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Actinic keratosis - review for clinical practice.
de Oliveira, ECV, da Motta, VRV, Pantoja, PC, Ilha, CSO, Magalhães, RF, Galadari, H, Leonardi, GR
International journal of dermatology. 2019;(4):400-407
Abstract
Actinic keratosis (AK) is a lesion that arises as a result of excessive exposure to solar radiation and appearing predominantly on Fitzpatrick phototype I and II skin. Given that some AKs evolve into squamous cell carcinoma, these lesions are considered premalignant in nature, occurring mostly in elderly men and immunosuppressed individuals chronically exposed to ultraviolet (UV) radiation. There are several mechanisms for the formation of AKs; among them are oxidative stress, immunosuppression, inflammation, altered proliferation and dysregulation of cell growth, impaired apoptosis, mutagenesis, and human papillomavirus (HPV). Through the understanding of these mechanisms, several treatments have emerged. Among the options for AK treatment, the most commonly used include 5-fluorouracil (5-FU), cryotherapy, diclofenac, photodynamic therapy (PDT), imiquimod (IQ), retinoids, and ingenol mebutate (IM). There have been recent advances in the treatment options that have seen the emergent use of newer agents such as resiquimod, betulinic acid, piroxicam, and dobesilate. The combination between therapies has presented relevant results with intention to reduce duration of therapy and side effects. All AK cases must be treated because of their propensity to transform into malignancy and further complicate treatment. In addition to medical or surgical care, education about sun exposure prevention remains the best and most cost-effective method for AK prevention. The objective of this article is to conduct a literature review of the clinical presentation of AK including advances in treatment options available.
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2.
Irinotecan- and 5-fluorouracil-induced intestinal mucositis: insights into pathogenesis and therapeutic perspectives.
Ribeiro, RA, Wanderley, CW, Wong, DV, Mota, JM, Leite, CA, Souza, MH, Cunha, FQ, Lima-Júnior, RC
Cancer chemotherapy and pharmacology. 2016;(5):881-893
Abstract
PURPOSE Intestinal mucositis and diarrhea are common manifestations of anticancer regimens that include irinotecan, 5-fluorouracil (5-FU), and other cytotoxic drugs. These side effects negatively impact therapeutic outcomes and delay subsequent cycles of chemotherapy, resulting in dose reductions and treatment discontinuation. Here, we aimed to review the experimental evidence regarding possible new targets for the management of irinotecan- and 5-FU-related intestinal mucositis. METHODS A literature search was performed using the PubMed and MEDLINE databases. No publication time limit was set for article inclusion. RESULTS Here, we found that clinical management of intestinal mucositis and diarrhea is somewhat ineffective at reducing symptoms, possibly due to a lack of specific targets for modulation. We observed that IL-1β contributes to the apoptosis of enterocytes in mucositis induced by 5-FU. However, 5-FU-related mucositis is far less thoroughly investigated with regard to specific molecular targets when compared to irinotecan-related disease. Several studies have proposed that a correlation exists between the intestinal microbiota, the enterohepatic recirculation of active metabolites of irinotecan, and the establishment of mucositis. However, as reviewed here, this association seems to be controversial. In addition, the pathogenesis of irinotecan-induced mucositis appears to be orchestrated by interleukin-1/Toll-like receptor family members, leading to epithelial cell apoptosis. CONCLUSIONS IL-1β, IL-18, and IL-33 and the receptors IL-1R, IL-18R, ST2, and TLR-2 are potential therapeutic targets that can be modulated to minimize anticancer agent-associated toxicity, optimize cancer treatment dosing, and improve clinical outcomes. In this context, the pathogenesis of mucositis caused by other anticancer agents should be further investigated.
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3.
Doublet chemotherapy vs. single-agent therapy with 5FU in elderly patients with metastatic colorectal cancer. a meta-analysis.
Landre, T, Uzzan, B, Nicolas, P, Aparicio, T, Zelek, L, Mary, F, Taleb, C, Des Guetz, G
International journal of colorectal disease. 2015;(10):1305-10
Abstract
BACKGROUND The clinical benefit of first-line doublet chemotherapy (including oxaliplatin or irinotecan) compared to single-drug therapy (5FU) in elderly patients (>70 or >75 years old) with metastatic colorectal cancer (MCRC) is controversial. Therefore, we undertook a meta-analysis of all published phase III studies. MATERIAL AND METHODS We performed a PubMed search using keywords metastatic colorectal cancer, phase III studies, oxaliplatin, irinotecan, survival. We also screened Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) proceedings. Few studies have been published corresponding to our inclusion criteria. The efficacy outcomes were overall survival (OS) and progression-free survival (PFS). Toxicity was also examined when available. Hazard ratios (HRs) with their 95 % confidence intervals (CI) were collected from the studies and pooled. By convention, HRs <1 corresponded to a better outcome for doublets. p values <0.05 were considered statistically significant. A fixed-effect model was used. We used Comprehensive Meta-Analysis Software (Biostat, Englewood, NJ, USA). RESULTS This meta-analysis (MA) included five original studies (Mitry and Venderbosch for CAIRO both assessing irinotecan, De Gramont and Seymour for FOCUS2 and Ducreux assessing oxaliplatin) and an already published MA (Folprecht) of four trials comparing FOLFIRI with 5FU (Saltz, Douillard, Köhne and Seymour). Our MA included 1225 patients (70 % men). For age, we chose a cut-off of 70 years for oxaliplatin and a cut-off of 75 years for irinotecan. The performance status (PS) score was 0-1 in about 90 % of patients except for the studies by Mitry and Seymour FOCUS2 which both included 30 % of PS2 patients. Overall, doublet chemotherapy, compared to 5FU alone, did not improve OS (HR = 1.00; CI: 0.89-1.13) but significantly improved PFS (HR = 0.82; CI: 0.72-0.93). When assessed separately, FOLFIRI and FOLFOX both significantly improved PFS (HR = 0.83; 0.68-1.00 and HR = 0.81; 0.68-0.97, respectively). The main grade 3-4 toxicities for FOLFIRI were diarrhoea, nausea, vomiting and neutropenia, which occurred significantly more often than with 5FU alone. CONCLUSION Addition of oxaliplatin or irinotecan to 5FU in metastatic CRC significantly improved PFS in elderly patients more than 70 years old but was associated with an increased risk of toxicity as shown for irinotecan.
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4.
Is levoleucovorin an alternative to racemic leucovorin? A literature review.
Kovoor, PA, Karim, SM, Marshall, JL
Clinical colorectal cancer. 2009;(4):200-6
Abstract
PURPOSE Our purpose is to perform a comprehensive literature review of the use of levoleucovorin in gastrointestinal malignancies and to assess whether levoleucovorin is a reasonable alternative to racemic leucovorin. DESIGN This is an extensive literature review of levoleucovorin use in patients with gastrointestinal tract malignancies. Our review revealed 125 citations with abstracts in the English language, including 16 randomized, controlled trials; 40 case studies; and 69 nonrandomized, controlled trials that included 6 pharmacokinetic (PK)/pharmacodynamic studies with 1 population PK study. RESULTS Upon our review, there were 2 randomized controlled trials that directly compared racemic leucovorin with levoleucovorin. Goldberg et al noted that there was no statistically significant difference between time to progression (P = .78) and time to death (P = .57). Furthermore, Scheithauer et al again noted no significant difference in terms of response rates (25% vs. 32%; P = .25), median survival time (15 months vs. 14.5 months; P = .28), overall survival at 1 year (58.3% vs. 60.6%; P = .72), and probability of survival at 2 years (15.3% vs. 23%; P = .16). In addition, multiple other studies, including randomized, controlled; nonrandomized, controlled; and case studies, demonstrate similar efficacy and tolerability between the use of racemic leucovorin or levoleucovorin as a modulator of 5-FU. CONCLUSION In many studies of patients with gastrointestinal malignancies, levoleucovorin has been used interchangeably and solely for racemic leucovorin for 5-FU modulation. Our literature review demonstrates that levoleucovorin has similar efficacy and tolerability when compared with racemic leucovorin, whether used in combination with other chemotherapeutic agents or alone.
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5.
What's new in ... colorectal cancer. Meaningful progress in therapy options.
Polansky, M, Ross, AC
JAAPA : official journal of the American Academy of Physician Assistants. 2009;(4):51-2
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6.
The spectrum of 5-fluorouracil cardiotoxicity.
Dalzell, JR, Samuel, LM
Anti-cancer drugs. 2009;(1):79-80
Abstract
Cardiotoxicity is a rare but serious complication of 5-fluorouracil therapy. Coronary vasospasm and, less frequently, acute myocarditis have been identified as underlying mechanisms. We report a case of severe toxicity in a relatively young and fit male patient being treated for metastatic colonic adenocarcinoma displaying characteristics that cannot be explained by either mechanism alone.