Efficacy, safety and pharmacokinetics of palonosetron in patients receiving highly emetogenic cisplatin-based chemotherapy:a dose-ranging clinical study

Eisenberg, Peter D.; MacKintosh, F. Roy; Ritch, Paul S.; Cornett, Patricia; Macciocchi, A.

doi:10.1093/annonc/mdh047

Cited by 139 publications

(124 citation statements)

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“…The results of a Phase II study investigating the efficacy of single doses of palonosetron 0.3-90 g/kg IV have suggested that the agent does not demonstrate a marked dose-response effect on control of emesis in patients receiving cisplatin-based chemotherapy. 73 A complete response (no emesis, no retching, no rescue therapy) was achieved in 24%, 46%, 40%, 50%, and 46% of patients who received IV palonosetron at doses of 0.3-1.0 g/kg, 3.0 g/kg, 10.0 g/kg, 30.0 g/kg, and 90.0 g/kg, respectively. No significant differences in efficacy were observed between doses of 3 g/kg and 90 g/kg, although all of these doses showed a trend toward superiority compared with the lowest dose (0.3-1.0 g/kg).…”

Section: Palonosetronmentioning

confidence: 94%

5‐hydroxytryptamine type‐3 receptor antagonists for chemotherapy‐induced and radiotherapy‐induced nausea and emesis

Aapro

Blower

2005

Cancer

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BACKGROUNDNausea and emesis as a consequence of chemotherapy or radiotherapy can have an adverse effect on patients' quality of life during cancer treatment and may last for > 5 days after administration. Guidelines suggest that, used at appropriate doses, the 5‐hydroxytryptamine type‐3 (5‐HT3) receptor antagonists—which are considered the antiemetic “gold standard” when they are administered in combination with corticosteroids—demonstrate equivalent efficacy and safety. However, due to financial considerations, these agents often are used at lower doses than recommended.METHODSA literature review of relevant publications pertaining to the control of chemotherapy‐induced nausea and emesis and dosing issues of the 5‐HT3 receptor antagonists was undertaken to provide a comprehensive review of dosing issues relevant to the 5‐HT3 receptor antagonists.RESULTSThe issue of “down dosing” was particularly pertinent because of the nature of the 5‐HT3 receptor antagonist dose‐response curve: A steep dose‐response profile within a narrow dose range suggests that antiemetic control will be lost suddenly after dose deescalation. However, the array of predisposing and confounding patient factors indicates that it is unlikely that a loss of antiemetic control will be apparent across a population; rather, individuals will experience loss of control as the dose is reduced below threshold. Of the 4 5‐HT3 receptor antagonists currently licensed in the United States (granisetron, ondansetron, dolasetron, and palonosetron), ondansetron is used sometimes at lower than optimal doses, and there is evidence to suggest that even the approved oral dose of dolasetron may be suboptimal.CONCLUSIONSSuboptimal dosing not only will be detrimental to patients' quality of life but, ultimately, will prove counterproductive in terms of hospital resources, and it will add to the already significant socioeconomic burden associated with cancer therapy. Therefore, the dose of antiemetic agent administered should be sufficiently high to ensure good emesis control across the whole patient population. Cancer 2005. © 2005 American Cancer Society.

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Section: Palonosetronmentioning

confidence: 94%

5‐hydroxytryptamine type‐3 receptor antagonists for chemotherapy‐induced and radiotherapy‐induced nausea and emesis

Aapro

Blower

2005

Cancer

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“…Two doses were identified for Phase III investigation. 11 The objective of the current Phase III trial was to evaluate the efficacy and safety of single, fixed, intravenous (i.v.) doses of palonosetron 0.25 mg and 0.75 mg compared with a single i.v.…”

mentioning

confidence: 99%

“…A Phase II study showed that palonosetron maintains efficacy in preventing CINV for some days after highly emetogenic chemotherapy. 11 The 5-HT 3 receptor binding affinity of palonosetron is approximately 100-fold greater than others in its class, making it more potent than other receptor antagonists (pKi 10.45 for palonosetron vs. 7.6 for dolasetron, 8.39 for ondansetron, and 8.91 for granisetron). 10,13 In addition, the extended plasma elimination half-life of palonosetron (approximately 40 hours) 14 is substantially longer than first-generation agents (dolasetron, 7.5 hours; ondansetron, 4.0 hours; and granisetron, 8.9 hours).…”

mentioning

confidence: 99%

Improved prevention of moderately emetogenic chemotherapy‐induced nausea and vomiting with palonosetron, a pharmacologically novel 5‐HT₃ receptor antagonist

Eisenberg

Figueroa-Vadillo

Zamora³

et al. 2003

Cancer

381

306

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BACKGROUNDPalonosetron, a highly selective and potent 5‐HT3 receptor antagonist with a strong binding affinity and a long plasma elimination half‐life (approximately 40 hours), has shown efficacy in Phase II trials in preventing chemotherapy‐induced nausea and vomiting (CINV) resulting from highly emetogenic chemotherapy. The current Phase III trial evaluated the efficacy and safety of palonosetron in preventing acute and delayed CINV after moderately emetogenic chemotherapy.METHODSIn the current study, 592 patients were randomized to receive a single, intravenous dose of palonosetron 0.25 mg, palonosetron 0.75 mg, or dolasetron 100 mg, 30 minutes before receiving moderately emetogenic chemotherapy. The primary efficacy endpoint was the proportion of patients with a complete response (CR; defined as no emetic episodes and no rescue medication) during the first 24 hours after chemotherapy. Secondary endpoints included assessment of prevention of delayed emesis (2–5 days postchemotherapy).RESULTSIn the current study, 569 patients received study medication and were included in the intent‐to‐treat efficacy analyses. CR rates during the first 24 hours were 63.0% for palonosetron 0.25 mg, 57.1% for palonosetron 0.75 mg, and 52.9% for dolasetron 100 mg. CR rates during the delayed period (24–120 hours after chemotherapy) were superior for palonosetron compared with dolasetron. Adverse events (AEs) were mostly mild to moderate and not related to study medication, with similar incidences among groups. There were no serious drug‐related AEs.CONCLUSIONSA single dose of palonosetron is as effective as a single dose of dolasetron in preventing acute CINV and superior to dolasetron in preventing delayed CINV after moderately emetogenic chemotherapy, with a comparable safety profile for all treatment groups. Cancer 2003. © 2003 American Cancer Society.

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“…A dose-ranging study of palonosetron in patients receiving chemotherapy of high emetic risk (97% received cisplatin) tested intravenous doses from 0.0003 to 0.09 mg/kg and identified 0.003 and 0.0.01 mg/kg as the lowest effective palonosetron doses [11]. Three subsequent randomized trials compared a 0.25-mg fixed palonosetron dose, a 0.75-mg fixed palonosetron dose, and a standard comparator of either intravenous ondansetron 32 mg [1,13] or intravenous dolasetron 100 mg [10].…”

Section: Dose Of 5-ht 3 Receptor Antagonistsmentioning

confidence: 99%

Consensus recommendations for the prevention of vomiting and nausea following high-emetic-risk chemotherapy

Kris

Tonato²,

Bria³

et al. 2010

Support Care Cancer

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In this update of our 2005 document, we used an evidence-based approach whenever possible to formulate recommendations, emphasizing the results of controlled trials concerning the best use of antiemetic agents for the prevention of emesis and nausea following anticancer chemotherapies of high emetic risk. A three-drug combination of a 5-hydroxytryptamine type 3 receptor (5-HT 3 ) receptor antagonist, dexamethasone, and aprepitant beginning before chemotherapy and continuing for up to 4 days remains the standard of care. We address issues of dose, schedule, and route of administration of five selective 5-HT 3 receptor antagonists. We conclude that, for each of these five drugs, there is a plateau in therapeutic efficacy above which further dose escalation does not improve outcome. In trials designed to prove the equivalence of palonosetron to ondansetron and granisetron, palonosetron proved superior in emesis prevention, while adverse effects were comparable. Furthermore, for all classes of antiemetic agents, a single dose is as effective as multiple doses or a continuous infusion. The oral route is as efficacious as the intravenous route of administration.

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Efficacy, safety and pharmacokinetics of palonosetron in patients receiving highly emetogenic cisplatin-based chemotherapy:a dose-ranging clinical study

Abstract: Palonosetron is an effective and well-tolerated agent for the prevention of CINV following highly emetogenic chemotherapy, with 3 and 10 microg/kg identified as the lowest effective palonosetron doses.

Cited by 139 publications

References 20 publications

5‐hydroxytryptamine type‐3 receptor antagonists for chemotherapy‐induced and radiotherapy‐induced nausea and emesis

5‐hydroxytryptamine type‐3 receptor antagonists for chemotherapy‐induced and radiotherapy‐induced nausea and emesis

Improved prevention of moderately emetogenic chemotherapy‐induced nausea and vomiting with palonosetron, a pharmacologically novel 5‐HT₃ receptor antagonist

Consensus recommendations for the prevention of vomiting and nausea following high-emetic-risk chemotherapy

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Efficacy, safety and pharmacokinetics of palonosetron in patients receiving highly emetogenic cisplatin-based chemotherapy:a dose-ranging clinical study

Abstract: Palonosetron is an effective and well-tolerated agent for the prevention of CINV following highly emetogenic chemotherapy, with 3 and 10 microg/kg identified as the lowest effective palonosetron doses.

Cited by 139 publications

References 20 publications

5‐hydroxytryptamine type‐3 receptor antagonists for chemotherapy‐induced and radiotherapy‐induced nausea and emesis

5‐hydroxytryptamine type‐3 receptor antagonists for chemotherapy‐induced and radiotherapy‐induced nausea and emesis

Improved prevention of moderately emetogenic chemotherapy‐induced nausea and vomiting with palonosetron, a pharmacologically novel 5‐HT3 receptor antagonist

Consensus recommendations for the prevention of vomiting and nausea following high-emetic-risk chemotherapy

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Improved prevention of moderately emetogenic chemotherapy‐induced nausea and vomiting with palonosetron, a pharmacologically novel 5‐HT₃ receptor antagonist