Multicenter, randomised, controlled study to compare palonosetron plus dexamethasone before chemotherapy administration versus the same regimen with dexamethasone continuing on days 2 and 3 in preventing nausea and vomiting in patients with solid tumors treated with moderately emetogenic chemotherapy

Nel maggio 2006 é stato avviato uno studio multicentrico per la profilassi dell’emesi in pazienti con neoplasie solide candidati a trattamento con regimi chemioterapici moderatamente emetizzanti.

Lo studio (Protocollo 07/06) aveva l’obiettivo di valutare l’ efficacia e sicurezza di palenosetron in associazione a desametasone.

Sono stati  arruolati 334 pazienti.

Lo studio ha dimostrato che è possibile ridurre la dose di desametasone in associazione al palonosetron  per la prevenzione dell’emesi acuta e ritardata da chemioterapia moderatamente emetogena.

Centri  partecipanti :                            Fondazione IRCCS Istituto Nazionale Tumori, MILANO

Centro di Riferimento Oncologico, AVIANO (PN)

Ospedale G. da Saliceto, PIACENZA

Ospedale S.Gerardo, MONZA (MI)

Istituti Ospitalieri di CREMONA

Ospedale Maggiore della Carità di NOVARA

Presidio Ospedaliero di GORGONZOLA (MI)

Ospedale di Circolo e Fondazione Macchi, VARESE

Ospedale Oncologico Regionale di RIONERO IN VULTURE (PZ)

Ospedale Civile di Sondrio, SONDRIO

Az. Ospedaliera Carlo Poma, MANTOVA

Ospedale S. Luigi Gonzaga, ORBASSANO

Policlinico P. Giaccone, PALERMO

Ospedale L. Sacco, MILANO

IFO/IRE Istituto Regina Elena, ROMA

Riferimenti Bibliografici:

  • Clinical update on palonosetron in the management of chemotherapy-induced nausea and vomiting.
    (L. Celio, A. Denaro, S. Canova, A. Gevorgyan, E. Bajetta)
    Tumori. 2008 Jul-Aug;94(4):447-52.


    The need to control chemotherapy-induced nausea and vomiting is continuously stimulating research to find better options for the optimal antiemetic care. Palonosetron is different from conventional serotonin receptor antagonists not only by the fact of having a longer half-life but also by higher binding affinity for serotonin receptors. It is the first agent in the class which is approved for preventing both delayed and acute emesis induced by moderately emetogenic chemotherapy. Recent studies using palonosetron-based antiemetic regimens, as well as in the clinical setting of multiple-day chemotherapy, have been reported. Palonosetron plus dexamethasone given as a pre-treatment infusion was effective for preventing acute and delayed emesis after moderately emetogenic chemotherapy. Palonosetron in combination with dexamethasone and aprepitant was highly effective in preventing emesis in the days following administration of moderately emetogenic chemotherapy. Treatment was well tolerated, with no unexpected adverse events. Multiple-day dosing of palonosetron plus dexamethasone was safe and effective for prevention of emesis induced by 5-day cisplatin-based chemotherapy. There was no evidence of cumulative toxicity when palonosetron was given three times over 5 days. Further evidence from ongoing clinical trials with palonosetron with or without dexamethasone will be available soon. Palonosetron represents an useful addition to the therapeutic armamentarium for the management of chemotherapy-induced nausea and vomiting. Further studies are needed to assess the effectiveness of palonosetron in combination with dexamethasone compared with that of older serotonin receptor antagonists combined with dexamethasone. However, palonosetron may offer advantages of convenience over the short-acting older antagonists due to its ability to be given as a single intravenous dose prior to chemotherapy.

    PMID: 18822676   [PubMed – indexed for MEDLINE]

    Download articolo: Tumori, 94: 447-452, 2008


  • 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.
    (Celio L, Frustaci S, Denaro A, Buonadonna A, Ardizzoia A, Piazza E, Fabi A, Capobianco AM, Isa L, Cavanna L, Bertolini A, Bichisao E, Bajetta E; Italian Trials in Medical Oncology Group).
    Support Care Cancer. 2011 Aug;19(8):1217-25. doi: 10.1007/s00520-010-0941-7. Epub 2010 Jun 25.


    A phase III trial assessed the efficacy of palonosetron plus dexamethasone given once in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) following a broad range of moderately emetogenic chemotherapy (MEC) regimens.

    This multicentre, randomized, open-label, non-inferiority trial evaluated two different treatment groups. One group received palonosetron (0.25 mg intravenously) and dexamethasone (8 mg intravenously) before chemotherapy, while the other was administered the same regimen on day 1 followed by dexamethasone 8 mg orally on days 2 and 3. The primary endpoint was complete response (CR; defined as no emetic episodes and no rescue medication) during the overall phase (days 1-5 after chemotherapy initiation). The non-inferiority margin was predefined as a 15% difference between groups in the primary endpoint.

    Of 332 chemotherapy-naïve patients included in the intention-to-treat analysis, 65.1% were female, and 35.2% received anthracycline plus cyclophosphamide (AC)-based regimens. Overall CR rates were 67.5% for those administered dexamethasone only on day 1 (n = 166), and 71.1% for those also administered dexamethasone on days 2 and 3 (n = 166; difference -3.6% (95% confidence interval, -13.5 to 6.3)). CR rates were not significantly different between groups during the acute (0-24 h post-chemotherapy; 88.6% versus 84.3%; P = 0.262) and delayed phases (days 2-5; 68.7% versus 77.7%; P = 0.116).

    Palonosetron plus single-dose dexamethasone administered before common MEC regimens provide protection against acute and delayed CINV which is non-inferior to that of palonosetron plus dexamethasone for 3 days. However, the major benefit of the single-day regimen occurs in patients receiving non-AC MEC regimens.

    PMID: 20574663   [PubMed – indexed for MEDLINE]   PMCID: PMC3128271

    Download articolo: Supportive Care Center 2010

  • Palonosetron plus 1-day dexamethasone for the prevention of nausea and vomiting due to moderately emetogenic chemotherapy: effect of established risk factors on treatment outcome in a phase III trial.
    (Celio L, Denaro A, Agustoni F, Bajetta E).
    J Support Oncol. 2012 Mar-Apr;10(2):65-71. doi: 10.1016/j.suponc.2011.06.007. Epub 2011 Sep 23.


    The non-inferiority of palonosetron plus 1-day versus 3-day dexamethasone in preventing chemotherapy-induced nausea and vomiting (CINV) due to moderately emetogenic chemotherapy (MEC) has been previously demonstrated.

    The objectives of this prespecified post hoc analysis were to demonstrate the non-inferiority hypothesis in an adjusted model for known risk factors (age, gender, alcohol consumption, and type of MEC [anthracycline plus cyclophosphamide (AC)-based versus other MEC]) for CINV and to explore the impact on antiemetic outcome of these risk factors.

    Chemonaive patients (n = 324) with solid tumors were randomized to receive palonosetron 0.25 mg IV plus dexamethasone 8 mg IV on day 1 of chemotherapy or the same regimen followed by oral dexamethasone 8 mg on days 2 and 3. The primary end point was complete response (CR, no emesis and no rescue antiemetics) during the 5-day study period. A modified intention-to-treat approach was used for multivariable analysis.

    Non-inferiority of the 1-day regimen was confirmed even after adjusting for risk factors (risk difference -4.4%, 95% CI -14.1% to 5.4%; P = .381). Only age less than 50 years (P = .044) independently predicted a poor outcome of antiemetic treatment. However, most of the younger patients were women (1-day regimen 81.8%, 3-day regimen 88.4%) who underwent AC-based chemotherapy (1-day regimen 61.1%, 3-day regimen 71.0%). There were no significant between-treatment differences in the CR rate according to risk factors.

    This analysis confirmed that the 1-day regimen provides a valid treatment option for prevention of CINV in delayed, non-AC-based MEC.

    PMID: 22005217   [PubMed – indexed for MEDLINE]

    Download articolo: J Support Oncol. 2012 Mar-Apr;10(2):65-71