Monoclonal antibody inhibitors of the epidermal growth factor receptor (EGFR) have been shown to improve outcomes for patients with metastatic colorectal cancer (mCRC) without RAS gene mutations. However, treatment with anti-EGFR agents can be associated with toxicities of the skin, nails, hair, and eyes. Because these dermatologic toxicities can result in treatment discontinuation and affect patient quality of life, their management is an important focus when administering anti-EGFR monoclonal antibodies. The present systematic review describes the current data reporting the nature and incidence of, and management and treatment options for, dermatologic toxicities occurring during anti-EGFR treatment of mCRC. A search of the National Library of Medicine PubMed database from January 1, 2009, to August 18, 2016, identified relevant reports discussing dermatologic toxicity management among patients with mCRC receiving anti-EGFR therapy. The studies were grouped by type and rated by level of evidence using the GRADE approach developed by the Agency for Healthcare Research and Quality. Overall, 269 reports were reviewed (nonrandomized trials, n = 120; randomized trials, n = 31; retrospective studies, n = 15; reviews, n = 39). Dermatologic toxicity of any grade occurs in most patients who receive anti-EGFR therapy; approximately 10% to 20% of patients experienced grade 3/4 toxicity. The most common dermatologic toxicities include papulopustular/acneiform rash, xerosis, and pruritus; however, nail changes, hair abnormalities, and ocular conditions also occur. Guidance for managing these toxicities includes the use of inexpensive emollient ointments and moisturizers, avoidance of sun exposure, avoidance of irritants, and the use of short showers. Several studies also found that preemptive treatment was more effective than reactive treatment at limiting the incidence and severity of skin toxicity. With appropriate treatment, the dermatologic toxicities associated with anti-EGFR monoclonal antibody therapy can be managed, minimizing patient discomfort and the need for therapy interruption and/or discontinuation. Additionally, preemptive treatment can reduce dermatologic toxicity severity, ultimately yielding better quality of life.
Purpose: LV305 is a modified, third-generation, nonreplicating, integration-deficient lentivirus-based vector designed to selectively transduce dendritic cells in vivo. LV305 induces expression of the New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) cancer testis antigen in dendritic cells, promoting immune responses against NY-ESO-1–expressing tumors. This phase I study evaluated the safety, immunogenicity, and preliminary efficacy of LV305 in patients with sarcoma or other solid tumors. Patients and Methods: Adults with previously treated, advanced, NY-ESO-1–positive solid tumors and limited tumor burden were eligible. LV305 was administered every 3 weeks by intradermal injection in four dose cohorts (Cohort 1: 108 vector genomes (vg) x 3 doses; Cohorts 1A, 2, and 3: 108 vg, 109 vg, 1010 vg x 4 doses). Results: Thirty-nine patients were enrolled: 3 patients each in Cohorts 1, 1A, and 2, and 30 patients in Cohort 3. No dose-limiting toxicities were observed. Tumor types included sarcoma (n = 24), ovarian (n = 8), melanoma (n = 6), and lung cancer (n = 1). All treatment-related adverse events were grade 1 or 2. Common treatment-related adverse events were fatigue (49%), injection site reactions (46%), and myalgia (21%). The disease control rate was 56.4% in all patients and 62.5% in sarcoma patients. One patient with synovial sarcoma achieved a partial response lasting >36 months. Anti–NY-ESO-1-specific CD4+ and/or CD8+ T cells were induced in 57% of evaluable sarcoma patients. Induction of an anti–NY-ESO-1 immune response was associated with improved 1-year survival in an exploratory analysis. Conclusions: This first-in-class, first-in-human study of LV305 demonstrated a favorable safety profile, induction of antigen-specific responses, and potential clinical activity in patients with advanced cancer.
PurposeIn 1997, Vogelzang et al. reported that 61 % of patients with cancer indicated fatigue impacted daily life more than pain, and only 37 % of oncologists shared this perception. We provide an update to this study, which can help prioritize symptom assessment and management in the clinic. Study aims were to determine and compare perceptions of patients with cancer and health care providers (HCPs) of the impact of fatigue and pain.MethodsA random sample of patients with cancer was recruited in the USA by Harris Poll Online and Schlesinger Associates. Oncology HCPs were recruited by Food and Drug Research, Inc. and Toluna, Inc.ResultsFrom June to November 2012, 550 of 1122 eligible patients (49 %), 400 of 533 eligible oncologists (75 %), and 400 of 617 eligible oncology nurses (65 %) completed a survey. Of patients, 58 % reported that fatigue affected their daily lives more than pain while undergoing treatment with chemotherapy versus 29 % of oncologists and 25 % of oncology nurses that had this perception. Ninety-eight percent of patients reported experiencing fatigue, whereas 72 % of oncologists and 84 % of oncology nurses thought this was the case. Eighty-six percent of patients reported pain while undergoing treatment with chemotherapy, whereas 36 % of oncologists and 51 % of oncology nurses believed this occurred. Nausea and vomiting felt by HCPs were the most concerning symptoms for patients (88 %).ConclusionsThis study shows the importance of assessing symptoms by direct patient report during chemotherapy treatment. HCPs continue to underestimate the prevalence and importance of fatigue and pain for patients with cancer, a finding that may alter the management of treatment-related symptoms and may influence the development of patient symptom management plans.Electronic supplementary materialThe online version of this article (doi:10.1007/s00520-016-3275-2) contains supplementary material, which is available to authorized users.
Synovial sarcoma (SS) is an aggressive malignancy which accounts for approximately 5–10% of all soft-tissue sarcomas. SS has pathologic and genomic characteristics that define it as a distinct subtype of soft tissue sarcoma (STS). STS subtypes continue to be recognized as distinct entities with specific characteristics, including differential chemo-sensitivity. The objective of this study was to conduct a descriptive review of current data on survival outcomes of systemic anti-cancer therapy specific to SS. A systematic literature review was conducted, using a custom search strategy to search EMBASE, Medline and CENTRAL for clinical trials and observational studies reporting overall survival (OS), progression-free survival (PFS) and/or response for cohorts of at least 50 SS patients. We identified 28 studies meeting these criteria, 25 of which were retrospective studies. Only three prospective studies were identified. Survival reports varied widely between studies based on the population, in particular on the disease stage, and reporting was heterogeneous in terms of the time points reported on. For patients with localized disease, reports of five-year PFS ranged from 26% to 80.7% and five-year OS from 40% to 90.7%, whereas five-year OS for patients with metastatic disease was very low at around 10%; and in one case, 0% was reported. Only four of the included publications reported outcomes by type of systemic anti-cancer therapy received. Our study draws attention to the fact that additional prospective studies to better define the most appropriate treatment for SS in all stages and lines of therapy are still needed.
These results provide insight into novel risk factors for chemotherapy dose modification that may inform clinicians on management strategies to optimize treatment outcomes.
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