Search

Background Delayed chemotherapy-induced nausea and vomiting (CINV) is not well controlled in patients with colorectal cancer (CRC) treated with oxaliplatin (L-OHP)-based chemotherapy. Whether adding a neurokinin-1 receptor antagonist to a first-generation 5HT3 antagonist (1st-5HT3RA) and dexamethasone (DEX) is beneficial in patients on L-OHP-based chemotherapy is controversial. It is unclear whether palonosetron (PALO) or aprepitant (APR) is more effective in controlling delayed CINV. We, therefore, investigated whether PALO+DEX (PALO group) or 1st-5HT3RA+DEX+APR (APR group) was more effective in controlling delayed CINV, as well as risk factors for delayed CINV, in patients with CRC treated with L-OHP-based chemotherapy. Methods We pooled data from two prospective observational studies in Japan and one phase III clinical trial and compared the incidence of CINV between the PALO and APR groups using propensity score-matched analysis. Risk factors for CINV were identified using logistic regression models. Results Among the 404 eligible patients, those in the PALO group showed a higher incidence of delayed CINV than those in the APR group (nausea: 43.4% vs. 32.4%, P = 0.061; vomiting: 12.5% vs. 4.4%, P = 0.017). The logistic regression analysis identified alcohol consumption, motion sickness, and PALO+DEX regimen as independent risk factors for delayed nausea, and female sex and PALO+DEX regimen as those for delayed vomiting. Conclusions Treatment with the three antiemetics, including APR, was more effective in controlling delayed CINV than prophylactic treatment with the two antiemetics, including PALO. Thus, patients with CRC receiving L-OHP-based chemotherapy should be treated with three antiemetics, including APR. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Nrf2 is a transcription factor associated with cancer growth and chemotherapy resistance. Nrf2 expression levels may be associated with prognosis of lung cancer, but previous results have been inconsistent. Methods The expression of Nrf2 in 1037 surgically resected lung adenocarcinoma (LAD) specimens was evaluated by immunohistochemistry. Nrf2 positivity was defined based on the intensity of stained nucleus of tumor cells on the tissue microarray: negative, weakly positive and strongly positive. The correlations between the Nrf2 expression and the prognosis, clinicopathological features and driver oncogene alterations were analyzed. Results The Nrf2 expression was negative in 236 (23%) of 1037 tumors, weakly positive in 444 (43%) and strongly positive in 357 (34%). The proportion of Nrf2-positive tumors was significantly higher in patients with pathological stage I (81%), tumors with EGFR mutations (87%) or KRAS mutations (87%), tumors without ALK fusions (78%) or ROS1 fusions (78%). The Nrf2 expression was not associated with the age, gender and smoking status. In multivariate analysis (Logistic regression model), pathological stage I, positive EGFR or KRAS mutation status were significant predictors of Nrf2 positivity. The increased expression of Nrf2 was associated with longer overall survival regardless of driver oncogene status. In multivariate analysis (Cox proportional hazards model), advanced age, male gender, advanced pathological stage and negative EGFR mutation status were significant unfavorable prognostic factors. Conclusions LADs that positively express Nrf2 have unique clinicopathological features. The increased expression of Nrf2 is a favorable prognostic marker in surgically resected LAD. Legal entity responsible for the study The authors. Funding AMED. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

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 (CBDCA+PTX) or carboplatin plus paclitaxel (CBDCA+PEM), 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 CBDCA+PTX and CBDCA+PEM 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 CBDCA+PEM group than in the CBDCA+PTX group at the delayed phase (nausea: 51.1% vs. 36.2%, P = 0.040; vomiting: 23.4% vs. 14.9%, P = 0.138). The pattern of delayed CINV occurrence peaked on days 5 and 4 for CBDCA+PEM and CBDCA+PTX regimens, respectively. Logistic regression analysis identified younger age, female sex, no alcohol consumption, two antiemetics, and CBDCA+PEM regimen as independent risk factors associated with delayed nausea, and female sex and two antiemetics for delayed vomiting. Conclusions The emetic risk of CDBCA+PEM regimen was higher than that of CBDCA+PTX regimen. More aggressive antiemetic prophylaxis such as quadruple therapy, including olanzapine, may be considered in patients receiving CDBCA+PEM regimen. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Chemotherapy-induced neutropenia (CIN) is a dose-limiting toxicity of many chemotherapy agents. Recently, CIN has been associated with longer survival time in various types of cancer, suggesting a role as a prognostic factor. However, no large-scale study has yet investigated the utility of CIN as a prognostic factor in small cell lung cancer. We therefore conducted this multicenter retrospective observational study to investigate the utility of CIN as a prognostic factor for overall survival (OS) in patients with extensive-disease small-cell lung cancer (ED-SCLC) treated with chemotherapy. Methods Clinical data, including data on CIN onset during chemotherapy, were collected from electronic medical records of patients with ED-SCLC who received standard-dose irinotecan and cisplatin (IP regimen) as primary therapy at 14 participating institutions across Japan between January 1, 2012 and December 31, 2016. Landmark analysis, with the association between OS and neutropenia as the primary endpoint was performed with 102 patients who completed all four cycles of the IP regimen and whose OS was ≥112 days. Univariate analysis using the log-rank test and multivariate analysis using the Cox proportional hazards model with factors previously identified as possible prognostic factors as covariates were also performed to examine the association between CIN and OS. Results Analysis of median OS by grade among patients who developed CIN revealed significantly longer survival in the group with grade 4 CIN (633 days, 95% confidence interval [CI]: 379–757) than in the group with grade 0 to 3 CIN (444 days, 95% CI: 360–505) (P = 0.0279). Multivariate analysis suggested that lactate dehydrogenase (LDH) of ≥ 230 IU/L (hazard ratio [HR]: 2.937; 95% CI: 1.739–4.958, P < 0.001) and grade 0 to 3 CIN (HR: 2.096; 95% CI: 1.151–3.818, P = 0.0156) are independent poor prognostic factors for ED-SCLC. Conclusions Onset of grade 4 CIN was associated with longer OS in patients with ED-SCLC. Our results also show that both LDH and CIN may be prognostic factors in patients treated using the IP regimen. Clinical trial identification This study was approved by the Institutional Review Board of our institution (approval no: T29-8-30-2-3). Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]