Hyperthermic Isolated Perfusion with Tumor Necrosis Factor-alpha and Doxorubicin for the Treatment of Limb-Threatening Soft Tissue Sarcoma: The Experience of the Italian Society of Integrated Locoregional Treatment in Oncology (SITILO)

Background: Tumor necrosis factor-alpha (TNFα)-based hyperthermic isolated limb perfusion (HILP) is routinely carried out at most oncological institutions in the treatment of locally advanced soft tissue limb sarcoma (STS), employing high TNFα dosages. After a phase I-II study, the SITILO (Italian...

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Veröffentlicht in:In vivo (Athens) 2009-03, Vol.23 (2), p.363
Hauptverfasser: Di Filippo, F, Giacomini, P, Rossi, C R, Santinami, M, Garinei, R, Anzà, M, Deraco, M, Botti, C, Perri, P, Cavaliere, F, Di Angelo, P, Sofra, C, Sperduti, I, Pasqualoni, R, Di Filippo, S, Corrias, F, Armenti, A, Ferraresi, V
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container_issue 2
container_start_page 363
container_title In vivo (Athens)
container_volume 23
creator Di Filippo, F
Giacomini, P
Rossi, C R
Santinami, M
Garinei, R
Anzà, M
Deraco, M
Botti, C
Perri, P
Cavaliere, F
Di Angelo, P
Sofra, C
Sperduti, I
Pasqualoni, R
Di Filippo, S
Corrias, F
Armenti, A
Ferraresi, V
description Background: Tumor necrosis factor-alpha (TNFα)-based hyperthermic isolated limb perfusion (HILP) is routinely carried out at most oncological institutions in the treatment of locally advanced soft tissue limb sarcoma (STS), employing high TNFα dosages. After a phase I-II study, the SITILO (Italian Society of Integrated Locoregional Therapies in Oncology) centers began to employ the lower dose of 1 mg of TNFα. The aim of this paper is to report on the results obtained in 75 patients with limb-threatening STS treated with a low TNFα dose and doxorubicin (Dx). Patients and Methods: HILP with TNFα (at a dosage of either ≤1 mg or >1 mg) and Dx was administered to 75 patients with limb-threatening STS: 37 males and 38 females; median age 50 years; tumor in the lower and upper limbs in 58 and 17 patients, respectively; primary and recurrent tumors in 45 and 30 patients, respectively. Most tumors (77%) were high grade. Tumor resection was carried out 6 to 8 weeks after HILP. Results: The grade of limb toxicity was mild to moderate in the vast majority of patients (76%). Grades IV and V were observed, but only when high muscle temperatures were recorded and high TNFα dosages were employed. Systemic toxicity was also mild to moderate and there were no postoperative deaths. Complete and partial tumor responses were 34% and 48%, respectively, with an overall response of 82% . Limb sparing surgery was carried out in 85.3% of patients. At a median follow-up of 28 months, 16 recurrences (21.3%) were recorded, with a 5-year locoregional disease-free survival of 63% . The 5-year disease-free survival and overall survival were 36.7% and 61.6%, respectively. Conclusion: HILP with 1 mg of TNFα is an effective neoadjuvant therapy resulting in a high rate of limb sparing in limb-threatening STS, with acceptable local reactions and negligible systemic toxicity.
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After a phase I-II study, the SITILO (Italian Society of Integrated Locoregional Therapies in Oncology) centers began to employ the lower dose of 1 mg of TNFα. The aim of this paper is to report on the results obtained in 75 patients with limb-threatening STS treated with a low TNFα dose and doxorubicin (Dx). Patients and Methods: HILP with TNFα (at a dosage of either ≤1 mg or &gt;1 mg) and Dx was administered to 75 patients with limb-threatening STS: 37 males and 38 females; median age 50 years; tumor in the lower and upper limbs in 58 and 17 patients, respectively; primary and recurrent tumors in 45 and 30 patients, respectively. Most tumors (77%) were high grade. Tumor resection was carried out 6 to 8 weeks after HILP. Results: The grade of limb toxicity was mild to moderate in the vast majority of patients (76%). Grades IV and V were observed, but only when high muscle temperatures were recorded and high TNFα dosages were employed. Systemic toxicity was also mild to moderate and there were no postoperative deaths. Complete and partial tumor responses were 34% and 48%, respectively, with an overall response of 82% . Limb sparing surgery was carried out in 85.3% of patients. At a median follow-up of 28 months, 16 recurrences (21.3%) were recorded, with a 5-year locoregional disease-free survival of 63% . The 5-year disease-free survival and overall survival were 36.7% and 61.6%, respectively. Conclusion: HILP with 1 mg of TNFα is an effective neoadjuvant therapy resulting in a high rate of limb sparing in limb-threatening STS, with acceptable local reactions and negligible systemic toxicity.</description><identifier>ISSN: 0258-851X</identifier><identifier>EISSN: 1791-7549</identifier><identifier>PMID: 19414428</identifier><language>eng</language><publisher>Greece: International Institute of Anticancer Research</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols - administration &amp; dosage ; Chemotherapy, Cancer, Regional Perfusion - methods ; Disease-Free Survival ; Doxorubicin - administration &amp; dosage ; Extremities - pathology ; Female ; Humans ; Hyperthermia, Induced ; Male ; Middle Aged ; Perfusion ; Recurrence ; Sarcoma - drug therapy ; Soft Tissue Neoplasms - drug therapy ; Treatment Outcome ; Tumor Necrosis Factor-alpha - administration &amp; dosage</subject><ispartof>In vivo (Athens), 2009-03, Vol.23 (2), p.363</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19414428$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Di Filippo, F</creatorcontrib><creatorcontrib>Giacomini, P</creatorcontrib><creatorcontrib>Rossi, C R</creatorcontrib><creatorcontrib>Santinami, M</creatorcontrib><creatorcontrib>Garinei, R</creatorcontrib><creatorcontrib>Anzà, M</creatorcontrib><creatorcontrib>Deraco, M</creatorcontrib><creatorcontrib>Botti, C</creatorcontrib><creatorcontrib>Perri, P</creatorcontrib><creatorcontrib>Cavaliere, F</creatorcontrib><creatorcontrib>Di Angelo, P</creatorcontrib><creatorcontrib>Sofra, C</creatorcontrib><creatorcontrib>Sperduti, I</creatorcontrib><creatorcontrib>Pasqualoni, R</creatorcontrib><creatorcontrib>Di Filippo, S</creatorcontrib><creatorcontrib>Corrias, F</creatorcontrib><creatorcontrib>Armenti, A</creatorcontrib><creatorcontrib>Ferraresi, V</creatorcontrib><title>Hyperthermic Isolated Perfusion with Tumor Necrosis Factor-alpha and Doxorubicin for the Treatment of Limb-Threatening Soft Tissue Sarcoma: The Experience of the Italian Society of Integrated Locoregional Treatment in Oncology (SITILO)</title><title>In vivo (Athens)</title><addtitle>In Vivo</addtitle><description>Background: Tumor necrosis factor-alpha (TNFα)-based hyperthermic isolated limb perfusion (HILP) is routinely carried out at most oncological institutions in the treatment of locally advanced soft tissue limb sarcoma (STS), employing high TNFα dosages. After a phase I-II study, the SITILO (Italian Society of Integrated Locoregional Therapies in Oncology) centers began to employ the lower dose of 1 mg of TNFα. The aim of this paper is to report on the results obtained in 75 patients with limb-threatening STS treated with a low TNFα dose and doxorubicin (Dx). Patients and Methods: HILP with TNFα (at a dosage of either ≤1 mg or &gt;1 mg) and Dx was administered to 75 patients with limb-threatening STS: 37 males and 38 females; median age 50 years; tumor in the lower and upper limbs in 58 and 17 patients, respectively; primary and recurrent tumors in 45 and 30 patients, respectively. Most tumors (77%) were high grade. Tumor resection was carried out 6 to 8 weeks after HILP. Results: The grade of limb toxicity was mild to moderate in the vast majority of patients (76%). Grades IV and V were observed, but only when high muscle temperatures were recorded and high TNFα dosages were employed. Systemic toxicity was also mild to moderate and there were no postoperative deaths. Complete and partial tumor responses were 34% and 48%, respectively, with an overall response of 82% . Limb sparing surgery was carried out in 85.3% of patients. At a median follow-up of 28 months, 16 recurrences (21.3%) were recorded, with a 5-year locoregional disease-free survival of 63% . The 5-year disease-free survival and overall survival were 36.7% and 61.6%, respectively. Conclusion: HILP with 1 mg of TNFα is an effective neoadjuvant therapy resulting in a high rate of limb sparing in limb-threatening STS, with acceptable local reactions and negligible systemic toxicity.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration &amp; dosage</subject><subject>Chemotherapy, Cancer, Regional Perfusion - methods</subject><subject>Disease-Free Survival</subject><subject>Doxorubicin - administration &amp; dosage</subject><subject>Extremities - pathology</subject><subject>Female</subject><subject>Humans</subject><subject>Hyperthermia, Induced</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Perfusion</subject><subject>Recurrence</subject><subject>Sarcoma - drug therapy</subject><subject>Soft Tissue Neoplasms - drug therapy</subject><subject>Treatment Outcome</subject><subject>Tumor Necrosis Factor-alpha - administration &amp; dosage</subject><issn>0258-851X</issn><issn>1791-7549</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkM1q3DAUhU1paCZpXyFo0UWzMMi2xpazC2l-DCYTGBe6M9fyla1gS4MkJ5lnzktE0zSQ1YXDd849nC_RKinKJC7WrPwarWi65jFfJ3-PoxPnHinNC0rTb9FxUrKEsZSvote7_Q6tH9HOSpDKmQk89uQBrVycMpo8Kz-SZpmNJfcorHHKkRsQ3tgYpt0IBHRPfpsXY5dOCaWJDGTII41F8DNqT4wktZq7uBkPEmqlB7I10pNGObcg2YIVZoYL0gTb9Uvoo1ALPPgOQZWHSYEOFqHQ7w9ypT0O9l_T2ghjcQhVYfr0MxTZaGEmM-zJr23VVPXm_Ht0JGFy-OP_PY3-3Fw3V3dxvbmtri7reEwz7mPZcY5ZzvKOYQFJWnKaADIBVJYFFpTLklHse8hZADliz_okF10YtC86KrPT6Ow9d7d0M_btzqoZ7L79WD0AP9-BUQ3js7LYuhmmKeBZq57SrE3bLM-yN54ikbU</recordid><startdate>20090301</startdate><enddate>20090301</enddate><creator>Di Filippo, F</creator><creator>Giacomini, P</creator><creator>Rossi, C R</creator><creator>Santinami, M</creator><creator>Garinei, R</creator><creator>Anzà, M</creator><creator>Deraco, M</creator><creator>Botti, C</creator><creator>Perri, P</creator><creator>Cavaliere, F</creator><creator>Di Angelo, P</creator><creator>Sofra, C</creator><creator>Sperduti, I</creator><creator>Pasqualoni, R</creator><creator>Di Filippo, S</creator><creator>Corrias, F</creator><creator>Armenti, A</creator><creator>Ferraresi, V</creator><general>International Institute of Anticancer Research</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20090301</creationdate><title>Hyperthermic Isolated Perfusion with Tumor Necrosis Factor-alpha and Doxorubicin for the Treatment of Limb-Threatening Soft Tissue Sarcoma: The Experience of the Italian Society of Integrated Locoregional Treatment in Oncology (SITILO)</title><author>Di Filippo, F ; Giacomini, P ; Rossi, C R ; Santinami, M ; Garinei, R ; Anzà, M ; Deraco, M ; Botti, C ; Perri, P ; Cavaliere, F ; Di Angelo, P ; Sofra, C ; Sperduti, I ; Pasqualoni, R ; Di Filippo, S ; Corrias, F ; Armenti, A ; Ferraresi, V</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h238t-fb88e3646b4e7a129801ae4ca0f97e708f940edda6488e8eed4d16cb442d7b0f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic Combined Chemotherapy Protocols - administration &amp; dosage</topic><topic>Chemotherapy, Cancer, Regional Perfusion - methods</topic><topic>Disease-Free Survival</topic><topic>Doxorubicin - administration &amp; dosage</topic><topic>Extremities - pathology</topic><topic>Female</topic><topic>Humans</topic><topic>Hyperthermia, Induced</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Perfusion</topic><topic>Recurrence</topic><topic>Sarcoma - drug therapy</topic><topic>Soft Tissue Neoplasms - drug therapy</topic><topic>Treatment Outcome</topic><topic>Tumor Necrosis Factor-alpha - administration &amp; dosage</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Di Filippo, F</creatorcontrib><creatorcontrib>Giacomini, P</creatorcontrib><creatorcontrib>Rossi, C R</creatorcontrib><creatorcontrib>Santinami, M</creatorcontrib><creatorcontrib>Garinei, R</creatorcontrib><creatorcontrib>Anzà, M</creatorcontrib><creatorcontrib>Deraco, M</creatorcontrib><creatorcontrib>Botti, C</creatorcontrib><creatorcontrib>Perri, P</creatorcontrib><creatorcontrib>Cavaliere, F</creatorcontrib><creatorcontrib>Di Angelo, P</creatorcontrib><creatorcontrib>Sofra, C</creatorcontrib><creatorcontrib>Sperduti, I</creatorcontrib><creatorcontrib>Pasqualoni, R</creatorcontrib><creatorcontrib>Di Filippo, S</creatorcontrib><creatorcontrib>Corrias, F</creatorcontrib><creatorcontrib>Armenti, A</creatorcontrib><creatorcontrib>Ferraresi, V</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>In vivo (Athens)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Di Filippo, F</au><au>Giacomini, P</au><au>Rossi, C R</au><au>Santinami, M</au><au>Garinei, R</au><au>Anzà, M</au><au>Deraco, M</au><au>Botti, C</au><au>Perri, P</au><au>Cavaliere, F</au><au>Di Angelo, P</au><au>Sofra, C</au><au>Sperduti, I</au><au>Pasqualoni, R</au><au>Di Filippo, S</au><au>Corrias, F</au><au>Armenti, A</au><au>Ferraresi, V</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hyperthermic Isolated Perfusion with Tumor Necrosis Factor-alpha and Doxorubicin for the Treatment of Limb-Threatening Soft Tissue Sarcoma: The Experience of the Italian Society of Integrated Locoregional Treatment in Oncology (SITILO)</atitle><jtitle>In vivo (Athens)</jtitle><addtitle>In Vivo</addtitle><date>2009-03-01</date><risdate>2009</risdate><volume>23</volume><issue>2</issue><spage>363</spage><pages>363-</pages><issn>0258-851X</issn><eissn>1791-7549</eissn><abstract>Background: Tumor necrosis factor-alpha (TNFα)-based hyperthermic isolated limb perfusion (HILP) is routinely carried out at most oncological institutions in the treatment of locally advanced soft tissue limb sarcoma (STS), employing high TNFα dosages. After a phase I-II study, the SITILO (Italian Society of Integrated Locoregional Therapies in Oncology) centers began to employ the lower dose of 1 mg of TNFα. The aim of this paper is to report on the results obtained in 75 patients with limb-threatening STS treated with a low TNFα dose and doxorubicin (Dx). Patients and Methods: HILP with TNFα (at a dosage of either ≤1 mg or &gt;1 mg) and Dx was administered to 75 patients with limb-threatening STS: 37 males and 38 females; median age 50 years; tumor in the lower and upper limbs in 58 and 17 patients, respectively; primary and recurrent tumors in 45 and 30 patients, respectively. Most tumors (77%) were high grade. Tumor resection was carried out 6 to 8 weeks after HILP. Results: The grade of limb toxicity was mild to moderate in the vast majority of patients (76%). Grades IV and V were observed, but only when high muscle temperatures were recorded and high TNFα dosages were employed. Systemic toxicity was also mild to moderate and there were no postoperative deaths. Complete and partial tumor responses were 34% and 48%, respectively, with an overall response of 82% . Limb sparing surgery was carried out in 85.3% of patients. At a median follow-up of 28 months, 16 recurrences (21.3%) were recorded, with a 5-year locoregional disease-free survival of 63% . The 5-year disease-free survival and overall survival were 36.7% and 61.6%, respectively. Conclusion: HILP with 1 mg of TNFα is an effective neoadjuvant therapy resulting in a high rate of limb sparing in limb-threatening STS, with acceptable local reactions and negligible systemic toxicity.</abstract><cop>Greece</cop><pub>International Institute of Anticancer Research</pub><pmid>19414428</pmid></addata></record>
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ispartof In vivo (Athens), 2009-03, Vol.23 (2), p.363
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source MEDLINE; EZB-FREE-00999 freely available EZB journals
subjects Adolescent
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Chemotherapy, Cancer, Regional Perfusion - methods
Disease-Free Survival
Doxorubicin - administration & dosage
Extremities - pathology
Female
Humans
Hyperthermia, Induced
Male
Middle Aged
Perfusion
Recurrence
Sarcoma - drug therapy
Soft Tissue Neoplasms - drug therapy
Treatment Outcome
Tumor Necrosis Factor-alpha - administration & dosage
title Hyperthermic Isolated Perfusion with Tumor Necrosis Factor-alpha and Doxorubicin for the Treatment of Limb-Threatening Soft Tissue Sarcoma: The Experience of the Italian Society of Integrated Locoregional Treatment in Oncology (SITILO)
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