Targeted Oncology 

About: Targeted Oncology is an academic journal published by Springer Science+Business Media. The journal publishes majorly in the area(s): Cancer & Medicine. It has an ISSN identifier of 1776-2596. Over the lifetime, 912 publications have been published receiving 17825 citations.

Skin toxicities associated with epidermal growth factor receptor inhibitors

Abstract: The use of epidermal growth factor receptor (EGFR) inhibitors in several epithelial tumors has increased considerably in recent years. Currently, they are approved in non-small cell lung cancer (NSCLC), pancreatic cancer, colorectal cancer and head and neck cancer. Skin toxicity is a class-specific side effect that is typically manifested as a papulopustular rash in the majority (45-100%) of patients receiving EGFR inhibitors. The skin toxicity is related to the inhibition of EGFR in the skin, which is crucial for the normal development and physiology of the epidermis. Although rarely life-threatening, skin toxicity may cause significant physical and psycho-social discomfort. Nevertheless, the presence and severity of skin rash is associated with improved clinical efficacy in patients receiving EGFR inhibitors. The goal of managing EGFR inhibitor-associated skin toxicity is to minimize the detrimental effects of the rash on patients' quality of life and treatment course without antagonizing the clinical efficacy of EGFR inhibitors. There is currently no evidence-based treatment guideline to prevent or treat the EGFR inhibitor-associated skin toxicities. Expert panels recommend a proactive, multidisciplinary approach that includes patient education and the use of a grade-based treatment algorithm. Elucidation of the mechanisms of EGFR inhibitor-associated skin toxicity and development of mechanism-based novel therapies are urgently needed. Preclinical data suggest topical application of a potent phosphatase inhibitor menadione (Vitamin K3) can rescue the inhibition of EGFR and downstream signaling molecules in the skin of mice receiving systemic EGFR inhibitor erlotinib or cetuximab. A randomized, double-blinded, placebo-controlled study has been initiated to evaluate the clinical efficacy of menadione topical cream, in the treatment or prevention of EGFR inhibitor-induced skin toxicity.

Hyperbaric oxygen therapy and cancer—a review

Abstract: Hypoxia is a critical hallmark of solid tumors and involves enhanced cell survival, angiogenesis, glycolytic metabolism, and metastasis. Hyperbaric oxygen (HBO) treatment has for centuries been used to improve or cure disorders involving hypoxia and ischemia, by enhancing the amount of dissolved oxygen in the plasma and thereby increasing O2 delivery to the tissue. Studies on HBO and cancer have up to recently focused on whether enhanced oxygen acts as a cancer promoter or not. As oxygen is believed to be required for all the major processes of wound healing, one feared that the effects of HBO would be applicable to cancer tissue as well and promote cancer growth. Furthermore, one also feared that exposing patients who had been treated for cancer, to HBO, would lead to recurrence. Nevertheless, two systematic reviews on HBO and cancer have concluded that the use of HBO in patients with malignancies is considered safe. To supplement the previous reviews, we have summarized the work performed on HBO and cancer in the period 2004–2012. Based on the present as well as previous reviews, there is no evidence indicating that HBO neither acts as a stimulator of tumor growth nor as an enhancer of recurrence. On the other hand, there is evidence that implies that HBO might have tumor-inhibitory effects in certain cancer subtypes, and we thus strongly believe that we need to expand our knowledge on the effect and the mechanisms behind tumor oxygenation.

Sorafenib: A Review in Hepatocellular Carcinoma.

Abstract: Sorafenib (Nexavar®) is currently the only systemic agent approved for use in hepatocellular carcinoma (HCC). Its approval was based on the results of the pivotal SHARP and Sorafenib Asia-Pacific (AP) trials in Child-Pugh (CP) class A patients with advanced HCC, which showed significantly longer median overall survival (OS) and time to radiological progression (TTP) with sorafenib 400 mg twice daily than with placebo, with no significant between-group difference in the median time to symptomatic progression (TTSP). Subsequent results from real-world studies such as GIDEON also support the use of sorafenib in HCC, including in carefully selected CP class B patients, although the median OS achieved in these patients appears relatively short. Sorafenib has a well characterized tolerability and safety profile, with strategies available to prevent and manage adverse effects such as hand-foot skin reactions. In conclusion, sorafenib remains an important option for the treatment of HCC.

Prognostic Role of PD-L1 Expression in Renal Cell Carcinoma. A Systematic Review and Meta-Analysis

Abstract: Background Several clinical trials have reported that therapies targeting programmed death-1 (PD1) and its ligand (PD-L1) improve patient outcomes, while tumor response has been related to PD-L1 expression.

Carlumab, an anti-C-C chemokine ligand 2 monoclonal antibody, in combination with four chemotherapy regimens for the treatment of patients with solid tumors: an open-label, multicenter phase 1b study

Abstract: C-C chemokine ligand 2 (CCL2) stimulates tumor growth, metastasis, and angiogenesis. Carlumab, a human IgG1κ anti-CCL2 mAb, has shown antitumor activity in preclinical and clinical trials. We conducted a first-in-human phase 1b study of carlumab with one of four chemotherapy regimens (docetaxel, gemcitabine, paclitaxel + carboplatin, and pegylated liposomal doxorubicin HCl [PLD]). Patients had advanced solid tumors for which ≥1 of these regimens was considered standard of care or for whom no other treatment options existed. Dose-limiting toxicities included one grade 4 febrile neutropenia (docetaxel arm) and one grade 3 neutropenia (gemcitabine arm). Combination treatment with carlumab had no clinically relevant pharmacokinetic effect on docetaxel (n = 15), gemcitabine (n = 12), paclitaxel or carboplatin (n = 12), or PLD (n = 14). Total serum CCL2 concentrations increased post-treatment with carlumab alone, consistent with carlumab-CCL2 binding, and continued increase in the presence of all chemotherapy regimens. Free CCL2 declined immediately post-treatment with carlumab but increased with further chemotherapy administrations in all arms, suggesting that carlumab could sequester CCL2 for only a short time. Neither antibodies against carlumab nor consistent changes in circulating tumor cells (CTCs) or circulating endothelial cells (CECs) enumeration were observed. Three of 19 evaluable patients showed a 30 % decrease from baseline urinary cross-linked N-telopeptide of type I collagen (uNTx). One partial response and 18 (38 %) stable disease responses were observed. The most common drug-related grade ≥3 adverse events were docetaxel arm—neutropenia (6/15) and febrile neutropenia (4/15); gemcitabine arm—neutropenia (2/12); paclitaxel + carboplatin arm—neutropenia, thrombocytopenia (4/12 each), and anemia (2/12); and PLD arm—anemia (3/14) and stomatitis (2/14). Carlumab could be safely administered at 10 or 15 mg/kg in combination with standard-of-care chemotherapy and was well-tolerated, although no long-term suppression of serum CCL2 or significant tumor responses were observed.