Combination of aprepitant, palonosetron and dexamethasone as antiemetic prophylaxis in lung cancer patients receiving multiple cycles of cisplatin-based chemotherapy

F Longo, G Mansueto, V Lapadula, L Stumbo, G Del Bene, D Adua, L De Filippis, E Bonizzoni, S Quadrini, F Longo, G Mansueto, V Lapadula, L Stumbo, G Del Bene, D Adua, L De Filippis, E Bonizzoni, S Quadrini

Abstract

Introduction: With repeated courses of chemotherapy, chemotherapy-induced nausea and vomiting (CINV) becomes progressively more difficult to control. The aim of this study was to evaluate whether the antiemetic efficacy of the triple combination aprepitant, palonosetron and dexamethasone could be sustained for up to six cycles of highly emetogenic chemotherapy (HEC) (cisplatin ≥ 50 mg/m(2) ). Methods: Chemotherapy-naive patients receiving cisplatin-based HEC, were treated with palonosetron 0.25 mg/i.v., dexamethasone 20 mg/i.v. and aprepitant 125 mg/p.o. 1 h before chemotherapy. Aprepitant 80 mg/p.o. and dexamethasone 4 mg/p.o. were administered on days 2-3. The primary endpoint was complete response (CR, no vomiting and no use of rescue medication), over 5 days following HEC in up to six cycles. Secondary endpoints were emesis-free and nausea-free rates. Safety was also evaluated. Results: One hundred and fifty six lung cancer patients were included in the study; the median age was 64 years and 76.9% were men. The minimum cisplatin dosage was 75 mg/m(2) , and in most patients was combined with another drug (87.4%). CR ranged from 74.4% (first cycle) to 82% (sixth cycle). More than 90% and 60% of patients were emesis-free and nausea-free during all chemotherapy cycles. The most commonly reported side effects were constipation and headache. Conclusions: The triple combination of aprepitant, palonosetron and dexamethasone enhanced not only the antiemetic protection during the first cycle, but its efficacy was also sustained for up to six cycles of cisplatin-based HEC in lung cancer patients.

© 2012 Blackwell Publishing Ltd.

Figures

Figure 1
Figure 1
Complete response rate with 95% CI. Complete response is defined as no emesis and no use of rescue medication
Figure 2
Figure 2
Complete control rate with 95% CI. Complete control is defined as no emesis, no use of rescue medication and no more than mild nausea experience

References

    1. Jemal A, Siegel R, Ward E, et al. Cancer Statistic, 2009. CA Cancer J Clin. 2009;59:225–49.
    1. Dong X, Huang J, Cao R, et al. Palonosetron for prevention of acute and delayed nausea and vomiting in non-small-cell lung carcinoma patients. Med Oncol. 2010;28(4):1425–9.
    1. Feinberg B, Gilmore J, Haislip S, et al. Impact of initiating antiemetic prophylaxis with palonosetron versus ondansetron on risk of uncontrolled chemotherapy-induced nausea and vomiting in patients with lung cancer receiving multi-day chemotherapy. Sup Care Cancer. 2012;20:615–23.
    1. Roila F, Herrstedt J, Aapro M, et al. Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol. 2010;21(Suppl 5):v232–43.
    1. Basch E, Prestrud AA, Hesketh PJ, et al. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2011;29(31):4189–98.
    1. Hesketh PJ. Defining the emetogenicity of cancer chemotherapy regimens: relevance to clinical practice. Oncologist. 1999;4:191–6.
    1. Rubenstein EB. Costs and benefits of outpatient therapy. Sup Care Cancer. 1994;2(5):307–11.
    1. Eisenberg P, Figuero-Vadillo J, Zamora R, et al. 99-04 Palonosetron Study Group. Improved prevention of moderately emetogenic chemotherapy induced nausea and vomiting with palonosetron, a pharmacologically novel 5HT3 receptor antagonist. Results of a phase III, single dose trial versus dolasetron. Cancer. 2003;98(11):2473–82.
    1. Gralla R, Lichinitser M, Van Der Vegt S, et al. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol. 2003;14:1570–7.
    1. Aapro MS, Grunberg SM, Manikhas GM, et al. A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy. Ann Oncol. 2006;17(9):1441–9.
    1. Rubenstein EB, Gralla RJ, Eisenberg P, et al. Palonosetron (PALO) compared with ondansetron (OND) or dolasetron (DOL) for prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Combined results of two Phase III trials. Proc Am Soc Clin Oncol. 2003;22:729.
    1. Saito M, Aogi K, Sekine I, et al. Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial. Lancet Oncol. 2009;10(2):115–24.
    1. Hesketh PJ, Grunberg SM, Gralla RJ, et al. The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomised, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin: the aprepitant protocol 052 study group. J Clin Oncol. 2003;21(22):4112–9.
    1. Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, et al. Addition of the neurokinin 1 receptor anatagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting: results from a randomized, double-blind, placebo-controlled trial in Latin America. Cancer. 2003;97(12):3090–8.
    1. Schmoll HJ, Aapro MS, Poli-Bigelli S, et al. Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment. Ann Oncol. 2006;17(6):1000–6.
    1. Italian Group for Antiemetic Research. Double-blind, dose-finding study of four intravenous doses of dexamethasone in the prevention of cisplatin-induced acute emesis. J Clin Oncol. 1998;16:2937–42.
    1. Grunberg SM. Antiemetic activity of corticosteroids in patients receiving cancer chemotherapy: dosing, efficacy, and tolerability analysis. Ann Oncol. 2007;18:233–40.
    1. Grunberg S, Clark-Snow RA, Koeller J. Chemotherapy-induced nausea and vomiting: contemporary approaches to optimal management: Proceedings from a symposium at the 2008 Multinational Association of Supportive Care in Cancer (MASCC) Annual Meeting. Sup Care Cancer. 2010;18(Suppl 1):1–10. PMID 20084406.
    1. Schwartzberg L, Jackson J, Jain G, et al. Impact of 5-HT(3) RA selection within triple antiemetic regimens on uncontrolled highly emetogenic chemotherapy-induced nausea/vomiting. Expert Rev Pharmacoecon Outcomes Res. 2011;11(4):481–8.
    1. De Wit R, Van Den Berg H, Burghouts J, et al. Initial high anti-emetic efficacy of granisetron with dexamethasone is not maintained over repeated cycles. Br J Cancer. 1998;77(9):1487–91.
    1. De Wit R, Herrstedt J, Rapoport B, et al. Addition of the oral NK 1 antagonist aprepitant to standard antiemetics provides protection against nausea and vomiting during multiple cycles of cisplatin-based chemotherapy. J Clin Oncol. 2003;21:4105–11.
    1. Longo F, Mansueto G, Lapadula V, et al. Palonosetron plus 3-day aprepitant and dexamethasone to prevent nausea and vomiting in patients receiving highly emetogenic chemotherapy. Sup Care Cancer. 2011;19(8):1159–64.
    1. Hesketh PJ, Kris MG, Grunberg SM, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol. 1997;15:103–9.
    1. Lindley C, McCune JS, Thomason TE, et al. Perception of chemotherapy side effects cancer versus non cancer patients. Cancer Pract. 1999;7:59–65.
    1. Basch E. The Missing Voice of Patients in Drug-Safety Reporting. N Engl J Med. 2010;362:10.

Source: PubMed

3
Suscribir