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Background Cancer patients receive numerous medications, including antineoplastic agents, drugs for supportive care, and medications for comorbid illnesses. Therefore, they are at risk for drug interactions and duplicate prescribing. Methods A questionnaire eliciting information on demographics and medications taken in the previous 4 weeks was given to adult outpatients receiving systemic anticancer therapy for solid tumors. The Drug Interaction Facts software, version 4.0, was used to identify potential drug interactions and to classify them by level of severity (major, moderate, or minor) and the strength of scientific evidence for them (using categories [1-5] of decreasing certainty). Summary statistics and logistic regression were used to analyze the data. All statistical tests were two-sided. Results The survey was completed by 405 patients. We observed 276 potential drug interactions, and at least one potential interaction was identified in 109 patients (27%; 95% confidence interval [CI] = 23% to 31%). Of the potential interactions, 25 (9%) were classified as major and 211 (77%) as moderate. Nearly half (49%) of potential interactions were supported by level 1 or 2 scientific evidence. Most potential drug interactions (87%) involved non-anticancer agents such as warfarin, antihypertensive drugs, corticosteroids, and anti-convulsants, but some (n = 36, 13%) involved antineoplastic agents. In multivariable analysis, increased risk of receiving drug combinations in which there were potential drug interactions was associated with receipt of increasing numbers of drugs (odds ratio [OR] = 1.4 per additional drug, 95% CI = 1.26 to 1.58, P Conclusion Potential drug interactions were common among cancer patients and most often involved medications to treat comorbid conditions. Duplicate medications were infrequent.

In this Journal Club, Taboada and Riechelmann discuss the importance of a study outlining a novel neuroendocrine neoplasm classification system.

Pancreatic cancer has traditionally been associated with a dismal prognosis, even in early stages of the disease. In recent years, the introduction of newer generation chemotherapy regimens in the adjuvant setting has improved the survival of patients treated with upfront resection. However, there are multiple theoretical advantages to deliver early systemic therapy in patients with localized pancreatic cancer. So far, the evidence supports the use of neoadjuvant therapy for patients with borderline resectable pancreatic cancer. The benefit of this treatment sequence for patients with resectable disease remains elusive. In this review, we summarize the data on adjuvant therapy for pancreatic cancer and describe which evidence backs the use of neoadjuvant therapy. Additionally, we address important issues faced in clinical practice when treating patients with localized pancreatic cancer.

Introduction The role of primary prophylaxis (PP) with granulocyte colony-stimulating factor (G-CSF) for patients with metastatic pancreatic adenocarcinoma (MPA) treated with FOLFIRINOX is unknown. We aimed to compare the frequencies of grades 3 or 4 neutropenia (G3/4N) and febrile neutropenia (FN) and survival outcomes according to the use of PP.Methods This is a retrospective study. We included patients with pathologically confirmed MPA treated with FOLFIRINOX in first-line. Patients who received primary prophylaxis (PP group) were compared to patients who received secondary or no G-CSF (no-PP group). Overall survival (OS) and progression-free survival (PFS) were evaluated using the standard Cox proportional hazard model. To account for potential biases, we performed sensitivity analyses excluding patients who received secondary prophilaxis and treating G-CSF as a time-dependent covariate in extended Cox proportional hazard models.Results The study population consisted of 123 patients. PP was used by 75 patients (61.0%). G3/4 N occurred more frequently among patients without PP (10.7 vs 41.7%; P < .001). There was no difference in the frequency of FN between groups (5.3 vs 8.3%; P = .710). In multivariate analysis, PP was associated with a trend toward improved OS (HR = .66; 95% confidence interval [95% CI] .41 - 1.07; P = .094). In the multivariate model excluding patients with secondary prophylaxis (HR = .54; 95% CI 0.32 - .91; P = .022) and in the time-dependent model (HR = .47; 95% CI 0.28 - .80; P = .005), PP was associated with statistically superior OS.Conclusions Despite the reduction in the frequency of G3/4N, the risk of FN among patients treated with FOLFIRINOX without G-CSF is too low to justify its use in a routine basis. However, given the potential of G-CSF to improve survival in this setting, further studies are warranted to assess its role during treatment with FOLFIRINOX for patients with MPA.

Colorectal cancer is the third leading cause of cancer death in the United States. The American College of Gastroenterology recommends screening for first-degree relatives of patients diagnosed with colorectal cancer before the age of 50. A colonoscopy is one of the most commonly recommended exams due to its specificity and the possibility to resect pre-malignant lesions. Nevertheless, the rate of physician adherence to this recommendation is unknown.

ABSTRACTThe success of immunotherapies brings hope for the future of cancer treatment. Even so, we are faced with a new challenge, that of understanding which patients will respond initially and, possibly, develop resistance. The examination of the immune profile, especially approaches related to the immunoscore, may foretell which tumors will have a positive initial response. Ideally, the mutation load would also be analyzed, helping to reveal tumor associated antigens that are predictive of an effective cytolytic attack. However, the response may be hindered by changes induced in the tumor and its microenvironment during treatment, perhaps stemming from the therapy itself. To monitor such alterations, we suggest that minimally invasive approaches should be explored, such as the analysis of circulating tumor DNA. When testing new drugs, the data collected from each patient would initially represent an N of 1 clinical trial that could then be deposited in large databases and mined retrospectively for trends and correlations between genetic alterations and response to therapy. We expect that the investment in personalized approaches that couple molecular analysis during clinical trials will yield critical data that, in the future, may be used to predict the outcome of novel immunotherapies.

This study compared resource use and practice patterns in patients with advanced neuroendocrine tumors (NETs) on disease progression, across countries, and by tumor type.

Cancer-related fatigue is the most prevalent cancer symptom, reported in 50%–90% of patients and severely impacts quality of life and functional capacity. The condition remains underreported and often goes untreated. Guidelines suggest screening for fatigue at the initial visit, when the diagnosis of advanced disease is made, and at each chemotherapy session, as well as the identification of treatable contributing factors such as anemia, hypothyroidism, depression and sleep disorders. Brief assessment tools such as the Brief Fatigue Inventory or the Visual Analog Scale may be appropriate in the initial scoring of fatigue severity, but the initial approach to treatment usually requires a more comprehensive assessment, education, and the determination of an individualized treatment plan. Patients with moderate or severe fatigue may benefit from both pharmacological and non-pharmacological interventions, whereas mild fatigue that does not interfere with quality of life can be treated with non-pharmacological measures alone. Non-pharmacological measures that have shown to be promising include cognitive-behavioral interventions such as energy conservation and activity management (ECAM), exercise and perhaps sleep therapy. Many other modalities may be beneficial and can be used on an individual basis, but there is insufficient evidence to promote any single treatment. Pharmacological therapies that have shown to be promising include the psycho-stimulants methylphenidate and dexmethylphenidate, modafinil (in severely fatigued patients only), and erythropoietin-stimulating agents in patients with chemotherapy-associated anemia and hemoglobin levels < 10g/dL. Recently, our group reported impressive results with the use of the dry extract of Guarana (Paullinia cupana), with no significant side effects and at low cost, for the treatment of physical and mental cancer-related fatigue.

A fadiga relacionada ao câncer (FRC) é um dos sintomas mais prevalentes em pacientes com câncer, sendo reportada por 50% a 90% dos pacientes durante o curso da doença ou do seu tratamento, impactando na qualidade de vida de forma severa além de diminuir a capacidade funcional diária dos pacientes. Uma abordagem ampla deve ser realizada com orientações gerais sobre fadiga, além da determinação de um plano individualizado de abordagem terapêutica. Pacientes com fadiga moderada ou severa devem se beneficiar de ambas as medidas farmacológicas e não farmacológicas a serem adotadas, enquanto pacientes que apresentem fadiga leve que não interfira na qualidade de vida podem ser tratados com medidas não farmacológicas como única medida terapêutica. O tratamento não farmacológico se mostra promissor com o uso de terapias cognitivas-comportamentais (conservação de energia e organização de atividades diárias realizadas, ECAM), exercícios físicos e talvez terapias do sono. O tratamento farmacológico tem mostrado resultados promissores que incluem o uso de psicoestimulantes tais como metilfenidato e dexmetilfenidato, modanafil (em pacientes com fadiga severa) e agentes estimuladores de eritropoietina em pacientes com anemia associada à quimioterapia e hemoglobina menor que 10mg/dL. Além dessas drogas, o uso de Guaraná (Paullinia cupana) tem-se mostrado uma opção promissora, com efeitos benéficos no tratamento da fadiga física e mental relacionada ao câncer. Por ser uma opção sem efeitos colaterais significantes e uma planta nacional, torna-se atrativo considerando o fácil acesso a esta medicação por seu baixo custo e fácil adesão ao tratamento. O tratamento pode ser oferecido através de uma abordagem multimodal e multidisciplinar que individualize as opções terapêuticas dentro de um contexto que promova o diagnóstico acurado da FRC, além de um tratamento específico e adequado para cada paciente que apresente este sintoma tão importante e de grande impacto na qualidade de vida de pacientes com câncer.

With the growing number of new anticancer therapies, randomized phase II trials have been used more often in oncology. Although the primary objective of such trials is not to formally compare results between arms, this practice seems frequent. We sought to quantify the frequency of use of formal statistical testing or inference through the use of Pvalues and confidence intervals (CIs) in randomized phase II trials.

Gastric cancer (GC) is the fifth most common type of cancer worldwide with high incidences in Asia, Central, and South American countries. This patchy distribution means that GC studies are neglected by large research centers from developed countries. The need for further understanding of this complex disease, including the local importance of epidemiological factors and the rich ancestral admixture found in Brazil, stimulated the implementation of the GE4GAC project. GE4GAC aims to embrace epidemiological, clinical, molecular and microbiological data from Brazilian controls and patients with malignant and pre-malignant gastric disease. In this letter, we summarize the main goals of the project, including subject and sample accrual and current findings.

Patients with unresectable metastatic colorectal cancer live for a median of three years when treated with standard therapies. While the evidence guiding cancer-directed treatment of this disease comes from phase III trials that have mostly enrolled patients with good performance status, some patients present with poor clinical conditions. The best treatment for these patients remains to be determined. We performed a systematic review of the treatment outcomes of patients with metastatic colorectal cancer and poor performance status,defined as Eastern Cooperative Oncology Group performance status ≥2. Eligible articles were prospective or retrospective studies or case reports published in English, Portuguese or Spanish. We searched PubMed, EMBASE, LILACS and the Cochrane Library from onset until October 2017 using specific keywords for each search. We found a total of 18 publications, mostly case reports and retrospective studies (14 articles). One was an uncontrolled prospective trial, two were observational studies and one was an individual patient meta-analysis. Although some studies suggested benefits in terms of symptomatic response with standard chemotherapy, with good safety profiles when dose-reduced regimens were administered, a true survival gain could not be demonstrated. The scientific evidence for treating metastatic colorectal cancer patients with poor performance statusis scarce, and more studies evaluating treatment for this population are necessary since this condition is not uncommon in clinical practice, particularly in the public healthcare system and developing countries and among destitute populations.

Noncolorectal gastrointestinal (GI) malignancies are among the most frequently diagnosed cancers. Despite the undeniable progress in systemic treatments in recent decades, further improvements using cytotoxic chemotherapy seem unlikely. In this setting, recent discoveries regarding the mechanism underlying immune evasion have prompted the study of molecules capable of inducing strong antitumor responses. Thus, according to early data, immunotherapy is a very promising tool for the treatment of patients with GI malignancies. Noncolorectal GI cancers are a major public health problem worldwide. Traditional treatment options, such as chemotherapy, surgery, radiation therapy, monoclonal antibodies and antiangiogenic agents, have been the backbone of treatment for various stages of GI cancers, but overall mortality remains a major problem. Thus, there is a substantial unmet need for new drugs and therapies to further improve the outcomes of treatment for noncolorectal GI malignancies. “Next-generation” immunotherapy is emerging as an effective and promising treatment option in several types of cancers. Therefore, encouraged by this recent success, many clinical trials evaluating the efficacy of immune checkpoint inhibitors and other strategies in treating noncolorectal GI malignancies are ongoing. This review will summarize the current clinical progress of modern immunotherapy in the field of noncolorectal GI tumors.

Approximately 30-40% of patients with well-differentiated neuroendocrine tumors present with carcinoid syndrome, which is a paraneoplastic syndrome associated with the secretion of several humoral factors. Carcinoid syndrome significantly and negatively affects patients' quality of life; increases costs compared with the costs of nonfunctioning neuroendocrine tumors; and results in changes in patients' lifestyle, such as diet, work, physical activity and social life. For several decades, patients with neuroendocrine tumors and carcinoid syndrome have been treated with somatostatin analogues as the first-line treatment. While these agents provide significant relief from carcinoid syndrome symptoms, there is inevitable clinical progression, and new therapeutic interventions are needed. More than 40 substances have been identified as being potentially related to carcinoid syndrome; however, their individual contributions in triggering different carcinoid symptoms or complications, such as carcinoid heart disease, remain unclear. These substances include serotonin (5-HT), which appears to be the primary marker associated with the syndrome, as well as histamine, kallikrein, prostaglandins, and tachykinins.