A multicenter phase II trial of the triplet antiemetic therapy with palonosetron, aprepitant, and olanzapine for a cisplatin-containing regimen. - PATROL-I.

Dexamethasone is one of the key antiemetic agents and is widely used even now. However, dexamethasone has been associated with several adverse reactions even after short-term administration. Therefore, developing a steroid-free antiemetic regimen is an important issue to consider. Thus, the purpose of this study was to investigate the efficacy and safety of palonosetron, aprepitant, and olanzapine in a multi-institutional phase II study. Chemotherapy-naive patients scheduled to receive cisplatin were enrolled and evaluated for the occurrence of chemotherapy-induced nausea and vomiting during 120 h after chemotherapy. The primary endpoint of the study was total control (TC) in the overall phase. The key secondary endpoint was complete response (CR), which was assessed in the acute, delayed, and overall phase, respectively. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events. Eighty-five patients were enrolled from 8 centers in Japan, of which 83 were evaluable for analyses. The percentage of patients who achieved TC during the overall phase was 31.3%. CR was achieved in 61.4%, 84.3%, and 65.1% of patients during the overall, acute, and delayed phases, respectively. The most frequently reported adverse event was anorexia. The primary endpoint was below the threshold and we could not find benefit in the dexamethasone-free regimen, but CR during the overall phase was similar to that of the conventional three-drug regimen. This antiemetic regimen without dexamethasone might be an option for patients for whom corticosteroids should not be an active application.

Chemotherapy-induced neutropenia as a prognostic factor in patients with extensive-stage small cell lung cancer.

PURPOSE: 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 (ES-SCLC). METHODS: The medical records from 214 patients with ES-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 the 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. RESULTS: No significant difference was found between grades 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 grades 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], 0.50; 95% confidence interval (CI), 0.28-0.87, P = 0.015). CONCLUSION: The results indicated that the development of severe CIN with IP therapy is associated with prolonged OS.

A retrospective study comparing interventions by oncology and non-oncology pharmacists in outpatient chemotherapy.

BACKGROUND: The differences in the clinical pharmacy services (CPS) provided by oncology and non-oncology pharmacists have not been sufficiently explained. AIM: This study aimed to demonstrate the differences in direct CPS provided by oncology and non-oncology pharmacists for patients and physicians, and to assess the potential impact of these services on medical costs. METHODS: We retrospectively examined CPS provided by oncology and non-oncology pharmacists for outpatients who underwent chemotherapy between January and December 2016. RESULTS: In total, 1177 and 1050 CPS provided by oncology and non-oncology pharmacists, respectively, were investigated. The rates of interventions performed by oncology and non-oncology pharmacists for physicians-determined treatment were 18.5% and 11.3%, respectively (p < .001). The rates of oncology and non-oncology pharmacist interventions accepted by physicians were 84.6 and 78.8%, respectively (p = .12). Level 4 and Level 5 interventions accounted for 64.6% of all oncology pharmacist interventions and 53.0% of all non-oncology pharmacist interventions (p = .03). The rates of improvement in symptoms from adverse drug reactions among patients resulting from interventions by oncology and non-oncology pharmacists were 89.4 and 72.1%, respectively (p = .02). Conservative assessments of medical cost impact showed that a single intervention by an oncology and by a non-oncology pharmacist saved ¥6355 and ¥3604, respectively. CONCLUSION: The results of the present study suggested that CPS by oncology pharmacists enable safer and more effective therapy for patients with cancer and indirectly contribute to reducing health care fees.

Comparative trial of two intravenous doses of granisetron (1 versus 3 mg) in the prevention of chemotherapy-induced acute emesis: a double-blind, randomized, non-inferiority trial.

PURPOSE: A single 3 mg or 40 µg/kg intravenous dose of granisetron combined with dexamethasone is routinely used in several countries, although the antiemetic guidelines have recommended granisetron at the dose of 1 mg or 10 µg/kg. A randomized, multicenter trial was conducted to determine the optimal intravenous granisetron dose, 1 or 3 mg, in cancer patients receiving emetogenic chemotherapy. METHODS: We enrolled 365 patients and randomly assigned them to receive intravenous granisetron 3 mg (3-mg group) or 1 mg (1-mg group), combined with dexamethasone at an adequate dose fixed as per the emetic risk category. The primary end point was the proportion of patients with a complete response during the first 24 h after chemotherapy. RESULTS: The study demonstrated that 1 mg of granisetron was not inferior in effect to 3 mg. For the primary end point, 359 patients were evaluable according to the modified intention-to-treat (ITT) analysis. Complete protection was achieved in the modified ITT population, 90.6% and 88.8% for the 3- and 1-mg groups, respectively (p < 0.01 for non-inferiority). CONCLUSIONS: This study showed that 1 mg granisetron is not inferior to 3 mg when both doses are combined with dexamethasone. Therefore, 1-mg dose of intravenous granisetron should be the recommended prophylactic regimen for the prevention of acute emesis.

[Safety analysis of eight patients treated with erlotinib after severe gefitinib-induced liver injury].

Gefitinib and erlotinib are commercially available epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) that are widely used for the treatment of non-small-cell lung cancer (NSCLC). Acute severe liver injury, although rare, has been observed in patients receiving these EGFR-TKIs. Some studies have reported that erlotinib treatment does not cause severe liver toxicity in patients with NSCLC who previously presented with severe liver injury during the course of gefitinib treatment. We retrospectively assessed the occurrence of liver toxicity in patients with NSCLC who were receiving erlotinib and had previously presented with severe gefitinib-induced liver injury.Severe liver injury occurred in only 1 of the 8 patients receiving erlotinib treatment. In this case, erlotinib was discontinued because of the onset of grade 3 skin rash and liver injury. After liver function was restored, erlotinib (100 mg) was administered at a lower dose; nonetheless, grade 4 liver injury occurred. Our findings suggest that it is necessary not only to explain the early symptoms of liver toxicity to patients who are receiving erlotinib treatment and have previously experienced gefitinib-induced severe liver injury but also to more closely monitor liver function.

[Revision of the informed consent form for patients based on investigation of adverse events of mFOLFOX6 regimen].

We retrospectively investigated the frequency and severity of adverse events in 124 patients with colorectal cancer who were treated by mFOLFOX6 regimen from August, 2005 to December, 2006. The incidences of grade 3/4 adverse events were; leucopenia 16%, neutropenia 40%, anemia 11%, thrombocytopenia 7%, febrile neutropenia 7%, nausea 3%, vomiting 2%, anorexia 2%, diarrhea 4%, fatigue 7%, and alopecia 0%. The incidences of all grades and grade 3/4 hypersensitivity reaction were 35% and 4%, and the median number of course when it firstly appeared was 6(range, 1-21). The incidences of all grade and grade 3 peripheral sensory neuropathy were 74% and 6%, and the median number of course when it firstly appeared 11(range, 6-16). The incidences of adverse events in this cohort were similar or lower than those reported in Western countries. Our investigation shows that mFOLFOX6 regimen is tolerable in clinical practice in Japan. The informed consent form was revised based on these results. The incidences of adverse events were renewed to provide useful information and improve self-care ability. The symptoms and the time to appearance of the hypersensitivity reaction and peripheral sensory neuropathy were added. We think it is important to provide the information based on the clinical practice.