aprepitant and Dyspnea

Lung cancer is a bad prognostic illness with a limited survival and many side effects related to treatment used. Supportive care in cancer attends to enhance patient care among cancer and treatments suffering. Opioids are one of the most important treatments in the management of dyspnoea and pain. Every new drug in supportive care is tested to diminish side effects of treatment like erythropoietin against anemia or aprepitant against emesis. Many trials are developed to enhance this supportive care especially in lung cancer management.

Topics: Algorithms; Analgesics, Opioid; Angiogenesis Inhibitors; Antiemetics; Antineoplastic Agents; Aprepitant; Carcinoma, Bronchogenic; Dyspnea; Erythropoietin; Granulocyte Colony-Stimulating Factor; Humans; Lung Neoplasms; Morphine; Morpholines; Pain; Palliative Care; Prognosis; Recombinant Proteins

Evaluate safety of HTX-019, a novel polysorbate 80- and synthetic surfactant-free intravenous formulation of neurokinin 1 receptor antagonist aprepitant for chemotherapy-induced nausea and vomiting.. Two open-label, randomized, two-way crossover studies evaluated treatment-emergent adverse events (TEAEs) in 200 healthy subjects. Subjects received HTX-019 130 mg (30-min infusion) and fosaprepitant 150 mg (20- or 30-min infusion), with ≥7-day washout between doses.. Less than or equal to 30 min after start of infusion, TEAEs occurred in 5 (3%) HTX-019 and 30 (15%) fosaprepitant recipients. No HTX-019 recipients had infusion-site adverse events, versus 15 (8%) fosaprepitant recipients. Treatment-related dyspnea occurred in one HTX-019 and six fosaprepitant recipients. No severe/serious TEAEs occurred; all TEAEs resolved.. HTX-019 may provide a safer aprepitant formulation than fosaprepitant for chemotherapy-induced nausea and vomiting prevention.

Topics: Adult; Antiemetics; Antineoplastic Agents; Aprepitant; Cross-Over Studies; Dyspnea; Female; Healthy Volunteers; Humans; Infusions, Intravenous; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Treatment Outcome; Vomiting; Young Adult

The objective of this study was to investigate whether substance P, an excitatory neuropeptide, modulates the perception of breathlessness by administering aprepitant, a selective antagonist that blocks neurokinin (NK)-1 receptor signaling. Individual targeted resistive load breathing (RLB) was used to provoke breathlessness. In Study 1, sixteen patients (age, 70±6 years) with chronic obstructive pulmonary disease (COPD) reported similar ratings of breathlessness during RLB between oral aprepitant (125mg) and placebo. After aprepitant, but not with placebo, there were significant increases in blood levels of substance P (+54±39%) and beta-endorphin (+27±17%). A similar design was used in Study 2 except that naloxone (10mg) was administered intravenously prior to RLB to block any effect of endogenous opioids. Nine patients with COPD reported comparable breathlessness ratings during RLB between aprepitant and placebo. Our results do not support a role for the substance P-NK-1 pathway in the perception of breathlessness in patients with COPD. With selective antagonism of NK-1 signaling, there was co-transmission of substance P and beta-endorphin neuropeptides.

Topics: Aged; Aprepitant; beta-Endorphin; Double-Blind Method; Dyspnea; Female; Humans; Male; Morpholines; Naloxone; Narcotic Antagonists; Neurokinin-1 Receptor Antagonists; Perception; Pulmonary Disease, Chronic Obstructive; Respiration; Substance P; Time Factors; Treatment Outcome