MCO 2011 - Slide 11 - M. Aapro - Antiemetics, growth factors, bone health

Editor's Notes

• #24: Slide 9 In a prospective survey study, 80 patients from 6 oncology practices received a 5-HT 3 receptor antagonist with 84% also receiving a corticosteroid prior to receipt of chemotherapy (90% received moderately emetogenic regimens). Physicians and nurses consistently overestimated the efficacy of antiemetic treatment. The greatest discrepancy between predicted and actual nausea and emesis occurred for the delayed period, with physicians and nurses underestimating the presence of nausea/vomiting by approximately 30%. Of interest, even with treatment with a 5-HT 3 receptor antagonist, 47% of patients experienced acute nausea and 57% experienced delayed nausea. 1 1. Grunberg SM, Hansen M, Deuson R et al. Incidence and impact of nausea/vomiting with modern antiemetics: perception vs. reality. Proc Am Soc Clin Oncol. 2002:21(part 1);250a. Abstract #996.
• #25: Multiple neurotransmitters are involved in emesis. Three 5-HT3 receptor antagonists were approved for use in the United States for chemotherapy-induced emesis prior to the approval of palonosetron (Aloxi®): ondansetron (Zofran®), dolasetron (Anzemet®), and granisetron (Kytril®). 5-HT3 antagonists are first-line treatments for emesis associated with chemotherapy.1 Prior to the use of 5-HT3 receptor antagonists, dopamine antagonists (especially metoclopramide) were used to treat emesis from highly emetogenic chemotherapy regimens. Use of dopamine antagonists is limited by antidopaminergic side effects,2 including extrapyramidal reactions, anxiety, and depression. The effectiveness of metoclopramide, which is due to both antidopaminergic and antiserotonergic actions, led to the development of 5-HT3 receptor antagonists specifically for the treatment of emesis.2 Cannabinoids are effective in patients receiving moderately emetogenic chemotherapy, although serious side effects (including dysphoria, hallucinations, sedation, and disorientation) limit their use.2 A relatively new treatment option are the NK-1 antagonists, with aprepitant as the only agent in this class with FDA approval. As single agents, NK-1 antagonists are less effective than serotonin receptor antagonists in preventing acute emesis. However, when combined with serotonin receptor antagonists, they appear to be effective in delayed emesis.3 Gralla RJ, Osoba D, Kris MG et al. Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines. J Clin Oncol. 1999;17:2971-2994. 2. Grunberg SM, Hesketh PJ. Control of chemotherapy-induced emesis. N Engl J Med. 1993;329: 1790-1796. 3. Hesketh PJ. Potential role of NK1 receptor antagonists in chemotherapy-induced nausea and vomiting. Support Care Cancer . 2001;9:350-354.
• #30: Emend is a moderate CYP3A4 inhibitor and should not be used concurrently with pimozide, terfenadine, astemizole, or cisapride.Inhibition of cytochrome CYP450 isoenzyme 3A4 by aprepitant could result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions. Due to the small number of patients in clinical studies who received the CYP3A4 substrates docetaxel, vinblastine, vincristine, or ifosfamide, particular caution and careful monitoring are advised in patients receiving these agents or other chemotherapy agents metabolized primarily by CYP3A4 that were not studied. Coadministration of Emend with warfarin may result in a clinically significant decrease in INR or prothrombin time. In patients on chronic warfarin therapy, the INR should be closely monitored in the 2-week period, particularly at 7 to 10 days, following initiation of the 3-day regimen of Emend with each chemotherapy cycle. Oral dexamethasone doses should be reduced by approximately 50% when coadministered with Emend, to achieve exposures of dexamethasone similar to those obtained when it is given without Emend. Reference 1. Emend ® (aprepitant) [package insert]. Whitehouse Station, NJ; Merck & Co, Inc: March 2003.
• #34: ITT populationP value comparing two groups calculated by one-sided Cochran-Mantel-Haenszel test stratifed by centres P values P overall 0.478 Acute 0.573 Delayed 0.250
• #35: Overall p 0.429 Acute 0.583 Delayed 0.077
• #53: Currently, guidance is emerging for women with early-stage breast cancer receiving aromatase inhibitor (AI) therapy A recent publication by Moy et al (2007) recommends Treatment for patients with T-score < –2.0 Consideration of bisphosphonate therapy for patients with T-score –1.5 to –2.0 (osteopenic) based on additional risk factors Annual bone mineral density (BMD) screening for patients with T-score –1.0 to –1.5 A recent abstract by Aapro et al (2007) Presented a literature review study to identify factors contributing the increased fracture risk Using an evidence-based medicine approach, among patients with breast cancer, risk factors were assessed to identify patients who may benefit from bisphosphonate therapy Risk assessments were recommended for patients with or without BMD T-scores