Chemotherapy induced extravasation: Incidence and possible predictors

Abstract

Background: Epidermal growth factor receptor (EGFR) inhibitors are a standard treatment for various malignant tumors, especially in colon cancer and lung cancer. The most common adverse reaction of EGFR inhibitors is skin toxicity, including acneiform rash, xerosis, paronychial inflammation, pruritus, photosensitivity, and hair/eyelash alterations. Even though EGFR inhibitor-related skin adverse events (ERSEs) are pre-dictive marker of EGFR inhibitors treatment survivals, those are frequently also the reason for premature termination of anti-EGFR therapy. It is therefore important to understand the mechanisms underlying the skin toxicities caused by EGFR inhibition to improve anti-EGFR-based cancer therapies and minimize debilitating side effects for patients. Methods: Twelve patients' ERSEs skin biopsies which were treated with EGFR inhibi-tors were compared to same numbers of controlled skin biopsies those who did not use EGFR inhibitors. We evaluated Ki-67, EGFR, Melan-A, interleukin-17 (IL-17), and tumor necrosis factor-a (TNF-a) expression based on immunohistochemical (IHC) stains between 2 groups. Among them, five patients were treated with EGF ointment for ERSE. We also observed skin changes before and after EGF ointment. Results: Control and ERSE group's Ki-67 expression of epidermis were 40.8% vs 21.2% (P ¼ 0.015). EGFR presentation range of epidermis was 98.3% vs 84.6% in control and ERSEs group, respectively (P ¼ 0.001). We could observe 14.2% vs 8.1% (P ¼ 0.069) of Melan-A IHC stain. In the IL-17, ERSE group's IL-17 expression intensity (16.1) was higher than control group (9.8) (P ¼ 0.038). Much higher TNF-a expression intensity (13.3) was also observed in ERSE group compared control group (7.9) (P ¼ 0.037). After treatment with EGF ointment of 5 patients, values of Ki-67, EGFR, Melan-A, IL-17, and TNF-a were changed to 28%, 94%, 8.2%, 12.5 and 10, respectively. Conclusions: Treatment with EGFR inhibitors decreased expression of Ki-67 and EGFR in the patients' dermis. This seems to lead to secondary inflammation of the skin. The treatment of EGF ointment for ERSEs is thought to normalize EGFR level and the inflammatory response to some extent. Background: The emetogenic classification of antineoplastic agents has provided a framework for defining antiemetic treatment recommendations in international guidelines. The most widely used classification schema identified four emetic risk levels. However, information on the emetogenicity of each chemotherapeutic regimen is insufficient. We previously reported that the emetic risk of pemetrexed was higher than that of taxans. Risk factors for chemotherapy-induced nausea and vomiting (CINV) were also assessed in patients with lung cancer receiving carboplatin plus pemetrexed (CBDCAþPTX) or carboplatin plus paclitaxel (CBDCAþPEM), and the CINV incidence was compared between these two regimens. Methods: Data were pooled from two prospective studies, and propensity score matching was used to compare the CINV incidence between CBDCAþPTX and CBDCAþPEM groups. Risk factors for CINV were identified using logistic regression models. The pattern of CINV occurrence was evaluated by 7-day patient diary for recording CINV after the commencement of chemotherapy. Results: Among 240 evaluable patients, the CINV incidence was higher in the CBDCAþPEM group than in the CBDCAþPTX group at the delayed phase (nausea: 51.1% vs. 36.2%, P ¼ 0.040; vomiting: 23.4% vs. 14.9%, P ¼ 0.138). The pattern of delayed CINV occurrence peaked on days 5 and 4 for CBDCAþPEM and CBDCAþPTX regimens, respectively. Logistic regression analysis identified younger age, female sex, no alcohol consumption, two antiemetics, and CBDCAþPEM regimen as independent risk factors associated with delayed nausea, and female sex and two antiemetics for delayed vomiting. Conclusions: The emetic risk of CDBCAþPEM regimen was higher than that of CBDCAþPTX regimen. More aggressive antiemetic prophylaxis such as quadruple therapy, including olanzapine, may be considered in patients receiving CDBCAþPEM regimen. Background: Breast cancer survivors (BCS) often experience cancer-related fatigue (CRF), a distressing condition which does not have an effective standardised pharmacological intervention. Xiang Bei Yangrong Tang (XBYRT), a modified herbal traditional Chinese medicine (TCM) decoction, is formulated for the management of CRF in BCS. In this in vitro study, we evaluated the herb-enzyme inhibition for 9 of the herbal TCMs from the XBYRT formulation, on CYP2D6 activity. Methods: The XBYRT herbal components evaluated were Radix Astragaliseu Hedysari, Radix Codonopsis Pilosulae, Rhizoma Atractylodis Macrocephalae, Poria cocos, Radix Paeoniae Alba, Fructus Ligustri Lucidi, Rhizoma Cyperi, Radix Polygalae and Bulbus Fritillariae Thunbergii. Varying concentrations of the herbal TCMs were assayed for herb-enzyme inhibition using the Vivid P450 CYP2D6 assay kit. The percentage inhibition for the maximum XBYRT concentration and the half maximal inhibitory concentrations (IC 50) were determined. The maximum XBYRT concentration was calculated based on the total dosage of herbal components consumed, without accounting for first pass metabolism. The IC 50 was calculated using the non-linear regression from GraphPad Prism 5. Results: Assayed at the maximum XBYRT concentration, herbal components exhibiting the highest inhibition levels were Radix Codonopsis Pilosulae (56.8%), Poris cocos (45.0%), Fructus Ligustri Lucidi (42.9%) and Radix Paeoniae Alba (35.5%). The IC 50 values of these four herbal components were 481mg/ml, 572 mg/ml, 447 mg/ml and 475 mg/ml respectively. The other 5 herbal components exhibited <30% inhibition at the maximum XBYRT concentrations. Conclusions: Components of XBYRT display potential CYP2D6 enzymatic inhibition activities. Hence, caution should be taken with the concomitant usage of XBYRT with drugs that are CYP2D6 substrates such as tamoxifen. In vivo and clinical studies are required to ascertain the actual effects of these herbal components on drug metabolism. Background: Although extravasation (EV) is an established complication of parenteral chemotherapy, it often goes under-documented and underestimated. The incidence and severity of extravasation can be influenced by patient, drug or procedure related factors. An understanding of the risk factors and predictors promotes precaution during chemotherapy. Methods: A prospective study was conducted for one year in patients satisfying study criteria. Patient information such as demographics, history, disease, treatment regimen and EV related information was documented. Severity of EV was established using CTCAE 4.3. The captured data was subjected to appropriate statistical analysis using SPSS ver. 20. Results: Amongst the 217 patients reviewed 46(21.20%) experienced EV [Grade 2(67.39%) and Grade 3(32.61%)]. Cluster statistics revealed age, gender and ambula-tion to be the most important predictors.