Palonosetron plus single-dose dexamethasone for the prevention of nausea and vomiting in women receiving anthracycline/cyclophosphamide-containing chemotherapy: meta-analysis of individual patient data examining the effect of age on outcome in two phase III trials
Data from two randomized trials, evaluating a single-day regimen of palonosetron plus dexamethasone against emesis due to moderately emetogenic chemotherapy, were assessed for the impact of age on outcome in a pooled sample of women receiving anthracycline and/or cyclophosphamide (AC)-containing chemotherapy.
Chemo-naïve breast cancer patients randomized to receive palonosetron (0.25 mg) plus dexamethasone (8 mg IV) on day 1 of chemotherapy (n = 200), or the same regimen followed by oral dexamethasone (8 mg) on days 2 and 3 (n = 205), were included in the analysis. The primary endpoint was complete response (CR: no vomiting and no rescue anti-emetics) in the 5-day study period. The effect of the 1-day regimen and age (<50 and ≥50 years) was investigated by a meta-analysis of individual patient data.
Younger patients comprised 43 % and 49 % of the 1-day and 3-day regimen groups, respectively; 94 % of the pooled sample received the AC combination. There were no between-treatment differences in CR rate according to age during all observation periods. In the 1-day regimen group, 55.2 % of younger patients achieved overall CR compared with 54 % of older patients. In the 3-day regimen group, 51.5 % of younger patients achieved overall CR compared with 58.7 % of older patients. In the adjusted analysis, younger age was not associated with overall CR to treatment (risk difference, −3.1 %; 95 % CI, −13.0 to 6.7 %; P = 0.533).
These results provide evidence that, irrespective of age, the dexamethasone-sparing regimen is not associated with a significant loss in overall anti-emetic protection in women undergoing AC-containing chemotherapy.
- Aapro M (2005) Optimising antiemetic therapy: what are the problems and how can they be overcome? Curr Med Res Opin 21:885–897. doi:10.1185/030079905x46313 CrossRef
- Hesketh PJ (2008) Chemotherapy-induced nausea and vomiting. N Engl J Med 358:2482–2494 CrossRef
- Roila F, Herrstedt J, Aapro M et al (2010) 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 21(suppl 5):v232–v243. doi:10.1093/annonc/mdq194 CrossRef
- Basch E, Prestrud AA, Hesketh PJ et al (2011) Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 29:4189–4198. doi:10.1200/JCO.2010.34.4614 CrossRef
- Celio L, Denaro A, Canova S, Gevorgyan A, Bajetta E (2008) Clinical update on palonosetron in the management of chemotherapy-induced nausea and vomiting. Tumori 94:447–452
- Saito M, Aogi K, Sekine I et al (2009) Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomized, comparative phase III trial. Lancet Oncol 10:115–124. doi:10.1016/s1470-2045(08)70313-9 CrossRef
- Vardy J, Chiew KS, Galica J, Pond GR, Tannock IF (2006) Side effects associated with the use of dexamethasone for prophylaxis of delayed emesis after moderately emetogenic chemotherapy. Br J Cancer 94:1011–1015. doi:10.1038/sj.bjc.6603048 CrossRef
- Olver I, Molassiotis A, Aapro M, Herrstedt J, Grunberg S, Morrow G (2011) Antiemetic research: future directions. Support Care Cancer 19(suppl 1):s49–s55. doi:10.1007/s00520-010-1036-1 CrossRef
- Aapro M, Fabi A, Nolè F, Medici M, Steger G, Bachmann C, Roncoroni S, Roila F (2010) Double-blind, randomised, controlled study of the efficacy and tolerability of palonosetron plus dexamethasone for 1 day with or without dexamethasone on days 2 and 3 in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy. Ann Oncol 21:1083–1088. doi:10.1093/annonc/mdp584 CrossRef
- Celio L, Frustaci S, Denaro A et al (2011) Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following moderately emetogenic chemotherapy: a randomized, multicenter, phase III trial. Support Care Cancer 19:1217–1225. doi:10.1007/s00520-010-0941-7 CrossRef
- Teramukai S, Matsuyama Y, Mizuno S, Sakamoto J (2004) Individual patient-level and study-level meta-analysis for investigating modifiers of treatment effect. Jpn J Clin Oncol 34:717–721. doi:10.1093/jjco/hyh138 CrossRef
- du Bois A, Vach W, Wechsel U, Holy R, Schaefer W (1996) 5-Hydroxyindoleacetic acid (5-HIAA) and cortisol excretion as predictors of chemotherapy-induced emesis. Br J Cancer 74:1137–1140 CrossRef
- Hursti TJ, Fredrikson M, Steineck G, Borjeson S, Furst CJ, Peterson C (1993) Endogenous cortisol exerts antiemetic effect similar to that of exogenous corticosteroids. Br J Cancer 68:112–114 CrossRef
- Wilkinson CW, Petrie EC, Murray SR, Colasurdo EA, Raskind MA, Peskind ER (2001) Human glucocorticoid feedback inhibition is reduced in older individuals: evening study. J Clin Endocrinol Metab 86:545–550. doi:10.1210/jc.86.2.545 CrossRef
- American Cancer Society. Breast cancer facts and figures 2009–2010. www.cancer.org/acs/groups/content/@nho/documents/document/f861009final90809pdf.pdf Accessed 26 July 2011.
- Jakobsen JN, Herrstedt J (2009) Prevention of chemotherapy-induced nausea and vomiting in elderly cancer patients. Crit Rev Oncol Hematol 71:214–221. doi:10.1016/j.critrevonc.2008.12.006 CrossRef
- Warr DG, Street JC, Carides AD (2011) Evaluation of risk factors predictive of nausea and vomiting with current standard-of-care antiemetic treatment: analysis of phase 3 trial of aprepitant in patients receiving adriamycin-cyclophosphamide-based chemotherapy. Support Care Cancer 19:807–813. doi:10.1007/s00520-010-0899-5 CrossRef
- Yap K, Leong C, Chan A (2012) Controlling chemotherapy-induced nausea and vomiting with neurokinin-1 receptor antagonists in patients on AC-based chemotherapy—are we there yet? J Cancer Ther 3:90–102. doi:10.4236/jct.2012.31012 CrossRef
- Feyer P, Jordan K (2011) Updated and new trends in antiemetic therapy: the continuing need for novel therapies. Ann Oncol 22:30–38. doi:10.1093/annonc/mdq600 CrossRef
- Booth CM, Clemons M, Dranitsaris G, Joy A, Joung S, Callaghan W, Trudeau M, Petrella T (2007) Chemotherapy-induced nausea and vomiting in breast cancer patients: a prospective observational study. J Support Oncol 5:374–380
- Palonosetron plus single-dose dexamethasone for the prevention of nausea and vomiting in women receiving anthracycline/cyclophosphamide-containing chemotherapy: meta-analysis of individual patient data examining the effect of age on outcome in two phase III trials
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Supportive Care in Cancer
Volume 21, Issue 2 , pp 565-573
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Breast cancer
- AC-containing chemotherapy
- Industry Sectors
- Author Affiliations
- 1. Medical Oncology Unit 1, Fondazione IRCCS “Istituto Nazionale Tumori”, Via Venezian 1, 20133, Milan, Italy
- 2. Section of Medical Statistics and Biometry, University of Milan, Milan, Italy
- 3. Policlinico di Monza, Istituto di Oncologia, Monza, Italy
- 4. Business Unit Oncology and Cancer Supportive Care, Helsinn Healthcare SA, Lugano, Switzerland
- 5. Scientific Department, Italfarmaco S.p.A., Cinisello Balsamo, Italy
- 6. Clinique de Genolier, Multidisciplinary Oncology Institute, Genolier, Switzerland