Antiemetic Efficacy of Adding Olanzapine 5 mg to Aprepitant, Palonosetron and Dexamethasone-Sparing After Day Two for Cancer Patients Receiving Anthracycline and Cyclophosphamide.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) decrease patient quality of life (QOL). We evaluated the efficacy of adding 5 mg Olz to a three-drug steroid-sparing antiemetic regimen (aprepitant, palonosetron, and dexamethasone-sparing after day two) for breast cancer (BC) patients receiving anthracycline plus cyclophosphamide (AC) chemotherapy. PATIENTS AND METHODS: We retrospectively reviewed the records of 177 BC patients with no previous highly emetogenic chemotherapy history receiving AC plus the steroid-sparing three-drug regimen or the steroid-sparing four-drug regimen including Olz 5mg at our hospital between January 2012 and December 2018. The primary endpoint was complete response (CR), defined as no vomiting and no usage of rescue medication during the first AC cycle. We analyzed the odds ratio (OR) of the CR with 95% confidence interval (CI) in the three-drug group against the four-drug group. The OR was adjusted for types of anticancer drugs by the Cochran-Mantel-Haenszel (CMH) test. Secondary endpoints were incidences of nausea, anorexia, fatigue, and somnolence during the first cycle. RESULTS: Compared to the three-drug group, the four-drug group demonstrated high incidence of no vomiting (71% vs 95%), a similar incidence of no rescue medication usage (50% vs 51%), and a similar CR rate (45% vs 49%). The OR of the CR rate in the three-drug group against the four-drug group after CMH adjustment for drug type was 0.958 (95% CI, 0.46-1.98). Compared to the three-drug group, the four-drug group demonstrated identical incidence of nausea (66%), but lower incidences of anorexia (78% vs 35%) and fatigue (86% vs 73%). The incidence of somnolence in the four-drug group was 49%. We did not have data of somnolence for the three-drug group in the records. CONCLUSION: Adding 5 mg Olz to the steroid-sparing three-drug combination can reduce vomiting, anorexia, and fatigue, although there was no difference in CR rate.

Impact of pharmacy collaborating services in an outpatient clinic on improving adverse drug reactions in outpatient cancer chemotherapy.

BACKGROUND: Collaboration between pharmacists, doctors, and nurses in outpatient treatment is beneficial; however, such services are limited in Japan due to the lack of a healthcare reimbursement fee for outpatient pharmacy services at outpatient clinic. OBJECTIVE: We evaluated the impact of a service in which clinical pharmacists collaborated with an oncologist at an outpatient clinic in the treatment of adverse drug reactions in outpatient cancer chemotherapy. METHODS: We performed a retrospective cohort study using patients' medical records and treatment diaries. Subjects were patients who received outpatient chemotherapy via a clinical pharmacist collaboration service provided by six outpatient pharmacists and an oncologist at an outpatient clinic between June and August 2016. RESULTS: During the study period, the total number of outpatient services was 2508, with 2055 (81%) related to chemotherapy. The six outpatient pharmacists provided interventions to 498 of the 2055 cases (24%). Of the 498 interventions, 103 (20%), in addition to oncologist's prescription, were suggested treatments for adverse drug reactions due to cancer chemotherapy. Oncologists approved a total of 82 prescription suggestions from pharmacists (79%) to 63 patients. Fifty-seven percent (n = 47) of the adverse drug reactions were improved following the pharmacists' suggested prescriptions. CONCLUSIONS: This is the first study to clarify the benefits of outpatient pharmacy services in which pharmacists collaborate with oncologists at an outpatient clinic for the management of adverse drug reactions in cancer patients in Japan.

Retrospective analysis of premedication, glucocorticosteroids, and H1-antihistamines for preventing infusion reactions associated with cetuximab treatment of patients with head and neck cancer.

Objectives We evaluated infusion-related reactions associated with cetuximab combination chemotherapy comprising an H1-receptor antagonist plus dexamethasone as anti-allergy premedications for patients with head and neck cancer. Methods We retrospectively evaluated 248 patients who received a cetuximab combination regimen between December 2012 and August 2015. All patients received 5 mg intravenous dichlorpheniramine (H1-receptor antagonist), and dexamethasone (DEX) was adjusted from 6.6 mg to 13.2 mg according to the emetogenic risk. Results We identified 248 subjects, including 13 (5.2%) with infusion-related reactions (grade 1 in five [2.0%], grade 2 in seven [2.8%], and grade 4 in one [0.4%]). The incidence of these reactions in cetuximab combination regimens, each employing an H1-receptor antagonist, using a higher dose of dexamethasone (13.2 mg) was not significantly lower compared with those using 6.6 mg DEX (2.4% vs 8.3%, respectively; p = 0.43). Twelve patients experienced infusion-related reactions associated with the first cetuximab administration, and one reaction occurred after the third administration. Conclusions The incidence of infusion-related reactions was lower compared with those of previous studies. Dexamethasone combined with an H1-receptor antagonist was useful for preventing allergic responses. The incidence of infusion-related reactions was not lower with 13.2 mg dexamethasone, and 6.6 mg DEX prevented infusion-related reactions.

Evaluation of the anticoagulant effect and timing of the concomitant use of S-1 and warfarin.

Objectives To evaluate the effects of the timing of warfarin (WF) administration in patients with gastric cancer who received S-1 oral chemotherapy. Methods This retrospective chart review collected patient data including the prothrombin time international normalized ratio (PT-INR). Patients were categorized into three groups based on the timing of WF administration in relation to S-1 oral chemotherapy: group A patients received WF before S-1 chemotherapy; group B patients started WF during S-1 chemotherapy; and group C patients started WF after completing S-1 chemotherapy. Results A total of 21 patients with gastric cancer were included in the study; group A ( n = 8), group B ( n = 10) and group C ( n = 3). Seven patients (88%) in group A, seven (70%) in group B and all of the patients (100%) in group C had >2.5 PT-INR. There was no significant difference in the time-to-exceed 2.5 PT-INR between groups A and B. Conclusions These findings suggest that the timing of WF use in relation to S-1 chemotherapy might not be an important factor for PT-INR, although the low patient numbers included in the study should be taken into consideration.

[Evaluation of Drug Interaction between S-1 and Warfarin].

Prolonged prothrombin time is observed in patients taking warfarin (WF) with a fluoropyrimidine, such as S-1. When WF is combined with S-1, the prothrombin time-international normalized ratio (PT-INR) and dose adjustment of WF should be closely monitored. To date, no clinical data have been reported in terms of the relation between temporal variation of PT-INR and its therapeutic range. In this study, we retrospectively collected patients' clinical data including PT-INR. We identified 21 patients receiving WF therapy before the start of S-1 treatment. Patient characteristics were male/female: 18/3, median age: 69 (range 48-81) years old, cancer of gastric/lung/pancreatic/other: 8/5/4/4, and history of deep vein thrombosis (DVT)/atrial fibrillation (AF)/cerebral infarction (CI)/other: 11/6/2/2. The PT-INR of 16 patients exceeded normal upper limits after taking S-1 with WF. The median time to exceed the PT-INR upper therapeutic range is 25 (range 3-77) days. Patients receiving WF anticoagulant therapy concomitant with S-1 should have their PT-INR closely monitored and WF doses adjusted accordingly.