Vitamin D and colorectal cancer - A practical review of the literature.

Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in the United States and the second cause worldwide. Its incidence rates have been decreasing in the overall population in the US in the past few decades, but with increasing rates in the population younger than 50 years old. Environmental factors are supposed to be involved in the development of the disease, with strong evidence favoring an influence of the diet and lifestyle. A diet high in red meat and calories, and low in fiber, fruits and vegetables increases the risk of CRC, as well as physical inactivity. The influence of low calcium intake and low levels of vitamin D on the risk of the disease and on the clinical outcomes of CRC patients has also been investigated. Hypovitaminosis D has been highly prevalent worldwide and associated with several chronic diseases, including malignancies. Vitamin D is a steroid hormone with the main function of regulating bone metabolism, but with many other physiological functions, such as anti-inflammatory, immunomodulatory, and antiangiogenic effects, potentially acting as a carcinogenesis inhibitor. In this review, we aim to describe the relation of vitamin D with malignant diseases, mainly CRC, as well as to highlight the results of the studies which addressed the potential role of vitamin D in the development and progression of the disease. In addition, we will present the results of the pivotal randomized clinical trials that evaluated the impact of vitamin D supplementation on the clinical outcomes of patients with CRC.

Efficacy and Safety Associated With Immune Checkpoint Inhibitors in Unresectable Hepatocellular Carcinoma: A Meta-analysis.

Importance: Immune checkpoint inhibitors (ICIs) have yielded conflicting results in hepatocellular carcinoma (HCC). The overall effect of ICIs compared with standard therapies in unresectable HCC requires more research. Objective: To estimate the efficacy and safety associated with ICIs compared with standard therapies in patients with unresectable HCC. Data Sources: PubMed, Cochrane Library, Web of Science, Latin American and Caribbean Health Sciences Literature, and American Society of Clinical Oncology and European Society of Medical Oncology meeting proceedings were systematically searched. Reference lists from studies selected by electronic searching were manually searched to identify additional relevant studies. The search included literature published or presented from February 2010 to February 2020. Study Selection: From December 2019 to February 2020, independent reviewers evaluated each database, scanning the title, abstract, and keywords of every record retrieved. Full articles were further assessed if the information given suggested that the study was a randomized clinical trial (RCT) comparing ICIs vs standard therapies in the treatment of unresectable HCC. Data Extraction and Synthesis: The full text of the resulting studies and extracted data were reviewed independently according to PRISMA guidelines. Summary hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS) were calculated by a random-effects model. The likelihood of ICIs being associated with overall response rate (ORR) and treatment-related adverse events (TRAEs) was expressed by odds ratios (ORs) using a random-effects model. Main Outcomes and Measures: The main outcomes were OS, PFS, ORR, and TRAEs. Results: Of 1836 studies yielded by the search, 3 were retained, totaling 1657 patients (985 treated with ICIs vs 672 receiving standard treatment). Two studies evaluated ICIs as monotherapy, and 1 study investigated the combination of ICIs with bevacizumab. Compared with standard therapies (sorafenib in first-line therapy or placebo in second-line therapy), ICIs were associated with significantly improved OS (HR, 0.75; 95% CI, 0.62-0.92; P = .006), PFS (HR, 0.74; 95% CI, 0.56-0.97; P = .03), and ORR (OR, 2.82; 95% CI 2.02-3.93; P < .001). The probability of grade 3 or 4 TRAEs was lower with ICIs than with sorafenib (OR, 0.44; 95% CI, 0.20-0.96; P = .04). Conclusions and Relevance: This meta-analysis found superior efficacy and safety associated with ICIs compared with standard therapies and highlights the survival benefit associated with the combination of antiangiogenic therapy with ICIs in first-line systemic therapy of unresectable HCC.

Fluorouracil Bolus Use in Infusional Regimens Among Oncologists-A Survey by Brazilian Group of Gastrointestinal Tumors.

PURPOSE: The utility of administering fluorouracil (5-FU) in bolus in regimens of infusional 5-FU has been questioned. We aimed to quantify the use of 5-FU bolus in infusional regimens for gastrointestinal malignancies among Brazilian oncologists. METHODS: This was a cross-sectional electronic survey composed of eight multiple-choice questions sent to Brazilian oncologists during 14 days in February 2021. The survey instrument collected demographic data of participants and assessed practices in terms of 5-FU bolus use. We evaluated the association of demographic variables and 5-FU prescribing patterns with Fisher's exact test (odds ratio [OR]). RESULTS: The survey was completed by 332 medical oncologists. Overall, 37% were experienced oncologists and 32% were gastrointestinal specialists. In the first-line metastatic and in the adjuvant settings, 40% and 67% of oncologists always prescribe 5-FU bolus in infusional regimens, respectively. Experienced oncologists more frequently omit 5-FU bolus when compared with early-career oncologists, both in the metastatic (41% v 26%; OR, 1.98; P = .005) and adjuvant settings (28% v 14%; OR, 2.32; P = .003). In addition, more GI specialists remove 5-FU bolus when compared with generalists, but only in the metastatic setting (44% v 25%; OR, 2.33; P = .001). GI specialists are more likely to consider that treatment efficacy is not affected by 5-FU bolus withdrawal than are generalists (89% v 75%; OR, 2.65; P = .003). Most respondents (67%) keep leucovorin at the same doses when omitting 5-FU bolus, and only 16% always recommend dihydropyrimidine dehydrogenase testing. CONCLUSION: Our survey indicates that experience in oncology practice and percentage of time dedicated to treat GI cancers influence the prescription of 5-FU bolus in Brazil, with more frequent omission of it among experienced gastrointestinal specialists, particularly in the metastatic setting.

Literature review and practical aspects on the management of oxaliplatin-associated toxicity.

Colorectal cancer is currently a public health priority because it is the second leading cause of cancer deaths in Western countries. Combination regimes of oxaliplatin and infusional fluorouracil/leucovorin or capecitabine have emerged as important options in the palliative and adjuvant treatment of colorectal cancer. Although better tolerated than cisplatin, oxaliplatin displays a characteristic profile of adverse events whose recognition and management are essential for physicians who treat patients with colorectal cancer and other malignancies that benefit from the use of oxaliplatin. Peripheral neuropathy is probably the most frequent and clinically relevant adverse event associated with the use of oxaliplatin, and several measures have been proposed to mitigate this toxicity. Temporary interruption of oxaliplatin before limiting neurotoxicity develops during therapy is a potential approach to avoid the problem of oxaliplatin-associated neuropathy in patients with metastatic colorectal cancer. Calcium and magnesium infusions have no effect on chemotherapy efficacy and also constitute a useful approach in clinical practice. Finally, the incidence and severity of chronic peripheral neuropathy in patients treated with oxaliplatin may be reduced by the use of neuroprotective agents, for example, venlafaxine. Other adverse events, such as gastrointestinal and liver toxicity, thrombocytopenia, and hypersensitivity reactions, are also reviewed in this article, and suggestions are made for their management.