Prospective Multicenter Randomized Phase III Study of Weekly versus Standard Docetaxel plus Doxorubicin (D4) for First-Line Treatment of Metastatic Breast Cancer
Purpose: Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application in combination with doxor...
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| Veröffentlicht in: | Oncology 2010-01, Vol.79 (3-4), p.204-210 |
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| creator | Stemmler, Hans-Joachim Harbeck, Nadia Gröll de Rivera, Isolde Vehling Kaiser, Ursula Rauthe, Gerhard Abenhardt, Wolfgang Artmann, Almut Sommer, Harald Meerpohl, Hans-Gerd Kiechle, Marion Heinemann, Volker |
| description | Purpose: Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application in combination with doxorubicin. Methods: Patients previously untreated with chemotherapy for metastatic disease were recruited. Inclusion criteria were age 0.05). Grade 3 and grade 4 fever, diarrhea, and infections occurred more frequently in the standard arm, whereas neurotoxicity and skin/nail disorders were observed more frequently in the weekly arm. Except for fever, none of these differences reached a level of significance. Dose delays, dose reductions, and the rate of omitted doses were increased in the weekly arm. The overall response rate was 44.2% in the weekly arm compared to 52.4% in the standard arm (p = 0.52). Time to progression was 6.2 (q1w) versus 10.3 (q3w) months (p = 0.36), and overall survival was 20.5 (q1w) versus 28.7 (q3w) months (p = 0.98). Conclusion: The present data support the feasibility of both weekly and 3-weekly application of docetaxel in combination with doxorubicin. Nevertheless, given that leukopenia was similar in both arms and the efficacy parameters were at least numerically inferior with the weekly schedule, standard 3-weekly application seems to be preferable for patients requiring combination chemotherapy. |
| doi_str_mv | 10.1159/000320625 |
| format | Article |
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The present trial was initiated to compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application in combination with doxorubicin. Methods: Patients previously untreated with chemotherapy for metastatic disease were recruited. Inclusion criteria were age <65 years or a Karnofsky Performance Status of 70–100%. All patients in the D4 study received doxorubicin (50 mg/m 2 ) on the first day of treatment in addition to docetaxel given either at a 3-weekly dose of 75 mg/m 2 every 3 weeks (q3w) or at a weekly dose of 35 mg/m 2 (days 1, 8, and 15; q4w). Treatment was continued until a maximum of 8 cycles, unacceptable toxicity, or disease progression. All patients received standard corticosteroid prophylaxis. Results: Since interim analysis showed failure to reach a significant difference for the primary endpoint (hematotoxicity, i.e. leukopenia), the study was closed according to the study protocol (85 of 242 patients). A lower-than-expected rate of leukopenia ≧grade 3 was observed in the standard arm of the D4 study compared to the weekly schedule (per-patient analysis: 61.9% q3w vs. 65.1% q1w; p > 0.05). Grade 3 and grade 4 fever, diarrhea, and infections occurred more frequently in the standard arm, whereas neurotoxicity and skin/nail disorders were observed more frequently in the weekly arm. Except for fever, none of these differences reached a level of significance. Dose delays, dose reductions, and the rate of omitted doses were increased in the weekly arm. The overall response rate was 44.2% in the weekly arm compared to 52.4% in the standard arm (p = 0.52). Time to progression was 6.2 (q1w) versus 10.3 (q3w) months (p = 0.36), and overall survival was 20.5 (q1w) versus 28.7 (q3w) months (p = 0.98). Conclusion: The present data support the feasibility of both weekly and 3-weekly application of docetaxel in combination with doxorubicin. Nevertheless, given that leukopenia was similar in both arms and the efficacy parameters were at least numerically inferior with the weekly schedule, standard 3-weekly application seems to be preferable for patients requiring combination chemotherapy.</description><identifier>ISSN: 0030-2414</identifier><identifier>EISSN: 1423-0232</identifier><identifier>DOI: 10.1159/000320625</identifier><identifier>PMID: 21358208</identifier><language>eng</language><publisher>Basel, Switzerland: Karger</publisher><subject>Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - pathology ; Chemotherapy ; Clinical Study ; Doxorubicin - administration & dosage ; Female ; Gynecology. Andrology. Obstetrics ; Humans ; Liver Neoplasms - drug therapy ; Liver Neoplasms - secondary ; Lung Neoplasms - drug therapy ; Lung Neoplasms - secondary ; Lymphatic Metastasis ; Mammary gland diseases ; Medical sciences ; Metastasis ; Middle Aged ; Prospective Studies ; Skin Neoplasms - drug therapy ; Skin Neoplasms - secondary ; Survival Rate ; Taxoids - administration & dosage ; Toxicity ; Treatment Outcome ; Tumors ; Young Adult</subject><ispartof>Oncology, 2010-01, Vol.79 (3-4), p.204-210</ispartof><rights>2011 S. Karger AG, Basel</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 S. Karger AG, Basel.</rights><rights>Copyright (c) 2011 S. Karger AG, Basel</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c397t-8025e0d22fdf0e2e9926e46271e9be0e740bf4f3d7a8a4d27090c00914bec50b3</citedby><cites>FETCH-LOGICAL-c397t-8025e0d22fdf0e2e9926e46271e9be0e740bf4f3d7a8a4d27090c00914bec50b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2429,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24029798$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21358208$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stemmler, Hans-Joachim</creatorcontrib><creatorcontrib>Harbeck, Nadia</creatorcontrib><creatorcontrib>Gröll de Rivera, Isolde</creatorcontrib><creatorcontrib>Vehling Kaiser, Ursula</creatorcontrib><creatorcontrib>Rauthe, Gerhard</creatorcontrib><creatorcontrib>Abenhardt, Wolfgang</creatorcontrib><creatorcontrib>Artmann, Almut</creatorcontrib><creatorcontrib>Sommer, Harald</creatorcontrib><creatorcontrib>Meerpohl, Hans-Gerd</creatorcontrib><creatorcontrib>Kiechle, Marion</creatorcontrib><creatorcontrib>Heinemann, Volker</creatorcontrib><title>Prospective Multicenter Randomized Phase III Study of Weekly versus Standard Docetaxel plus Doxorubicin (D4) for First-Line Treatment of Metastatic Breast Cancer</title><title>Oncology</title><addtitle>Oncology</addtitle><description>Purpose: Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application in combination with doxorubicin. Methods: Patients previously untreated with chemotherapy for metastatic disease were recruited. Inclusion criteria were age <65 years or a Karnofsky Performance Status of 70–100%. All patients in the D4 study received doxorubicin (50 mg/m 2 ) on the first day of treatment in addition to docetaxel given either at a 3-weekly dose of 75 mg/m 2 every 3 weeks (q3w) or at a weekly dose of 35 mg/m 2 (days 1, 8, and 15; q4w). Treatment was continued until a maximum of 8 cycles, unacceptable toxicity, or disease progression. All patients received standard corticosteroid prophylaxis. Results: Since interim analysis showed failure to reach a significant difference for the primary endpoint (hematotoxicity, i.e. leukopenia), the study was closed according to the study protocol (85 of 242 patients). A lower-than-expected rate of leukopenia ≧grade 3 was observed in the standard arm of the D4 study compared to the weekly schedule (per-patient analysis: 61.9% q3w vs. 65.1% q1w; p > 0.05). Grade 3 and grade 4 fever, diarrhea, and infections occurred more frequently in the standard arm, whereas neurotoxicity and skin/nail disorders were observed more frequently in the weekly arm. Except for fever, none of these differences reached a level of significance. Dose delays, dose reductions, and the rate of omitted doses were increased in the weekly arm. The overall response rate was 44.2% in the weekly arm compared to 52.4% in the standard arm (p = 0.52). Time to progression was 6.2 (q1w) versus 10.3 (q3w) months (p = 0.36), and overall survival was 20.5 (q1w) versus 28.7 (q3w) months (p = 0.98). Conclusion: The present data support the feasibility of both weekly and 3-weekly application of docetaxel in combination with doxorubicin. Nevertheless, given that leukopenia was similar in both arms and the efficacy parameters were at least numerically inferior with the weekly schedule, standard 3-weekly application seems to be preferable for patients requiring combination chemotherapy.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - pathology</subject><subject>Chemotherapy</subject><subject>Clinical Study</subject><subject>Doxorubicin - administration & dosage</subject><subject>Female</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - secondary</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - secondary</subject><subject>Lymphatic Metastasis</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Prospective Studies</subject><subject>Skin Neoplasms - drug therapy</subject><subject>Skin Neoplasms - secondary</subject><subject>Survival Rate</subject><subject>Taxoids - administration & dosage</subject><subject>Toxicity</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>Young Adult</subject><issn>0030-2414</issn><issn>1423-0232</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpF0V1rFDEUBuAgil2rF96LBEGwF6MnmcxHLuuu1YUtFq14OWSSE007O1mTTOn6b_ynZtl1hUDg5ck5yQkhzxm8ZayS7wCg5FDz6gGZMcHLAnjJH5JZjqHggokT8iTGm8yaStSPyQlnZdVyaGfkz1XwcYM6uTukl9OQnMYxYaBf1Gj82v1GQ69-qoh0uVzSr2kyW-ot_Y54O2zpHYY4xRxnrIKhC68xqXsc6GbI-cLf-zD1TruRvlmIM2p9oBcuxFSs3Ij0OqBK69xvV_Iyn4xJ5QvQ9zmPic7VqDE8JY-sGiI-O-yn5NvFh-v5p2L1-eNyfr4qdCmbVLTAKwTDuTUWkKOUvEZR84ah7BGwEdBbYUvTqFYJwxuQoAEkEz3qCvrylLza190E_2vCmLobP4Uxt-zauqpEXnVGZ3uk89hiQNttglursO0YdLu_6I5_ke3LQ8GpX6M5yn_Dz-D1Aaio1WBDfq-L_50ALhu5cy_27laFHxiO4NDnL8EQmqw</recordid><startdate>20100101</startdate><enddate>20100101</enddate><creator>Stemmler, Hans-Joachim</creator><creator>Harbeck, Nadia</creator><creator>Gröll de Rivera, Isolde</creator><creator>Vehling Kaiser, Ursula</creator><creator>Rauthe, Gerhard</creator><creator>Abenhardt, Wolfgang</creator><creator>Artmann, Almut</creator><creator>Sommer, Harald</creator><creator>Meerpohl, Hans-Gerd</creator><creator>Kiechle, Marion</creator><creator>Heinemann, Volker</creator><general>Karger</general><general>S. 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Andrology. Obstetrics</topic><topic>Humans</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - secondary</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - secondary</topic><topic>Lymphatic Metastasis</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Prospective Studies</topic><topic>Skin Neoplasms - drug therapy</topic><topic>Skin Neoplasms - secondary</topic><topic>Survival Rate</topic><topic>Taxoids - administration & dosage</topic><topic>Toxicity</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stemmler, Hans-Joachim</creatorcontrib><creatorcontrib>Harbeck, Nadia</creatorcontrib><creatorcontrib>Gröll de Rivera, Isolde</creatorcontrib><creatorcontrib>Vehling Kaiser, Ursula</creatorcontrib><creatorcontrib>Rauthe, Gerhard</creatorcontrib><creatorcontrib>Abenhardt, Wolfgang</creatorcontrib><creatorcontrib>Artmann, Almut</creatorcontrib><creatorcontrib>Sommer, Harald</creatorcontrib><creatorcontrib>Meerpohl, Hans-Gerd</creatorcontrib><creatorcontrib>Kiechle, Marion</creatorcontrib><creatorcontrib>Heinemann, Volker</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</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>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</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 Basic</collection><collection>Genetics Abstracts</collection><jtitle>Oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stemmler, Hans-Joachim</au><au>Harbeck, Nadia</au><au>Gröll de Rivera, Isolde</au><au>Vehling Kaiser, Ursula</au><au>Rauthe, Gerhard</au><au>Abenhardt, Wolfgang</au><au>Artmann, Almut</au><au>Sommer, Harald</au><au>Meerpohl, Hans-Gerd</au><au>Kiechle, Marion</au><au>Heinemann, Volker</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prospective Multicenter Randomized Phase III Study of Weekly versus Standard Docetaxel plus Doxorubicin (D4) for First-Line Treatment of Metastatic Breast Cancer</atitle><jtitle>Oncology</jtitle><addtitle>Oncology</addtitle><date>2010-01-01</date><risdate>2010</risdate><volume>79</volume><issue>3-4</issue><spage>204</spage><epage>210</epage><pages>204-210</pages><issn>0030-2414</issn><eissn>1423-0232</eissn><abstract>Purpose: Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application in combination with doxorubicin. Methods: Patients previously untreated with chemotherapy for metastatic disease were recruited. Inclusion criteria were age <65 years or a Karnofsky Performance Status of 70–100%. All patients in the D4 study received doxorubicin (50 mg/m 2 ) on the first day of treatment in addition to docetaxel given either at a 3-weekly dose of 75 mg/m 2 every 3 weeks (q3w) or at a weekly dose of 35 mg/m 2 (days 1, 8, and 15; q4w). Treatment was continued until a maximum of 8 cycles, unacceptable toxicity, or disease progression. All patients received standard corticosteroid prophylaxis. Results: Since interim analysis showed failure to reach a significant difference for the primary endpoint (hematotoxicity, i.e. leukopenia), the study was closed according to the study protocol (85 of 242 patients). A lower-than-expected rate of leukopenia ≧grade 3 was observed in the standard arm of the D4 study compared to the weekly schedule (per-patient analysis: 61.9% q3w vs. 65.1% q1w; p > 0.05). Grade 3 and grade 4 fever, diarrhea, and infections occurred more frequently in the standard arm, whereas neurotoxicity and skin/nail disorders were observed more frequently in the weekly arm. Except for fever, none of these differences reached a level of significance. Dose delays, dose reductions, and the rate of omitted doses were increased in the weekly arm. The overall response rate was 44.2% in the weekly arm compared to 52.4% in the standard arm (p = 0.52). Time to progression was 6.2 (q1w) versus 10.3 (q3w) months (p = 0.36), and overall survival was 20.5 (q1w) versus 28.7 (q3w) months (p = 0.98). Conclusion: The present data support the feasibility of both weekly and 3-weekly application of docetaxel in combination with doxorubicin. Nevertheless, given that leukopenia was similar in both arms and the efficacy parameters were at least numerically inferior with the weekly schedule, standard 3-weekly application seems to be preferable for patients requiring combination chemotherapy.</abstract><cop>Basel, Switzerland</cop><pub>Karger</pub><pmid>21358208</pmid><doi>10.1159/000320625</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aged Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - pathology Chemotherapy Clinical Study Doxorubicin - administration & dosage Female Gynecology. Andrology. Obstetrics Humans Liver Neoplasms - drug therapy Liver Neoplasms - secondary Lung Neoplasms - drug therapy Lung Neoplasms - secondary Lymphatic Metastasis Mammary gland diseases Medical sciences Metastasis Middle Aged Prospective Studies Skin Neoplasms - drug therapy Skin Neoplasms - secondary Survival Rate Taxoids - administration & dosage Toxicity Treatment Outcome Tumors Young Adult |
| title | Prospective Multicenter Randomized Phase III Study of Weekly versus Standard Docetaxel plus Doxorubicin (D4) for First-Line Treatment of Metastatic Breast Cancer |
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