The efficacy and safety of the addition of olanzapine to ondansetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy.

OBJECTIVE: To evaluate the efficacy and safety of the addition of olanzapine to ondansetron and dexamethasone for chemotherapy-induced nausea vomiting (CINV) prevention in patients receiving highly emetogenic chemotherapy (HEC). METHODS: In this randomized, double-blind, placebo-controlled, crossover study, we randomly assigned chemotherapy-naïve patients receiving HEC to receive olanzapine or placebo in addition to ondansetron and dexamethasone. All subjects were crossed over to another treatment arm on second-cycle chemotherapy. The primary endpoint was complete response (CR) rate defined as no vomiting and no use of rescue drugs. RESULTS: At the first cycle, there were significantly more patients with CR in the olanzapine group than in the placebo group in overall phase (68.7% vs. 25.0%, p < 0.001), acute phase (0-24 h) (75.0% vs. 31.2%, p < 0.001) and delayed phase (24-120 h) (68.7% vs. 43.7%, p = 0.038). After crossover, there were significantly more patients with CR in the olanzapine group than in the placebo group in overall phase (67.2% vs. 25.0%, p < 0.001), acute phase (71.9% vs. 32.8%, p < 0.001) and delayed phase (67.2% vs. 37.5%, p < 0.001). In crossover analysis, the olanzapine group had significantly lower mean nausea (1.28 vs. 3.05, p < 0.001) and fatigue (3.5 vs. 4.58, p < 0.001) scores but higher mean appetite (2.5 vs. 1.55, p = 0.003) and sleepiness (3.26 vs. 2.2, p < 0.001) scores. There were no grade 3 and 4 anti-emetic-drug-related toxicities. Mean QT interval changes did not different between two groups (-4.30 vs. -1.86, p = 0.69). CONCLUSION: The addition of olanzapine to ondansetron and dexamethasone significantly improved CINV prevention and was safe in patients receiving HEC.

Incidence of infusion hypersensitivity reaction after withholding dexamethasone premedication in early breast cancer patients not experiencing two previous cycles of infusion hypersensitivity reaction for weekly paclitaxel chemotherapy.

BACKGROUND: Premedication with dexamethasone is an essential part of the prevention of hypersensitivity reaction (HSR) associated with taxane administration. However, the possibility of stopping dexamethasone premedication has been investigated in previous studies to reduce the steroid's adverse events; however, either the result or the particular protocol was limited. Thus, our study aimed to evaluate the incidence of HSR after dexamethasone premedication discontinuation after lack of HSR in two previous weekly paclitaxel infusions. METHOD: Early breast cancer patients who received adjuvant weekly paclitaxel in a retrospective cohort from January 2012 through February 2016 at the King Chulalongkorn Memorial Hospital were reviewed. All patients received a standard premedication protocol prior to the first and second paclitaxel infusion. Dexamethasone was omitted in later cycles in all patients who did not undergo infusion HSR. Patients who developed HSR during the first or second cycles of paclitaxel infusion were excluded. The incidence of HSR during the later cycle of paclitaxel administration and factors associated with this adverse reaction were collected. RESULTS: Eighty-one of 85 patients who did not undergo infusion HSR after 2 cycles of weekly paclitaxel administration were retrospectively reviewed. The median age was 51 years (range 27-74 years). Only 16% of the patients had a BMI greater than 30 kg/m2, 57.8% were premenopausal, 67.9% had no comorbidity, none had a history of allergy or asthma, 65.4% received weekly paclitaxel as a single agent, and 34.6% received weekly paclitaxel in combination with trastuzumab. Five of 81 patients reported grade I-II HSR (6.25%), which occurred mostly during the first 6 cycles (60%). Temporary discontinuation of paclitaxel infusion was observed in all HSR patients. No differences regarding age, BMI, menopausal status, and underlying disease between the HSR and no HSR groups were identified. Concerning the safety profile, peripheral neuropathy (gr I 60%, gr II 13.5%, and gr III 2.4%), myalgia (43.4%), and edema (10.5%) were commonly reported, whereas dyspepsia (5.3%) and insomnia (14.5%) were rarely described in withholding patients. CONCLUSION: Withholding dexamethasone premedication in non-experiencing HSR patients after two previous cycles of weekly paclitaxel administration was safe and did not impact the higher incidence of HSR. A discontinuing dexamethasone protocol should be recommended generally in these patients, especially those with a high risk for steroid-induced side effects.

Lactic acidosis, a potential toxicity from drug-drug interaction related to concomitant ribociclib and metformin in preexisting renal insufficiency: A case report.

BACKGROUND: Ribociclib, one of the cyclin-dependent kinases (CDK) 4 and 6 inhibitors, in combination with endocrine therapies has been approved in the treatment of hormonal receptor positive, HER-2 negative metastatic breast cancer worldwide. Long-term usage of ribociclib with concomitant drugs, potential drug-drug interaction may develop which can limit the therapeutic value of CDK4/6 inhibitor. CASE: A 62-year-old with history of non-insulin dependent diabetic, dyslipidemia, and essential hypertension was diagnosed with HR-positive, HER-2 negative metastatic breast cancer and treated with fulvestrant plus ribociclib. Four weeks after administration, elevated serum creatinine was observed, and then severe lactic acidosis with acute respiratory failure was subsequently reported. Ribociclib and fulvestrant were temporarily discontinued. Three days after renal replacement therapy, her clinical was stabilized. Combination ribociclib with metformin resulted in high plasma metformin levels and dangerous consequences. Hence, special precaution should be considered during concomitant treatment with sensitive transporter substrates. CONCLUSION: Metformin associated lactic acidosis may potentially occur after combination with ribocilib, an uncommon but lethal complication from the interaction of these drugs, especially in patients who had preexisting renal impairment.

Immunogenicity of ChAdOx1-nCoV-19 vaccine in solid malignancy patients by treatment regimen versus healthy controls: A prospective, multicenter observational study.

Background: Limited data exists regarding the efficacy of ChAdOx1-nCoV-19 vaccine against Severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) in solid cancer patients. We aimed to assess the immunogenicity of the ChAdOx1-nCoV-19 vaccine and the impact of different anticancer therapies for solid malignancies on immune response. Methods: This prospective, longitudinal observational study of immunogenicity following ChAdOx1-nCoV-19 vaccination among 385 solid cancer patients on active cancer treatment was conducted in two oncology centers. Participants received the first dose between June 18 and July 27, 2021 and the second dose at 8-10 weeks later. Blood samples were evaluated for total immunoglobulins against the receptor-binding of SARS-CoV-2 spike protein (anti-RBD total-Ig) before, and 4-week after the first- and second-doses. The primary endpoint was the geometric mean titers (GMT) of antibody among solid cancer patients compared to healthy controls and the impact of different cancer treatment types. Findings: Among solid cancer patients, the antibody level increased more slowly to significantly lower levels than achieved in healthy controls. The GMT at 4-weeks post-vaccination in cancer vs. healthy were 224.5 U/ml (95%CI 176.4-285.6) vs. 877.1 U/ml (95%CI 763.5-1008), p<0.0001), respectively. For different types of cancer treatments, chemotherapy agents, especially anthracyclines (GMR 0.004; 95%CI 0.002-0.008), paclitaxel (GMR 0.268; 95%CI 0.123-0.581), oxaliplatin (GMR 0.340; 95%CI 0.165-0.484), and immunotherapy (GMR 0.203; 95%CI 0.109-0.381) showed significantly lower antibody response. Anti-HER2, endocrine therapy and 5-fluouracil or gemcitabine, however, had less impact on the immune response. Interpretation: Suboptimal and heterogeneous immunologic responses were observed in cancer patients being treated with different systemic treatments. Immunotherapy or chemotherapy significantly suppressed the antibody response. Funding: Quality Improvement Fund, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society and Center of Excellence in Clinical Virology at Chulalongkorn University and Chulalongkorn Medical Oncology Research Fund.