of nine patients with coccidioidal meningitis treated with isavuconazole, successful therapy was seen in three patients and stable disease was confirmed in six patients. Isavuconazole may be a useful addition to the therapeutic choices currently available for coccidioidal meningitis.
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Antifúngicos/uso terapêutico , Coccidioidomicose/tratamento farmacológico , Meningite Fúngica/tratamento farmacológico , Nitrilas/uso terapêutico , Piridinas/uso terapêutico , Triazóis/uso terapêutico , Adulto , Antifúngicos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Piridinas/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Triazóis/efeitos adversosAssuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Humanos , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Estresse Financeiro , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/patologia , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMO
BACKGROUND: Pemetrexed is a commonly used treatment for platinum-resistant advanced urothelial carcinoma (UC) based on objective response rates of 8% and 28% in two small phase II studies. To address the discrepancy in reported response rates and to assess efficacy and toxicity outside of a clinical trial setting, we performed a large retrospective analysis of pemetrexed use at Memorial Sloan Kettering Cancer Center. We also investigated candidate prognostic factors for overall survival in this setting to explore whether the neutrophil-lymphocyte ratio (NLR) had independent prognostic significance. PATIENTS AND METHODS: Patients receiving pemetrexed for platinum-resistant advanced UC between 2008 and 2013 were identified. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) were used to determine response rate. Kaplan-Meier and Cox regression analyses were used to examine the association of various factors with efficacy and survival outcomes. Hematologic toxicity and laboratory abnormalities were recorded. RESULTS: One hundred and twenty-nine patients were treated with pemetrexed. The objective response rate was 5% (95% confidence interval: 1%-9%), and the median duration of response was 8 months. Median progression-free survival (PFS) was 2.4 months, and the 6-month PFS rate was 14%. There was no significant difference in response rate by age, Eastern Cooperative Oncology Group (ECOG) performance status, or number of prior therapies. On multivariable analysis, ECOG performance status (p < .01), liver metastases (p = .02), and NLR (p < .01) had independent prognostic significance for overall survival. CONCLUSION: This 129-patient series is the largest reported data set describing pemetrexed use in advanced UC. Activity was modest, although discovery of molecular biomarkers predictive of response would be valuable to identify the small subset of patients who do gain significant benefit. Overall, the data highlight the urgent need to develop novel therapies for these patients.
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Carcinoma de Células de Transição/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Pemetrexede/administração & dosagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/patologia , Ensaios Clínicos como Assunto , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Pemetrexede/efeitos adversos , Platina/administração & dosagem , Prognóstico , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologiaRESUMO
BACKGROUND: Due to encouraging pre-clinical data and supportive observational studies, there has been growing interest in applying cardiovascular drugs (including aspirin, angiotensin-converting enzyme [ACE] inhibitors, statins, and metformin) approved to treat diseases such as hypertension, hyperlipidemia, and diabetes mellitus to the field of oncology. Moreover, given growing costs with cancer care, these medications have offered a potentially more affordable avenue to treat or prevent recurrence of cancer. We sought to investigate the anti-cancer effects of drugs repurposed from cardiology or anti-inflammatories to treat cancer. We specifically evaluated the following drug classes: HMG-CoA reductase inhibitors (statins), cyclo-oxygenase inhibitors, aspirin, metformin, and both angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors. We also included non-steroidal anti-inflammatory drugs (NSAIDs) because they exert a similar mechanism to aspirin by blocking prostaglandins and reducing inflammation that is thought to promote the development of cancer. METHODS: We performed a systematic literature review using PubMed and Web of Science with search terms including "aspirin," "NSAID," "statin" (including specific statin drug names), "metformin," "ACE inhibitors," and "ARBs" (including specific anti-hypertensive drug names) in combination with "cancer." Searches were limited to human studies published between 2000 and 2023. MAIN OUTCOMES AND MEASURES: The number and percentage of studies reported positive results and pooled estimates of overall survival, progression-free survival, response, and disease-free survival. RESULTS: We reviewed 3094 titles and included 67 randomized clinical trials. The most common drugs that were tested were metformin (n = 21; 30.9%), celecoxib (n = 20; 29.4%), and simvastatin (n = 8; 11.8%). There was only one study that tested cardiac glycosides and none that studied ACE inhibitors. The most common tumor types were non-small-cell lung cancer (n = 19; 27.9%); breast (n = 8; 20.6%), colorectal (n = 7; 10.3%), and hepatocellular (n = 6; 8.8%). Most studies were conducted in a phase II trial (n = 38; 55.9%). Most studies were tested in metastatic cancers (n = 49; 72.1%) and in the first-line setting (n = 36; 521.9%). Four studies (5.9%) were stopped early because of difficulty with accrual. The majority of studies did not demonstrate an improvement in either progression-free survival (86.1% of studies testing progression-free survival) or in overall survival (94.3% of studies testing overall survival). Progression-free survival was improved in five studies (7.4%), and overall survival was improved in three studies (4.4%). Overall survival was significantly worse in two studies (3.8% of studies testing overall survival), and progression-free survival was worse in one study (2.8% of studies testing progression-free survival). CONCLUSIONS AND RELEVANCE: Despite promising pre-clinical and population-based data, cardiovascular drugs and anti-inflammatory medications have overall not demonstrated benefit in the treatment or preventing recurrence of cancer. These findings may help guide future potential clinical trials involving these medications when applied in oncology.
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Carcinoma Pulmonar de Células não Pequenas , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias Pulmonares , Metformina , Humanos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Inflamatórios , Aspirina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Metformina/uso terapêuticoRESUMO
Recent findings reported for the phase 3 EV-302 trial indicate a survival benefit from enfortumab vedotin plus pembrolizumab versus chemotherapy in metastatic urothelial carcinoma. We discuss several key points regarding post-protocol therapies, extending the duration of therapy, toxicity, and costs, all of which may have a bearing on how physicians and patients balance the benefit against the potential harms associated with this regimen.
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Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Padrão de Cuidado , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Metástase Neoplásica , Taxa de Sobrevida , Antineoplásicos Imunológicos/uso terapêuticoRESUMO
Over the past five years (2019-2023), several new targeted therapies and immunotherapy has been approved in treating relapsed cervical, ovarian, and endometrial cancers. Concurrently, there has been growing recognition of financial toxicity associated with cancer care during this time period. As such, we reviewed FDA approvals from 2019 to 2013 and identified the following approvals in gynecologic oncology: pembrolizumab plus lenvatinib, pembrolizumab for recurrent endometrial cancer that is MSI-H/dMMR, tisotumab vedotin, dostarlimab as single-agent therapy, and dostarlimab plus chemotherapy. We focused on approvals for endometrial cancer, and conducted a cost-effectiveness analysis for combination options approved in treating recurrent or advanced endometrial cancer (i.e. pembrolizumab plus lenvatinib versus placebo; dostarlimab plus chemotherapy versus placebo), and found neither regimen was cost-effective at a willingness-to-pay of $100,000 per Equal Value of Life Years Gained (evLYG). While these costs may not necessarily be translated to an individual patient, these costs are absorbed by healthcare systems and insurance providers on a larger scale with downstream effects on individuals contributing to healthcare costs a whole.
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IMPORTANCE: There is an increasing number of cancer 'survivors' and increasing research into supportive care. However, it is unknown how patterns of attention and citation differ between supportive and non-supportive cancer care research. We sought to estimate the engagement of high-impact studies of supportive compared to non-supportive cancer care papers. METHODS: In a cross-sectional review of top oncology journals (2016-2023), we reviewed studies examining supportive care strategies and a frequency-matched random sampling of studies on non-supportive interventions. We compared data on social engagement metrics, as represented by Altmetric scores and citations and funding status, by supportive care or non-supportive care articles. RESULTS: We found overall Altmetric scores were no different between articles that did not test supportive care and those that did, with a numerically higher score for supportive care articles (86.0 vs 102; p=0.416). Other bibliometric statistics (such as the number of blogs, number of X users, and the number of X posts) obtained from Altmetric did not differ significantly between the two groups. Non-supportive cancer care papers had a significantly higher number of citations than supportive cancer care papers (45.6 in supportive care vs 141 in non-supportive care papers; p<0.001). A greater proportion of non-supportive cancer care papers were also supported by pharmaceutical companies compared to supportive cancer care papers (54.2â¯% vs 15.3â¯%; p<0.001). CONCLUSION: Though social media engagement is similar between supportive and non-supportive cancer care papers in high-impact journals, there is a significant difference in support from pharmaceutical companies and the number of citations.
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There is a rising trend in the consumption of dietary supplements, especially among adults, with the purpose of improving health. While marketing campaigns tout the potential health benefits of using dietary supplements, it is critical to evaluate the potential harmful effects associated with these supplements as well. The majority of the scarce research on the potential harmful effects of vitamins focuses on the acute or chronic toxicities associated with the use of dietary supplements. Quality research is still required to further investigate the risks of long-term use of dietary supplements, especially the risk of developing cancers. The present review concentrates on studies that have investigated the association between the risk of developing cancers and associated mortality with the risk of dietary supplements. Such an association has been reported for several vitamins, minerals, and other dietary supplements. Even though several of these studies come with their own shortcomings and critics, they must draw attention to further investigate long-term adverse effects of dietary supplements and advise consumers and healthcare providers to ponder the extensive use of dietary supplements.
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Urachal cancer is a rare malignancy of the urachus that is treated with surgical resection if localized and systemic chemotherapy for metastatic disease. Circulating tumor DNA (ctDNA) is a single-stranded or double-stranded DNA released by tumor cells into the blood and harbored the mutations of the original tumor, shedding new light on molecular diagnosis and monitoring of cancer. We report a case of resected localized urachal cancer with clear surgical margins and negative lymph node dissection but elevated ctDNA that progressed to metastatic disease. We also highlight the possibility of using ctDNA levels to assist in adjuvant therapy.
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BACKGROUND: Spinal cord compression (SCC) in metastatic prostate cancer (MPC) is a critical complication and multiple factors influence the optimal therapeutic strategy. We investigated the differences in practice patterns between teaching hospitals (TH) and non-teaching hospitals (NTH) across the United States. METHOD: Using the National Inpatient Sample Database (NIS), we performed a retrospective study on hospitalizations with MPC and SCC between 2016 and 2020 in US. We compared demographic factors, comorbidities, treatment modalities, duration of hospitalization, financial expenditures, and mortality between TH and NTH. We also examined the patients' characteristics and outcomes in TH and NTH based on their chosen therapeutic strategy. RESULTS: We identified 11,380 admissions with metastatic prostate cancer and SCC; 9610 in TH and 1770 in NTH. The median cost of hospitalization was $21,922 in TH and $15,141 in NTH. Although the median age and Charlson comorbidity score did not differ between two groups, patients in TH were more likely to receive intervention (radiation or surgery) compared to NTH (Surgery: 28.2% in TH vs. 23.0% in NTH & Radiation: 12.1% in TH vs. 8.2% in NTH). Mortality was lower in TH than NTH (4.5% vs. 7.9%). In both TH and NTH, a higher proportion of patients with private insurance underwent surgery (TH: Surgery 25.1% vs. Radiation 18.8% & NTH: Surgery 27.0% vs. 6.9%). Black patients were more likely to receive radiation than surgery in TH (34.2% vs. 26.8%). CONCLUSION: This study showed a greater percentage of patients underwent surgical intervention at TH compared to NTH. Additionally, the type of insurance and racial background were associated with distinctive treatment approaches.
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Hospitais de Ensino , Neoplasias da Próstata , Compressão da Medula Espinal , Humanos , Masculino , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/terapia , Compressão da Medula Espinal/mortalidade , Estados Unidos/epidemiologia , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/mortalidade , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Hospitalização/estatística & dados numéricos , Hospitalização/economia , Idoso de 80 Anos ou maisRESUMO
Immune checkpoint inhibitors (ICIs) have transformed cancer care. Recently, atezolizumab gained its first global approval in a subcutaneous (SC) formulation by the UK medicines regulator, being notable as the first time an FDA- and/or European Medicines Agency (EMA)-approved ICI has been licensed via this administration route. Here, we discuss this approval, other SC ICIs in development, and the benefits and challenges of this administration route, including potential implications for patient care.
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Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , Injeções Subcutâneas , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Aprovação de DrogasRESUMO
BACKGROUND: Previous studies on Hispanic thyroid cancer cases show sex disparities and an increased prevalence of large tumor sizes and nodal involvement. Here, we characterized Hispanic thyroid cancer cases in California. METHODS: We identified thyroid cancer cases from 2010 to 2020 using the California Cancer Registry by sex, race/ethnicity, histology, TNM stage, tumor size, lymph node involvement, and Charlson comorbidity score. The age-adjusted incidence rate (AAIR) and age-adjusted mortality rate (AAMR) for all causes of death were calculated. A Cox proportional hazards regression analysis was performed to evaluate the mortality risk from all causes of death by race. RESULTS: Overall, 56,838 thyroid cancer cases were identified, including 29.75% in Hispanics. Hispanics had the highest female-to-male incidence rate ratio (IRR 3.54) and the highest prevalence of T3/T4 tumor size (28.71%), the highest N1 nodal status (32.69%), and the highest AAMR (0.79 per 100,000 people). After adjusting for demographic and tumor covariates, compared to non-Hispanic White people, Hispanic ethnicity, with an HR of 1.22 (95% CI 1.18-1.25, p < 0.0001), remained a significant independent contributor to mortality risk. CONCLUSIONS: Hispanics had the greatest female-to-male IRR ratio, a greater prevalence of advanced disease features at diagnosis, along with the highest AAMR and increased mortality risk despite adjustments for demographic and tumor covariates. Further investigation into other risk factors is needed.
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PURPOSE: We evaluated the retrieval rates and reproductive outcomes of percutaneous sperm retrieval according to the cause of obstructive azoospermia. MATERIALS AND METHODS: We retrospectively studied the records of 146 men with obstructive azoospermia who underwent sperm retrieval for intracytoplasmic sperm injection. Patients were grouped by the cause of obstruction, including 32 with congenital bilateral absence of the vas deferens, 59 with vasectomy and 55 with obstruction due to post-infection disease. Sperm were retrieved percutaneously from the epididymis or testis. We compared retrieval rates and intracytoplasmic sperm injection outcomes, including neonatal results, in the groups of men with obstructive azoospermia. RESULTS: The success of sperm retrieval was similar among the etiology groups, including 100% for congenital bilateral absence of the vas deferens, 96.6% for vasectomy and 96.3% for previous infection. Significantly fewer men in the congenital bilateral absence of the vas deferens group needed testicular aspiration compared to those in the post-infection and vasectomy groups (3.1% vs 23.6% and 30.5%, respectively, p <0.001). Sperm cryopreservation was possible in 26.7% of the cases and did not significantly differ among the groups. Live birth rates after sperm injection were similar in the congenital (34.4%), vasectomy (32.2%) and previous infection (36.4%) groups. Birth parameters, prematurity and low birth weight rates were comparable among the groups. CONCLUSIONS: Percutaneous sperm retrieval is an effective method to retrieve sperm in men with obstructive azoospermia irrespective of the cause of obstruction. The chance of achieving a live birth and the profile of neonates born after sperm injection do not seem to be related to the cause of obstruction.