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Conference News
Palonosetron Reduces Readmissions for CINV in Patients Receiving IP Cisplatin NEW ORLEANS—A retrospective analysis of healthcare resource utilization for patients with ovarian cancer receiving intraperitoneal (IP) cisplatin chemotherapy identified a trend toward more hospital readmissions for chemotherapy-induced nausea and vomiting (CINV) among patients receiving ondansetron prophylaxis, as compared with palonosetron. The study from Brigham and Women’s Hospital (BWH) in Boston was presented by Ann McDonnell, PharmD, BCOP. Palonosetron was identified as a highexpenditure drug by the Partners HealthCare System Center for Drug Policy, a center established by BWH’s integrated healthcare system to study the effectiveness of new drugs before or as they are being introduced to the market. An evaluation of prior medication use identified the gynecologic oncology group as the predominant prescriber of palonosetron at BWH, frequently for patients receiving IP cisplatin. Palonosetron and ondansetron are the two 5-hydroxytryptamine-3 (5HT3) receptor antagonists included on the BWH formulary. A literature review concluded that these agents can be considered clinically interchangeable (Yeh YV, et al. J Oncol Pharm Pract. May 7, 2010. Epub ahead of print), but the cost of generic ondansetron is severalfold lower than that of palonosetron, McDonnell pointed out. In March 2008, BWH instituted protocol guidelines that consisted of ondansetron for first-line use and palonosetron for second-line use (Table). “When ondansetron became generic, the differences in cost became substantial. We changed practice to use ondansetron first-line, but anecdotal reports from our healthcare providers suggested that patients who receive ondansetron were more likely to have additional healthcare resource use due to CINV,” she said. The study aimed, therefore, to describe the use of these agents in patients receiving IP cisplatin and to compare the two agents with regard to resource utilization. The investigators reviewed medical records during three time periods: two periods prior to BWH guidelines (January through June 2006 for ondansetron and October 2007 through June 2008 for palonosetron) and one period after guideline implementation for ondansetron (March through June 2008). The occurrence of CINV-related hospital readmissions, emergency depart-
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Table. Dosing Regimens Used at Brigham and Women’s Hospital Ondansetron Group
Palonosetron Group
Day 2
Aprepitant 125 mg, oral Dexamethasone 12 mg, IV Ondansetron 24 mg, oral or IV
Aprepitant 125 mg, oral Dexamethasone 12 mg, IV Palonosetron 0.24 mg, IV
Day 3
Aprepitant 80 mg, oral Dexamethasone 12 mg, IV Ondansetron 24 mg, oral or IV
Aprepitant 80 mg, oral Dexamethasone 12 mg, IV
Day 4
Aprepitant 80 mg, oral Dexamethasone 12 mg, oral
Aprepitant 80 mg, oral Dexamethasone 12 mg, oral
ment visits, and outpatient encounters (ie, clinic visits, telephone calls) within 7 days after cisplatin administration was compared. Reasons for healthcare resource use were determined by reviewing medical charts. CINV-related resource use was defined as events associated with dehydration due to nausea and vomiting, hypovolemia, hypokalemia, constipation, shortness of breath, or syncope/collapse. Trend toward increased readmissions with ondansetron Hospital readmissions tended to be greater with ondansetron: 2/39 (5.1%) patients, both CINV related, compared with 2/89 (2.3%), neither of which was CINV related (P = .09 for CINV-related admissions). One of the readmitted patients had documented electrolyte imbalance, nausea and vomiting, and dehydration on day 7 of the chemotherapy cycle. This patient received oral ondansetron only on the day of IP cisplatin during her hospital stay. The other readmitted patient received intravenous ondansetron for 2 days and reported dehydration 4 days after IP cisplatin. There were no CINV-related emergency department visits. CINV-related outpatient visits were documented in four (10.3%) patients receiving ondansetron and seven (7.9%) patients receiving palonosetron (P = .657). Twice as many of the ondansetron group patients (5.1% vs 2.3%) switched to the alternate 5-HT3 receptor antagonist. “To our knowledge this is the first realworld comparison of healthcare resource use between patients given ondansetron or palonosetron for prophylaxis of CINV,” McDonnell said. “Our analysis found a trend toward a higher incidence of CINV-related hospital readmissions with ondansetron, though not statistically significant, which is consistent with clinicians’ anecdotal reports.” These findings need to be confirmed in prospective, randomized trials that
Palonosetron uniquely inhibits neurokinin-1 agonist responses in vitro and in vivo. compare outcomes with single-dose palonosetron versus multiday ondansetron therapies in the IP cisplatin population, she said. She noted that the dosing of ondansetron might have been suboptimal in some cases; 27% of patients in this study received only 1 day of ondansetron during their hospital stay. During the discussion, it was noted that the dose of cisplatin that many patients were given (100 mg/m2) is now viewed as unacceptably high. Regardless, McDonnell emphasized that oncologists at BWH were unhappy with ondansetron. “It is a challenge to get our physicians to accept ondansetron for patients receiving IP cisplatin,” she said. Palonosetron inhibits NK1 agonist responses In a second presentation, Barbara Slusher, PhD, chief scientific officer for the Johns Hopkins Brain Science Institute NeuroTranslational Program,
Baltimore, reported results of translational work showing that palonosetron uniquely inhibits neurokinin-1 (NK1) agonist responses in vitro and in vivo. The same was not found for ondansetron or granisetron. Previous work has shown that palonosetron exhibits allosteric binding and positive cooperativity (Rojas C, et al. Anesth Analg. 2008;107:469-478) and triggers receptor internalization and prolonged inhibition of receptor function (Rojas C, et al. Eur J Pharmacol. 2010; 626:193-199). NK1 receptor antagonists are used to prevent delayed emesis. Palonosetron helps prevent delayed emesis as well. Slusher and her colleagues investigated whether palonosetron indirectly antagonizes the NK1 pathway. “Our results provide a rationale for the efficacy observed with palonosetron in delayed emesis in the clinic,” Slusher said. ● —CH
Changes Ahead with Healthcare Reform... Continued from page 8 if CER findings are tied to provider incentives, he added. The fiscal year 2011 budget is likely to include additional funding for CER. The Agency for Healthcare Research and Quality will be budgeted approximately $286 million, which is an increase of $261 million over fiscal year 2010. The Senate Finance Committee proposal recommends that CER be governed by a nonprofit entity with a public/private board. It proposes long-term funding from private insurers and a Medicare trust fund on a per-member basis.
Language was added to ensure that CER not be used as the sole basis for Medicare coverage decisions. Coverage determinations must give weight to all relevant studies and evidence, and to evidence suggestive of benefits to specific subpopulations, “even if, on average, no such benefit is seen,” he said. “I think this will change over time, however, as experience widens with CER and more become involved,” he predicted. “Our view is that oncology needs to be part of the decision-making process in CER.” ●
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