Resistance to antiemetic treatment with 5-hydroxytryptamine-3 receptor antagonist is an issue. This study evaluated the potential roles of ABCB1 and ABCG2 polymorphisms in antiemetic treatment resistance in patients with cancer previously enrolled in a randomized controlled trial. A total of 156 patients were evaluated for their responses to antiemetic therapy and then subdivided into granisetron or palonosetron groups. The genotypes were evaluated for their association with antiemetic efficacy in each treatment groups. Additional risk factors associated with complete response (CR) were examined using a multivariate regression analysis. No significant associations were identified for genetic polymorphisms in the palonosetron group. In the granisetron group, patients with ABCB1 2677TT and 3435TT genotypes had higher proportion of CR. In addition to ABCB1 polymorphisms, gender and cisplatin dose were associated with granisetron response by univariate analysis. Multivariate logistic regression analysis revealed that the ABCB1 3435C>T polymorphism and cisplatin dose were significant predictors of CR.

Interindividual differences in the clinical effects of 5-HT(3) receptor antagonists could be evaluated based on receptor occupancy theory, and the differences varied among drugs. Drug selection considering these individual variations might be useful for the patients who experienced vomiting associated with chemotherapy.

Clinical trial information: UMIN 000009335.

Chemotherapy-induced neutropenia (CIN) is a dose-limiting factor for cytotoxic chemotherapy, but recently, it was suggested that CIN contributes to prolonged survival. In this study, we examined the association between severe CIN and survival, and determined whether CIN affected survival in patients with extensive-stage small cell lung cancer (ED-SCLC).The medical records from 214 patients with ED-SCLC treated with etoposide or irinotecan in combination with cisplatin (EP/IP) between 2012 and 2016 were collected and retrospectively analyzed. Landmark analysis was performed at the end of cycle 4 and the relationship between severe CIN and survival was determined by a log-rank test. In addition, a multivariate analysis using COX proportional hazard model was performed to identify independent predictive factors. The Landmark analysis included 102 patients in the IP-group and 47 patients in the EP-group. No significant difference was found between grade 0–3 and grade 4 neutropenia and overall survival (OS) in the EP-group. (P = 0.57). Contrariwise, for the IP patients, the median OS was 444 days for grade 0–3 and 633 days for grade 4 neutropenia, which was significantly longer for patients who developed grade 4 neutropenia (P = 0.03). Multivariate analysis adjusted for potential factors revealed that the development of grade 4 CIN was identified as a significant predictor of longer OS (hazard ratio [HR], 0.46; 95% confidence interval (CI), 0.26–0.81, P = 0.008). The results indicated that the development of severe CIN with IP therapy is associated with prolonged OS.

No abstract