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
Summary Background Palonosetron is a second-generation 5-hydroxytryptamine 3 (5-HT3 )-receptor antagonist that has shown better efficacy than ondansetron and dolasetron in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy, and similar...
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| Veröffentlicht in: | The lancet oncology 2009-02, Vol.10 (2), p.115-124 |
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| creator | Saito, Mitsue, Dr Aogi, Kenjiro, MD Sekine, Ikuo, MD Yoshizawa, Hirohisa, MD Yanagita, Yasuhiro, MD Sakai, Hiroshi, MD Inoue, Kenichi, MD Kitagawa, Chiyoe, MD Ogura, Takashi, MD Mitsuhashi, Shoichi, MD |
| description | Summary Background Palonosetron is a second-generation 5-hydroxytryptamine 3 (5-HT3 )-receptor antagonist that has shown better efficacy than ondansetron and dolasetron in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy, and similar efficacy to ondansetron in preventing CINV in patients receiving highly emetogenic chemotherapy. In this phase III, multicentre, randomised, double-blind, double-dummy, stratified, parallel-group, active-comparator trial, we assessed the efficacy and safety of palonosetron versus granisetron for chemotherapy-induced nausea and vomiting, both of which were administered with dexamethasone in patients receiving highly emetogenic chemotherapy. Methods Between July 5, 2006, and May 31, 2007, 1143 patients with cancer who were receiving highly emetogenic chemotherapy (ie, cisplatin, or an anthracycline and cyclophosphamide combination [AC/EC]) were recruited from 75 institutions in Japan, and randomly assigned to either single-dose palonosetron (0·75 mg), or granisetron (40 μg/kg) 30 min before chemotherapy on day 1, both with dexamethasone (16 mg intravenously) on day 1 followed by additional doses (8 mg intravenously for patients receiving cisplatin or 4 mg orally for patients receiving AC/EC) on days 2 and 3. A non-deterministic minimisation method with a stochastic-biased coin was applied to the randomisation of patients. Covariates known to effect emetic risk, such as sex, age, and type of highly emetogenic chemotherapy, were used as stratification factors of minimisation to ensure balance between the treatment groups. Primary endpoints were the proportion of patients with a complete response (defined as no emetic episodes and no rescue medication) during the acute phase (0–24 h postchemotherapy; non-inferiority comparison with granisetron) and the proportion of patients with a complete response during the delayed phase (24–120 h postchemotherapy; superiority comparison with granisetron). The non-inferiority margin was predefined in the study protocol as a 10% difference between groups in the proportion of patients with complete response. The palonosetron dose of 0·75 mg was chosen on the basis of two dose-determining trials in Japanese patients. All patients who received study treatment and highly emetogenic chemotherapy were included in the efficacy analyses (modified intention to treat). This trial is registered with ClinicalTrials.gov , number NCT00359567. F |
| doi_str_mv | 10.1016/S1470-2045(08)70313-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_66877052</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1470204508703139</els_id><sourcerecordid>1659721411</sourcerecordid><originalsourceid>FETCH-LOGICAL-c445t-a86bed0fb37fc95aaa9cd2e69831f020a7c288ec2ff173563e19a3593215d9e03</originalsourceid><addsrcrecordid>eNqFkd-K1TAQxoso7rr6CErwQhS2mjRN23ihyOKfAwsK6nWYJtM9WdukJm3xvKDPZc7pUWFBvJpk8ptvZvJl2UNGnzPKqhefWVnTvKCleEqbZzXljOfyVnaa0mUuyqa5fTivyEl2L8ZrSlnNqLibnTDJuCiZOM1-foLeOx9xCt6RsZ8jMfgDBpy2EL1DsmCIKXkVwNl_U50PZAy4oJtsInxHHMwRgYAzZPGDnay7ImYO-6C3OPhpiwHG3UsCxPi57TFve-vM-e-bmYdhd05SW5PKI6YX7YcRAkx2QTKmxkg2mw2ZgoX-fnangz7ig2M8y76-e_vl4kN--fH95uLNZa7LUkw5NFWLhnYtrzstBQBIbQqsZMNZRwsKtS6aBnXRdazmouLIJHAhecGEkUj5WfZk1R2D_z5jnFSaTWPfg0M_R1VVTV1TUSTw8Q3w2s_BpdlUQakUTPA6QWKFdPAxBuzUGOwAYacYVXuX1cFltbdQ0UYdXFYy1T06is_tgOZv1dHWBLxeAUx_sVgMKmqLTqOxAfWkjLf_bfHqhoJO9lgN_TfcYfyzDFOxUHQV2WvQ5qAg-S9YZdEN</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>200951537</pqid></control><display><type>article</type><title>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</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Saito, Mitsue, Dr ; Aogi, Kenjiro, MD ; Sekine, Ikuo, MD ; Yoshizawa, Hirohisa, MD ; Yanagita, Yasuhiro, MD ; Sakai, Hiroshi, MD ; Inoue, Kenichi, MD ; Kitagawa, Chiyoe, MD ; Ogura, Takashi, MD ; Mitsuhashi, Shoichi, MD</creator><creatorcontrib>Saito, Mitsue, Dr ; Aogi, Kenjiro, MD ; Sekine, Ikuo, MD ; Yoshizawa, Hirohisa, MD ; Yanagita, Yasuhiro, MD ; Sakai, Hiroshi, MD ; Inoue, Kenichi, MD ; Kitagawa, Chiyoe, MD ; Ogura, Takashi, MD ; Mitsuhashi, Shoichi, MD</creatorcontrib><description>Summary Background Palonosetron is a second-generation 5-hydroxytryptamine 3 (5-HT3 )-receptor antagonist that has shown better efficacy than ondansetron and dolasetron in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy, and similar efficacy to ondansetron in preventing CINV in patients receiving highly emetogenic chemotherapy. In this phase III, multicentre, randomised, double-blind, double-dummy, stratified, parallel-group, active-comparator trial, we assessed the efficacy and safety of palonosetron versus granisetron for chemotherapy-induced nausea and vomiting, both of which were administered with dexamethasone in patients receiving highly emetogenic chemotherapy. Methods Between July 5, 2006, and May 31, 2007, 1143 patients with cancer who were receiving highly emetogenic chemotherapy (ie, cisplatin, or an anthracycline and cyclophosphamide combination [AC/EC]) were recruited from 75 institutions in Japan, and randomly assigned to either single-dose palonosetron (0·75 mg), or granisetron (40 μg/kg) 30 min before chemotherapy on day 1, both with dexamethasone (16 mg intravenously) on day 1 followed by additional doses (8 mg intravenously for patients receiving cisplatin or 4 mg orally for patients receiving AC/EC) on days 2 and 3. A non-deterministic minimisation method with a stochastic-biased coin was applied to the randomisation of patients. Covariates known to effect emetic risk, such as sex, age, and type of highly emetogenic chemotherapy, were used as stratification factors of minimisation to ensure balance between the treatment groups. Primary endpoints were the proportion of patients with a complete response (defined as no emetic episodes and no rescue medication) during the acute phase (0–24 h postchemotherapy; non-inferiority comparison with granisetron) and the proportion of patients with a complete response during the delayed phase (24–120 h postchemotherapy; superiority comparison with granisetron). The non-inferiority margin was predefined in the study protocol as a 10% difference between groups in the proportion of patients with complete response. The palonosetron dose of 0·75 mg was chosen on the basis of two dose-determining trials in Japanese patients. All patients who received study treatment and highly emetogenic chemotherapy were included in the efficacy analyses (modified intention to treat). This trial is registered with ClinicalTrials.gov , number NCT00359567. Findings 1114 patients were included in the efficacy analyses: 555 patients in the palonosetron group and 559 patients in the granisetron group. 418 of 555 patients (75·3%) in the palonosetron group had complete response during the acute phase compared with 410 of 559 patients (73·3%) in the granisetron group (mean difference 2·9% [95% CI −2·70 to 7·27]). During the delayed phase, 315 of 555 patients (56·8%) had complete response in the palonosetron group compared with 249 of 559 patients (44·5%) in the granisetron group (p<0·0001). The main treatment-related adverse events were constipation (97 of 557 patients [17·4%] in the palonosetron group vs 88 of 562 [15·7%] in the granisetron group) and raised concentrations of serum aminotransferases (aspartate aminotransferase: 24 of 557 [4·3%] vs 34 of 562 [6·0%]; alanine aminotransferase: 16 of 557 [2·9%] vs 33 of 562 [5·9%]); no grade 4 main treatment-related adverse events were reported. Interpretation When administered with dexamethasone before highly emetogenic chemotherapy, palonosetron exerts efficacy against chemotherapy-induced nausea and vomiting which is non-inferior to that of granisetron in the acute phase and better than that of granisetron in the delayed phase, with a comparable safety profile for the two treatments. Funding Taiho Pharmaceutical (Tokyo, Japan).</description><identifier>ISSN: 1470-2045</identifier><identifier>EISSN: 1474-5488</identifier><identifier>DOI: 10.1016/S1470-2045(08)70313-9</identifier><identifier>PMID: 19135415</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ; Antiemetics - therapeutic use ; Antineoplastic Agents - adverse effects ; Dexamethasone - therapeutic use ; Double-Blind Method ; Female ; Granisetron - therapeutic use ; Hematology, Oncology and Palliative Medicine ; Humans ; Isoquinolines - therapeutic use ; Male ; Middle Aged ; Nausea - chemically induced ; Nausea - prevention & control ; Neoplasms - drug therapy ; Quinuclidines - therapeutic use ; Serotonin Antagonists - therapeutic use ; Vomiting - chemically induced ; Vomiting - prevention & control</subject><ispartof>The lancet oncology, 2009-02, Vol.10 (2), p.115-124</ispartof><rights>Elsevier Ltd</rights><rights>2009 Elsevier Ltd</rights><rights>Copyright Elsevier Limited Feb 2009</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-a86bed0fb37fc95aaa9cd2e69831f020a7c288ec2ff173563e19a3593215d9e03</citedby><cites>FETCH-LOGICAL-c445t-a86bed0fb37fc95aaa9cd2e69831f020a7c288ec2ff173563e19a3593215d9e03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1470204508703139$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19135415$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Saito, Mitsue, Dr</creatorcontrib><creatorcontrib>Aogi, Kenjiro, MD</creatorcontrib><creatorcontrib>Sekine, Ikuo, MD</creatorcontrib><creatorcontrib>Yoshizawa, Hirohisa, MD</creatorcontrib><creatorcontrib>Yanagita, Yasuhiro, MD</creatorcontrib><creatorcontrib>Sakai, Hiroshi, MD</creatorcontrib><creatorcontrib>Inoue, Kenichi, MD</creatorcontrib><creatorcontrib>Kitagawa, Chiyoe, MD</creatorcontrib><creatorcontrib>Ogura, Takashi, MD</creatorcontrib><creatorcontrib>Mitsuhashi, Shoichi, MD</creatorcontrib><title>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</title><title>The lancet oncology</title><addtitle>Lancet Oncol</addtitle><description>Summary Background Palonosetron is a second-generation 5-hydroxytryptamine 3 (5-HT3 )-receptor antagonist that has shown better efficacy than ondansetron and dolasetron in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy, and similar efficacy to ondansetron in preventing CINV in patients receiving highly emetogenic chemotherapy. In this phase III, multicentre, randomised, double-blind, double-dummy, stratified, parallel-group, active-comparator trial, we assessed the efficacy and safety of palonosetron versus granisetron for chemotherapy-induced nausea and vomiting, both of which were administered with dexamethasone in patients receiving highly emetogenic chemotherapy. Methods Between July 5, 2006, and May 31, 2007, 1143 patients with cancer who were receiving highly emetogenic chemotherapy (ie, cisplatin, or an anthracycline and cyclophosphamide combination [AC/EC]) were recruited from 75 institutions in Japan, and randomly assigned to either single-dose palonosetron (0·75 mg), or granisetron (40 μg/kg) 30 min before chemotherapy on day 1, both with dexamethasone (16 mg intravenously) on day 1 followed by additional doses (8 mg intravenously for patients receiving cisplatin or 4 mg orally for patients receiving AC/EC) on days 2 and 3. A non-deterministic minimisation method with a stochastic-biased coin was applied to the randomisation of patients. Covariates known to effect emetic risk, such as sex, age, and type of highly emetogenic chemotherapy, were used as stratification factors of minimisation to ensure balance between the treatment groups. Primary endpoints were the proportion of patients with a complete response (defined as no emetic episodes and no rescue medication) during the acute phase (0–24 h postchemotherapy; non-inferiority comparison with granisetron) and the proportion of patients with a complete response during the delayed phase (24–120 h postchemotherapy; superiority comparison with granisetron). The non-inferiority margin was predefined in the study protocol as a 10% difference between groups in the proportion of patients with complete response. The palonosetron dose of 0·75 mg was chosen on the basis of two dose-determining trials in Japanese patients. All patients who received study treatment and highly emetogenic chemotherapy were included in the efficacy analyses (modified intention to treat). This trial is registered with ClinicalTrials.gov , number NCT00359567. Findings 1114 patients were included in the efficacy analyses: 555 patients in the palonosetron group and 559 patients in the granisetron group. 418 of 555 patients (75·3%) in the palonosetron group had complete response during the acute phase compared with 410 of 559 patients (73·3%) in the granisetron group (mean difference 2·9% [95% CI −2·70 to 7·27]). During the delayed phase, 315 of 555 patients (56·8%) had complete response in the palonosetron group compared with 249 of 559 patients (44·5%) in the granisetron group (p<0·0001). The main treatment-related adverse events were constipation (97 of 557 patients [17·4%] in the palonosetron group vs 88 of 562 [15·7%] in the granisetron group) and raised concentrations of serum aminotransferases (aspartate aminotransferase: 24 of 557 [4·3%] vs 34 of 562 [6·0%]; alanine aminotransferase: 16 of 557 [2·9%] vs 33 of 562 [5·9%]); no grade 4 main treatment-related adverse events were reported. Interpretation When administered with dexamethasone before highly emetogenic chemotherapy, palonosetron exerts efficacy against chemotherapy-induced nausea and vomiting which is non-inferior to that of granisetron in the acute phase and better than that of granisetron in the delayed phase, with a comparable safety profile for the two treatments. Funding Taiho Pharmaceutical (Tokyo, Japan).</description><subject>Adult</subject><subject>Antiemetics - therapeutic use</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Dexamethasone - therapeutic use</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Granisetron - therapeutic use</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Isoquinolines - therapeutic use</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Nausea - chemically induced</subject><subject>Nausea - prevention & control</subject><subject>Neoplasms - drug therapy</subject><subject>Quinuclidines - therapeutic use</subject><subject>Serotonin Antagonists - therapeutic use</subject><subject>Vomiting - chemically induced</subject><subject>Vomiting - prevention & control</subject><issn>1470-2045</issn><issn>1474-5488</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkd-K1TAQxoso7rr6CErwQhS2mjRN23ihyOKfAwsK6nWYJtM9WdukJm3xvKDPZc7pUWFBvJpk8ptvZvJl2UNGnzPKqhefWVnTvKCleEqbZzXljOfyVnaa0mUuyqa5fTivyEl2L8ZrSlnNqLibnTDJuCiZOM1-foLeOx9xCt6RsZ8jMfgDBpy2EL1DsmCIKXkVwNl_U50PZAy4oJtsInxHHMwRgYAzZPGDnay7ImYO-6C3OPhpiwHG3UsCxPi57TFve-vM-e-bmYdhd05SW5PKI6YX7YcRAkx2QTKmxkg2mw2ZgoX-fnangz7ig2M8y76-e_vl4kN--fH95uLNZa7LUkw5NFWLhnYtrzstBQBIbQqsZMNZRwsKtS6aBnXRdazmouLIJHAhecGEkUj5WfZk1R2D_z5jnFSaTWPfg0M_R1VVTV1TUSTw8Q3w2s_BpdlUQakUTPA6QWKFdPAxBuzUGOwAYacYVXuX1cFltbdQ0UYdXFYy1T06is_tgOZv1dHWBLxeAUx_sVgMKmqLTqOxAfWkjLf_bfHqhoJO9lgN_TfcYfyzDFOxUHQV2WvQ5qAg-S9YZdEN</recordid><startdate>20090201</startdate><enddate>20090201</enddate><creator>Saito, Mitsue, Dr</creator><creator>Aogi, Kenjiro, MD</creator><creator>Sekine, Ikuo, MD</creator><creator>Yoshizawa, Hirohisa, MD</creator><creator>Yanagita, Yasuhiro, MD</creator><creator>Sakai, Hiroshi, MD</creator><creator>Inoue, Kenichi, MD</creator><creator>Kitagawa, Chiyoe, MD</creator><creator>Ogura, Takashi, MD</creator><creator>Mitsuhashi, Shoichi, MD</creator><general>Elsevier Ltd</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>0TZ</scope><scope>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20090201</creationdate><title>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</title><author>Saito, Mitsue, Dr ; Aogi, Kenjiro, MD ; Sekine, Ikuo, MD ; Yoshizawa, Hirohisa, MD ; Yanagita, Yasuhiro, MD ; Sakai, Hiroshi, MD ; Inoue, Kenichi, MD ; Kitagawa, Chiyoe, MD ; Ogura, Takashi, MD ; Mitsuhashi, Shoichi, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-a86bed0fb37fc95aaa9cd2e69831f020a7c288ec2ff173563e19a3593215d9e03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult</topic><topic>Antiemetics - therapeutic use</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Dexamethasone - therapeutic use</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Granisetron - therapeutic use</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Isoquinolines - therapeutic use</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Nausea - chemically induced</topic><topic>Nausea - prevention & control</topic><topic>Neoplasms - drug therapy</topic><topic>Quinuclidines - therapeutic use</topic><topic>Serotonin Antagonists - therapeutic use</topic><topic>Vomiting - chemically induced</topic><topic>Vomiting - prevention & control</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Saito, Mitsue, Dr</creatorcontrib><creatorcontrib>Aogi, Kenjiro, MD</creatorcontrib><creatorcontrib>Sekine, Ikuo, MD</creatorcontrib><creatorcontrib>Yoshizawa, Hirohisa, MD</creatorcontrib><creatorcontrib>Yanagita, Yasuhiro, MD</creatorcontrib><creatorcontrib>Sakai, Hiroshi, MD</creatorcontrib><creatorcontrib>Inoue, Kenichi, MD</creatorcontrib><creatorcontrib>Kitagawa, Chiyoe, MD</creatorcontrib><creatorcontrib>Ogura, Takashi, MD</creatorcontrib><creatorcontrib>Mitsuhashi, Shoichi, MD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Pharma and Biotech Premium PRO</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Lancet Titles</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>The lancet oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Saito, Mitsue, Dr</au><au>Aogi, Kenjiro, MD</au><au>Sekine, Ikuo, MD</au><au>Yoshizawa, Hirohisa, MD</au><au>Yanagita, Yasuhiro, MD</au><au>Sakai, Hiroshi, MD</au><au>Inoue, Kenichi, MD</au><au>Kitagawa, Chiyoe, MD</au><au>Ogura, Takashi, MD</au><au>Mitsuhashi, Shoichi, MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>The lancet oncology</jtitle><addtitle>Lancet Oncol</addtitle><date>2009-02-01</date><risdate>2009</risdate><volume>10</volume><issue>2</issue><spage>115</spage><epage>124</epage><pages>115-124</pages><issn>1470-2045</issn><eissn>1474-5488</eissn><coden>LANCAO</coden><abstract>Summary Background Palonosetron is a second-generation 5-hydroxytryptamine 3 (5-HT3 )-receptor antagonist that has shown better efficacy than ondansetron and dolasetron in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy, and similar efficacy to ondansetron in preventing CINV in patients receiving highly emetogenic chemotherapy. In this phase III, multicentre, randomised, double-blind, double-dummy, stratified, parallel-group, active-comparator trial, we assessed the efficacy and safety of palonosetron versus granisetron for chemotherapy-induced nausea and vomiting, both of which were administered with dexamethasone in patients receiving highly emetogenic chemotherapy. Methods Between July 5, 2006, and May 31, 2007, 1143 patients with cancer who were receiving highly emetogenic chemotherapy (ie, cisplatin, or an anthracycline and cyclophosphamide combination [AC/EC]) were recruited from 75 institutions in Japan, and randomly assigned to either single-dose palonosetron (0·75 mg), or granisetron (40 μg/kg) 30 min before chemotherapy on day 1, both with dexamethasone (16 mg intravenously) on day 1 followed by additional doses (8 mg intravenously for patients receiving cisplatin or 4 mg orally for patients receiving AC/EC) on days 2 and 3. A non-deterministic minimisation method with a stochastic-biased coin was applied to the randomisation of patients. Covariates known to effect emetic risk, such as sex, age, and type of highly emetogenic chemotherapy, were used as stratification factors of minimisation to ensure balance between the treatment groups. Primary endpoints were the proportion of patients with a complete response (defined as no emetic episodes and no rescue medication) during the acute phase (0–24 h postchemotherapy; non-inferiority comparison with granisetron) and the proportion of patients with a complete response during the delayed phase (24–120 h postchemotherapy; superiority comparison with granisetron). The non-inferiority margin was predefined in the study protocol as a 10% difference between groups in the proportion of patients with complete response. The palonosetron dose of 0·75 mg was chosen on the basis of two dose-determining trials in Japanese patients. All patients who received study treatment and highly emetogenic chemotherapy were included in the efficacy analyses (modified intention to treat). This trial is registered with ClinicalTrials.gov , number NCT00359567. Findings 1114 patients were included in the efficacy analyses: 555 patients in the palonosetron group and 559 patients in the granisetron group. 418 of 555 patients (75·3%) in the palonosetron group had complete response during the acute phase compared with 410 of 559 patients (73·3%) in the granisetron group (mean difference 2·9% [95% CI −2·70 to 7·27]). During the delayed phase, 315 of 555 patients (56·8%) had complete response in the palonosetron group compared with 249 of 559 patients (44·5%) in the granisetron group (p<0·0001). The main treatment-related adverse events were constipation (97 of 557 patients [17·4%] in the palonosetron group vs 88 of 562 [15·7%] in the granisetron group) and raised concentrations of serum aminotransferases (aspartate aminotransferase: 24 of 557 [4·3%] vs 34 of 562 [6·0%]; alanine aminotransferase: 16 of 557 [2·9%] vs 33 of 562 [5·9%]); no grade 4 main treatment-related adverse events were reported. Interpretation When administered with dexamethasone before highly emetogenic chemotherapy, palonosetron exerts efficacy against chemotherapy-induced nausea and vomiting which is non-inferior to that of granisetron in the acute phase and better than that of granisetron in the delayed phase, with a comparable safety profile for the two treatments. Funding Taiho Pharmaceutical (Tokyo, Japan).</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>19135415</pmid><doi>10.1016/S1470-2045(08)70313-9</doi><tpages>10</tpages></addata></record> |
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| language | eng |
| recordid | cdi_proquest_miscellaneous_66877052 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adult Antiemetics - therapeutic use Antineoplastic Agents - adverse effects Dexamethasone - therapeutic use Double-Blind Method Female Granisetron - therapeutic use Hematology, Oncology and Palliative Medicine Humans Isoquinolines - therapeutic use Male Middle Aged Nausea - chemically induced Nausea - prevention & control Neoplasms - drug therapy Quinuclidines - therapeutic use Serotonin Antagonists - therapeutic use Vomiting - chemically induced Vomiting - prevention & control |
| title | 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 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T04%3A11%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Palonosetron%20plus%20dexamethasone%20versus%20granisetron%20plus%20dexamethasone%20for%20prevention%20of%20nausea%20and%20vomiting%20during%20chemotherapy:%20a%20double-blind,%20double-dummy,%20randomised,%20comparative%20phase%20III%20trial&rft.jtitle=The%20lancet%20oncology&rft.au=Saito,%20Mitsue,%20Dr&rft.date=2009-02-01&rft.volume=10&rft.issue=2&rft.spage=115&rft.epage=124&rft.pages=115-124&rft.issn=1470-2045&rft.eissn=1474-5488&rft.coden=LANCAO&rft_id=info:doi/10.1016/S1470-2045(08)70313-9&rft_dat=%3Cproquest_cross%3E1659721411%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=200951537&rft_id=info:pmid/19135415&rft_els_id=S1470204508703139&rfr_iscdi=true |