Bevacizumab in combination with sequential high-dose chemotherapy in solid cancer, a feasibility study
We evaluated the feasibility and toxicity of bevacizumab in combination with sequential high-dose (HD) ifosfamide, carboplatin and etoposide refractory to standard chemotherapy in patients with sarcoma and germ cell cancer (GCC). Sixteen patients (13 sarcomas, 3 GCC) received SD-ICE followed by 4 cy...
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| Veröffentlicht in: | Bone marrow transplantation (Basingstoke) 2010-12, Vol.45 (12), p.1704-1709 |
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| creator | Jordan, K Wolf, H H Voigt, W Kegel, T Mueller, L P Behlendorf, T Sippel, C Arnold, D Schmoll, H J |
| description | We evaluated the feasibility and toxicity of bevacizumab in combination with sequential high-dose (HD) ifosfamide, carboplatin and etoposide refractory to standard chemotherapy in patients with sarcoma and germ cell cancer (GCC). Sixteen patients (13 sarcomas, 3 GCC) received SD-ICE followed by 4 cycles of HD-ICE, qd22 with stem cell support in combination with bevacizumab. All 16 patients were evaluable for toxicity and efficacy, and received 51 cycles (median 3.3). There was no increase in toxicity except of a relatively high incidence of ifosfamide encephalopathy in 17 cycles when compared with previous HD-ICE protocols. One almost complete response in the patient with GCC, previously progressive with three preceding protocols, was observed. Six patients had a partial response (sarcoma 4/13 patients; GCC 2/3 patients), and five patients stable disease (sarcoma 5/13 patients). The median PFS/OS for sarcoma was 5 months (confidence interval (CI): 3.1–6.9) and 13 months (CI: 3.6–24.4), respectively. To our knowledge, this is the first report of the addition of bevacizumab to HD-ICE. This combination did not show new unexpected toxicities except for a relatively high rate of ifosfamide encephalopathy. The efficacy in these heavily pretreated patients including possible reversal of chemotherapy resistance by the addition of bevacizumab indicates a possible potential of bevacizumab in this combination. |
| doi_str_mv | 10.1038/bmt.2010.50 |
| format | Article |
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Sixteen patients (13 sarcomas, 3 GCC) received SD-ICE followed by 4 cycles of HD-ICE, qd22 with stem cell support in combination with bevacizumab. All 16 patients were evaluable for toxicity and efficacy, and received 51 cycles (median 3.3). There was no increase in toxicity except of a relatively high incidence of ifosfamide encephalopathy in 17 cycles when compared with previous HD-ICE protocols. One almost complete response in the patient with GCC, previously progressive with three preceding protocols, was observed. Six patients had a partial response (sarcoma 4/13 patients; GCC 2/3 patients), and five patients stable disease (sarcoma 5/13 patients). The median PFS/OS for sarcoma was 5 months (confidence interval (CI): 3.1–6.9) and 13 months (CI: 3.6–24.4), respectively. To our knowledge, this is the first report of the addition of bevacizumab to HD-ICE. This combination did not show new unexpected toxicities except for a relatively high rate of ifosfamide encephalopathy. The efficacy in these heavily pretreated patients including possible reversal of chemotherapy resistance by the addition of bevacizumab indicates a possible potential of bevacizumab in this combination.</description><identifier>ISSN: 0268-3369</identifier><identifier>EISSN: 1476-5365</identifier><identifier>DOI: 10.1038/bmt.2010.50</identifier><identifier>PMID: 20228848</identifier><identifier>CODEN: BMTRE9</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/92/436/108 ; 692/699/67/1679 ; 692/699/67/1798 ; 692/700/565/1436/1437 ; Adult ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - adverse effects ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Bevacizumab ; Biological and medical sciences ; Bone marrow ; Bone marrow, stem cells transplantation. Graft versus host reaction ; Cancer ; Carboplatin ; Carboplatin - administration & dosage ; Carboplatin - adverse effects ; Care and treatment ; Cell Biology ; Chemoresistance ; Chemotherapy ; Combined Modality Therapy ; Confidence intervals ; Dosage and administration ; Encephalopathy ; Etoposide ; Etoposide - administration & dosage ; Etoposide - adverse effects ; Feasibility Studies ; Female ; Hematology ; Humans ; Ifosfamide ; Ifosfamide - administration & dosage ; Ifosfamide - adverse effects ; Internal Medicine ; Male ; Medical sciences ; Medicine ; Medicine & Public Health ; Middle Aged ; Monoclonal antibodies ; Neoplasms, Germ Cell and Embryonal - drug therapy ; Neoplasms, Germ Cell and Embryonal - surgery ; original-article ; Peripheral Blood Stem Cell Transplantation ; Public Health ; Sarcoma ; Sarcoma - drug therapy ; Sarcoma - surgery ; Stem cell transplantation ; Stem Cells ; Targeted cancer therapy ; Toxicity ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Young Adult</subject><ispartof>Bone marrow transplantation (Basingstoke), 2010-12, Vol.45 (12), p.1704-1709</ispartof><rights>Macmillan Publishers Limited 2010</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2010 Nature Publishing Group</rights><rights>Macmillan Publishers Limited 2010.</rights><rights>Copyright Nature Publishing Group Dec 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c545t-f7f346a79c7a099e4716daef31cd6d33d0ebb7ede87962d3c9fc52e2194040a93</citedby><cites>FETCH-LOGICAL-c545t-f7f346a79c7a099e4716daef31cd6d33d0ebb7ede87962d3c9fc52e2194040a93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/bmt.2010.50$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/bmt.2010.50$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23651176$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20228848$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jordan, K</creatorcontrib><creatorcontrib>Wolf, H H</creatorcontrib><creatorcontrib>Voigt, W</creatorcontrib><creatorcontrib>Kegel, T</creatorcontrib><creatorcontrib>Mueller, L P</creatorcontrib><creatorcontrib>Behlendorf, T</creatorcontrib><creatorcontrib>Sippel, C</creatorcontrib><creatorcontrib>Arnold, D</creatorcontrib><creatorcontrib>Schmoll, H J</creatorcontrib><title>Bevacizumab in combination with sequential high-dose chemotherapy in solid cancer, a feasibility study</title><title>Bone marrow transplantation (Basingstoke)</title><addtitle>Bone Marrow Transplant</addtitle><addtitle>Bone Marrow Transplant</addtitle><description>We evaluated the feasibility and toxicity of bevacizumab in combination with sequential high-dose (HD) ifosfamide, carboplatin and etoposide refractory to standard chemotherapy in patients with sarcoma and germ cell cancer (GCC). Sixteen patients (13 sarcomas, 3 GCC) received SD-ICE followed by 4 cycles of HD-ICE, qd22 with stem cell support in combination with bevacizumab. All 16 patients were evaluable for toxicity and efficacy, and received 51 cycles (median 3.3). There was no increase in toxicity except of a relatively high incidence of ifosfamide encephalopathy in 17 cycles when compared with previous HD-ICE protocols. One almost complete response in the patient with GCC, previously progressive with three preceding protocols, was observed. Six patients had a partial response (sarcoma 4/13 patients; GCC 2/3 patients), and five patients stable disease (sarcoma 5/13 patients). The median PFS/OS for sarcoma was 5 months (confidence interval (CI): 3.1–6.9) and 13 months (CI: 3.6–24.4), respectively. To our knowledge, this is the first report of the addition of bevacizumab to HD-ICE. This combination did not show new unexpected toxicities except for a relatively high rate of ifosfamide encephalopathy. The efficacy in these heavily pretreated patients including possible reversal of chemotherapy resistance by the addition of bevacizumab indicates a possible potential of bevacizumab in this combination.</description><subject>631/92/436/108</subject><subject>692/699/67/1679</subject><subject>692/699/67/1798</subject><subject>692/700/565/1436/1437</subject><subject>Adult</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal - adverse effects</subject><subject>Antibodies, Monoclonal, Humanized</subject><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Bevacizumab</subject><subject>Biological and medical sciences</subject><subject>Bone marrow</subject><subject>Bone marrow, stem cells transplantation. Graft versus host reaction</subject><subject>Cancer</subject><subject>Carboplatin</subject><subject>Carboplatin - administration & dosage</subject><subject>Carboplatin - adverse effects</subject><subject>Care and treatment</subject><subject>Cell Biology</subject><subject>Chemoresistance</subject><subject>Chemotherapy</subject><subject>Combined Modality Therapy</subject><subject>Confidence intervals</subject><subject>Dosage and administration</subject><subject>Encephalopathy</subject><subject>Etoposide</subject><subject>Etoposide - administration & dosage</subject><subject>Etoposide - adverse effects</subject><subject>Feasibility Studies</subject><subject>Female</subject><subject>Hematology</subject><subject>Humans</subject><subject>Ifosfamide</subject><subject>Ifosfamide - administration & dosage</subject><subject>Ifosfamide - adverse effects</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Neoplasms, Germ Cell and Embryonal - drug therapy</subject><subject>Neoplasms, Germ Cell and Embryonal - surgery</subject><subject>original-article</subject><subject>Peripheral Blood Stem Cell Transplantation</subject><subject>Public Health</subject><subject>Sarcoma</subject><subject>Sarcoma - drug therapy</subject><subject>Sarcoma - surgery</subject><subject>Stem cell transplantation</subject><subject>Stem Cells</subject><subject>Targeted cancer therapy</subject><subject>Toxicity</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><subject>Young Adult</subject><issn>0268-3369</issn><issn>1476-5365</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp10k1v1DAQBmALgehSOHFHFgguNIu_4iTHtuJLqsQFzpZjjzeuknixHdDy6-vVLrSVinKIEj_jiecNQi8pWVPC2w_9lNeMlKeaPEIrKhpZ1VzWj9GKMNlWnMvuBD1L6ZoQKgSpn6ITRhhrW9GukLuAX9r4P8uke-xnbMLU-1lnH2b82-cBJ_i5wJy9HvHgN0NlQwJsBphCHiDq7W5flcLoLTZ6NhDPsMYOdPK9H33e4ZQXu3uOnjg9JnhxvJ-iH58-fr_8Ul19-_z18vyqMrWoc-Uax4XUTWcaTboOREOl1eA4NVZazi2Bvm_AQtt0klluOmdqBox2ggiiO36KXh_23cZQvjtldR2WOJeWqqVSNowKVtCb_yEmRSFSsjtqo0dQfnYhR20mn4w6Z6LmHed033D9gCqXhcmbMIPz5f29gnd3CgbQYx7K-Jb9xNN9-P4ATQwpRXBqG_2k405RovbBqxK82gevalL0q-OZln4C-8_-TbqAt0egk9GjiyUsn25d-WMobWRxZweXytK8gXg7nIf63gAMW8JK</recordid><startdate>20101201</startdate><enddate>20101201</enddate><creator>Jordan, K</creator><creator>Wolf, H H</creator><creator>Voigt, W</creator><creator>Kegel, T</creator><creator>Mueller, L P</creator><creator>Behlendorf, T</creator><creator>Sippel, C</creator><creator>Arnold, D</creator><creator>Schmoll, H J</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>IQODW</scope><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>3V.</scope><scope>7QO</scope><scope>7QP</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20101201</creationdate><title>Bevacizumab in combination with sequential high-dose chemotherapy in solid cancer, a feasibility study</title><author>Jordan, K ; Wolf, H H ; Voigt, W ; Kegel, T ; Mueller, L P ; Behlendorf, T ; Sippel, C ; Arnold, D ; Schmoll, H J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c545t-f7f346a79c7a099e4716daef31cd6d33d0ebb7ede87962d3c9fc52e2194040a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>631/92/436/108</topic><topic>692/699/67/1679</topic><topic>692/699/67/1798</topic><topic>692/700/565/1436/1437</topic><topic>Adult</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal - adverse effects</topic><topic>Antibodies, Monoclonal, Humanized</topic><topic>Antineoplastic Combined Chemotherapy Protocols - adverse effects</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Bevacizumab</topic><topic>Biological and medical sciences</topic><topic>Bone marrow</topic><topic>Bone marrow, stem cells transplantation. Graft versus host reaction</topic><topic>Cancer</topic><topic>Carboplatin</topic><topic>Carboplatin - administration & dosage</topic><topic>Carboplatin - adverse effects</topic><topic>Care and treatment</topic><topic>Cell Biology</topic><topic>Chemoresistance</topic><topic>Chemotherapy</topic><topic>Combined Modality Therapy</topic><topic>Confidence intervals</topic><topic>Dosage and administration</topic><topic>Encephalopathy</topic><topic>Etoposide</topic><topic>Etoposide - administration & dosage</topic><topic>Etoposide - adverse effects</topic><topic>Feasibility Studies</topic><topic>Female</topic><topic>Hematology</topic><topic>Humans</topic><topic>Ifosfamide</topic><topic>Ifosfamide - administration & dosage</topic><topic>Ifosfamide - adverse effects</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>Neoplasms, Germ Cell and Embryonal - drug therapy</topic><topic>Neoplasms, Germ Cell and Embryonal - surgery</topic><topic>original-article</topic><topic>Peripheral Blood Stem Cell Transplantation</topic><topic>Public Health</topic><topic>Sarcoma</topic><topic>Sarcoma - drug therapy</topic><topic>Sarcoma - surgery</topic><topic>Stem cell transplantation</topic><topic>Stem Cells</topic><topic>Targeted cancer therapy</topic><topic>Toxicity</topic><topic>Transfusions. 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Sixteen patients (13 sarcomas, 3 GCC) received SD-ICE followed by 4 cycles of HD-ICE, qd22 with stem cell support in combination with bevacizumab. All 16 patients were evaluable for toxicity and efficacy, and received 51 cycles (median 3.3). There was no increase in toxicity except of a relatively high incidence of ifosfamide encephalopathy in 17 cycles when compared with previous HD-ICE protocols. One almost complete response in the patient with GCC, previously progressive with three preceding protocols, was observed. Six patients had a partial response (sarcoma 4/13 patients; GCC 2/3 patients), and five patients stable disease (sarcoma 5/13 patients). The median PFS/OS for sarcoma was 5 months (confidence interval (CI): 3.1–6.9) and 13 months (CI: 3.6–24.4), respectively. To our knowledge, this is the first report of the addition of bevacizumab to HD-ICE. This combination did not show new unexpected toxicities except for a relatively high rate of ifosfamide encephalopathy. The efficacy in these heavily pretreated patients including possible reversal of chemotherapy resistance by the addition of bevacizumab indicates a possible potential of bevacizumab in this combination.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>20228848</pmid><doi>10.1038/bmt.2010.50</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 0268-3369 1476-5365 |
| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature; EZB-FREE-00999 freely available EZB journals |
| subjects | 631/92/436/108 692/699/67/1679 692/699/67/1798 692/700/565/1436/1437 Adult Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - adverse effects Antibodies, Monoclonal, Humanized Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - therapeutic use Bevacizumab Biological and medical sciences Bone marrow Bone marrow, stem cells transplantation. Graft versus host reaction Cancer Carboplatin Carboplatin - administration & dosage Carboplatin - adverse effects Care and treatment Cell Biology Chemoresistance Chemotherapy Combined Modality Therapy Confidence intervals Dosage and administration Encephalopathy Etoposide Etoposide - administration & dosage Etoposide - adverse effects Feasibility Studies Female Hematology Humans Ifosfamide Ifosfamide - administration & dosage Ifosfamide - adverse effects Internal Medicine Male Medical sciences Medicine Medicine & Public Health Middle Aged Monoclonal antibodies Neoplasms, Germ Cell and Embryonal - drug therapy Neoplasms, Germ Cell and Embryonal - surgery original-article Peripheral Blood Stem Cell Transplantation Public Health Sarcoma Sarcoma - drug therapy Sarcoma - surgery Stem cell transplantation Stem Cells Targeted cancer therapy Toxicity Transfusions. Complications. Transfusion reactions. Cell and gene therapy Young Adult |
| title | Bevacizumab in combination with sequential high-dose chemotherapy in solid cancer, a feasibility study |
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