Factors Predictive of Acute Regional Toxicity After Isolated Limb Infusion with Melphalan and Actinomycin D in Melanoma Patients
Introduction Isolated limb infusion (ILI) with cytotoxic drugs is a low-flow isolated limb perfusion (ILP) performed via percutaneous catheters without oxygenation to treat metastatic melanoma confined to a limb. Response rates and duration of response following ILI are similar to those after ILP. P...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Kroon, Hidde M. [verfasserIn] Moncrieff, Marc [verfasserIn] Kam, Peter C. A. [verfasserIn] Thompson, John F. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2009 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Annals of surgical oncology - Berlin [u.a.] : Springer, 1994, 16(2009), 5 vom: 18. Feb., Seite 1184-1192 |
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| Übergeordnetes Werk: |
volume:16 ; year:2009 ; number:5 ; day:18 ; month:02 ; pages:1184-1192 |
| Links: |
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| DOI / URN: |
10.1245/s10434-009-0323-x |
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| Katalog-ID: |
SPR009931961 |
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| 245 | 1 | 0 | |a Factors Predictive of Acute Regional Toxicity After Isolated Limb Infusion with Melphalan and Actinomycin D in Melanoma Patients |
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| 520 | |a Introduction Isolated limb infusion (ILI) with cytotoxic drugs is a low-flow isolated limb perfusion (ILP) performed via percutaneous catheters without oxygenation to treat metastatic melanoma confined to a limb. Response rates and duration of response following ILI are similar to those after ILP. Previously we have shown that more significant limb toxicity is not associated with a higher response rate or improved patient outcome. In this study we sought to determine factors predicting toxicity following ILI. Methods From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1992 and 2007 were identified. In all patients a cytotoxic combination of melphalan and actinomycin D was used. Drug circulation time was 20–30 min under mild hyperthermic conditions (38–39°C). Limb toxicity was assessed using the Wieberdink scale. Results The average patient age was 74 years (range 29–93 years) and 62% were female. Most patients (134/185) had MD Anderson stage III disease (satellites and in-transit metastases). Toxicity grade I (no reaction) occurred in 3 patients, grade II (slight erythema and edema) in 105 patients, grade III (considerable erythema and edema ± blistering) in 72 patients, and grade IV (threatened or actual compartment syndrome) in 5 patients. No patient developed grade V toxicity (requiring amputation). On univariate analysis high peak and high final melphalan concentrations were found to be predictive factors for grade III/IV limb toxicity as well as the area under the curve of the melphalan concentration. Surprisingly, a greater rise in the $ CO_{2} $ level during the procedure was associated with lower toxicity in the univariate analysis. Increased serum creatine phosphokinase (CK) postoperatively was related to higher toxicity score. In the multivariate analysis high final melphalan concentration and shorter tourniquet time were independent predictive risk factors for developing grade III/IV limb toxicity. Conclusions ILI is a safe alternative to the more invasive and laborious ILP technique to treat melanoma confined to a limb. Regional acute toxicity following ILI is mild to moderate in most patients. Based on the predictive factors found in this series, altering melphalan dose and tourniquet time may allow further reductions in post-ILI toxicity without compromising effectiveness. | ||
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| 700 | 1 | |a Moncrieff, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Kam, Peter C. A. |e verfasserin |4 aut | |
| 700 | 1 | |a Thompson, John F. |e verfasserin |4 aut | |
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10.1245/s10434-009-0323-x doi (DE-627)SPR009931961 (SPR)s10434-009-0323-x-e DE-627 ger DE-627 rakwb eng 610 ASE 44.81 bkl 44.65 bkl Kroon, Hidde M. verfasserin aut Factors Predictive of Acute Regional Toxicity After Isolated Limb Infusion with Melphalan and Actinomycin D in Melanoma Patients 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction Isolated limb infusion (ILI) with cytotoxic drugs is a low-flow isolated limb perfusion (ILP) performed via percutaneous catheters without oxygenation to treat metastatic melanoma confined to a limb. Response rates and duration of response following ILI are similar to those after ILP. Previously we have shown that more significant limb toxicity is not associated with a higher response rate or improved patient outcome. In this study we sought to determine factors predicting toxicity following ILI. Methods From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1992 and 2007 were identified. In all patients a cytotoxic combination of melphalan and actinomycin D was used. Drug circulation time was 20–30 min under mild hyperthermic conditions (38–39°C). Limb toxicity was assessed using the Wieberdink scale. Results The average patient age was 74 years (range 29–93 years) and 62% were female. Most patients (134/185) had MD Anderson stage III disease (satellites and in-transit metastases). Toxicity grade I (no reaction) occurred in 3 patients, grade II (slight erythema and edema) in 105 patients, grade III (considerable erythema and edema ± blistering) in 72 patients, and grade IV (threatened or actual compartment syndrome) in 5 patients. No patient developed grade V toxicity (requiring amputation). On univariate analysis high peak and high final melphalan concentrations were found to be predictive factors for grade III/IV limb toxicity as well as the area under the curve of the melphalan concentration. Surprisingly, a greater rise in the $ CO_{2} $ level during the procedure was associated with lower toxicity in the univariate analysis. Increased serum creatine phosphokinase (CK) postoperatively was related to higher toxicity score. In the multivariate analysis high final melphalan concentration and shorter tourniquet time were independent predictive risk factors for developing grade III/IV limb toxicity. Conclusions ILI is a safe alternative to the more invasive and laborious ILP technique to treat melanoma confined to a limb. Regional acute toxicity following ILI is mild to moderate in most patients. Based on the predictive factors found in this series, altering melphalan dose and tourniquet time may allow further reductions in post-ILI toxicity without compromising effectiveness. Tropisetron (dpeaa)DE-He213 Isolate Limb Perfusion (dpeaa)DE-He213 Isolate Limb Infusion (dpeaa)DE-He213 Limb Volume (dpeaa)DE-He213 Tourniquet Time (dpeaa)DE-He213 Moncrieff, Marc verfasserin aut Kam, Peter C. A. verfasserin aut Thompson, John F. verfasserin aut Enthalten in Annals of surgical oncology Berlin [u.a.] : Springer, 1994 16(2009), 5 vom: 18. Feb., Seite 1184-1192 (DE-627)343969947 (DE-600)2074021-9 1534-4681 nnns volume:16 year:2009 number:5 day:18 month:02 pages:1184-1192 https://dx.doi.org/10.1245/s10434-009-0323-x lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 ASE 44.65 ASE AR 16 2009 5 18 02 1184-1192 |
| spelling |
10.1245/s10434-009-0323-x doi (DE-627)SPR009931961 (SPR)s10434-009-0323-x-e DE-627 ger DE-627 rakwb eng 610 ASE 44.81 bkl 44.65 bkl Kroon, Hidde M. verfasserin aut Factors Predictive of Acute Regional Toxicity After Isolated Limb Infusion with Melphalan and Actinomycin D in Melanoma Patients 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction Isolated limb infusion (ILI) with cytotoxic drugs is a low-flow isolated limb perfusion (ILP) performed via percutaneous catheters without oxygenation to treat metastatic melanoma confined to a limb. Response rates and duration of response following ILI are similar to those after ILP. Previously we have shown that more significant limb toxicity is not associated with a higher response rate or improved patient outcome. In this study we sought to determine factors predicting toxicity following ILI. Methods From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1992 and 2007 were identified. In all patients a cytotoxic combination of melphalan and actinomycin D was used. Drug circulation time was 20–30 min under mild hyperthermic conditions (38–39°C). Limb toxicity was assessed using the Wieberdink scale. Results The average patient age was 74 years (range 29–93 years) and 62% were female. Most patients (134/185) had MD Anderson stage III disease (satellites and in-transit metastases). Toxicity grade I (no reaction) occurred in 3 patients, grade II (slight erythema and edema) in 105 patients, grade III (considerable erythema and edema ± blistering) in 72 patients, and grade IV (threatened or actual compartment syndrome) in 5 patients. No patient developed grade V toxicity (requiring amputation). On univariate analysis high peak and high final melphalan concentrations were found to be predictive factors for grade III/IV limb toxicity as well as the area under the curve of the melphalan concentration. Surprisingly, a greater rise in the $ CO_{2} $ level during the procedure was associated with lower toxicity in the univariate analysis. Increased serum creatine phosphokinase (CK) postoperatively was related to higher toxicity score. In the multivariate analysis high final melphalan concentration and shorter tourniquet time were independent predictive risk factors for developing grade III/IV limb toxicity. Conclusions ILI is a safe alternative to the more invasive and laborious ILP technique to treat melanoma confined to a limb. Regional acute toxicity following ILI is mild to moderate in most patients. Based on the predictive factors found in this series, altering melphalan dose and tourniquet time may allow further reductions in post-ILI toxicity without compromising effectiveness. Tropisetron (dpeaa)DE-He213 Isolate Limb Perfusion (dpeaa)DE-He213 Isolate Limb Infusion (dpeaa)DE-He213 Limb Volume (dpeaa)DE-He213 Tourniquet Time (dpeaa)DE-He213 Moncrieff, Marc verfasserin aut Kam, Peter C. A. verfasserin aut Thompson, John F. verfasserin aut Enthalten in Annals of surgical oncology Berlin [u.a.] : Springer, 1994 16(2009), 5 vom: 18. Feb., Seite 1184-1192 (DE-627)343969947 (DE-600)2074021-9 1534-4681 nnns volume:16 year:2009 number:5 day:18 month:02 pages:1184-1192 https://dx.doi.org/10.1245/s10434-009-0323-x lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 ASE 44.65 ASE AR 16 2009 5 18 02 1184-1192 |
| allfields_unstemmed |
10.1245/s10434-009-0323-x doi (DE-627)SPR009931961 (SPR)s10434-009-0323-x-e DE-627 ger DE-627 rakwb eng 610 ASE 44.81 bkl 44.65 bkl Kroon, Hidde M. verfasserin aut Factors Predictive of Acute Regional Toxicity After Isolated Limb Infusion with Melphalan and Actinomycin D in Melanoma Patients 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction Isolated limb infusion (ILI) with cytotoxic drugs is a low-flow isolated limb perfusion (ILP) performed via percutaneous catheters without oxygenation to treat metastatic melanoma confined to a limb. Response rates and duration of response following ILI are similar to those after ILP. Previously we have shown that more significant limb toxicity is not associated with a higher response rate or improved patient outcome. In this study we sought to determine factors predicting toxicity following ILI. Methods From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1992 and 2007 were identified. In all patients a cytotoxic combination of melphalan and actinomycin D was used. Drug circulation time was 20–30 min under mild hyperthermic conditions (38–39°C). Limb toxicity was assessed using the Wieberdink scale. Results The average patient age was 74 years (range 29–93 years) and 62% were female. Most patients (134/185) had MD Anderson stage III disease (satellites and in-transit metastases). Toxicity grade I (no reaction) occurred in 3 patients, grade II (slight erythema and edema) in 105 patients, grade III (considerable erythema and edema ± blistering) in 72 patients, and grade IV (threatened or actual compartment syndrome) in 5 patients. No patient developed grade V toxicity (requiring amputation). On univariate analysis high peak and high final melphalan concentrations were found to be predictive factors for grade III/IV limb toxicity as well as the area under the curve of the melphalan concentration. Surprisingly, a greater rise in the $ CO_{2} $ level during the procedure was associated with lower toxicity in the univariate analysis. Increased serum creatine phosphokinase (CK) postoperatively was related to higher toxicity score. In the multivariate analysis high final melphalan concentration and shorter tourniquet time were independent predictive risk factors for developing grade III/IV limb toxicity. Conclusions ILI is a safe alternative to the more invasive and laborious ILP technique to treat melanoma confined to a limb. Regional acute toxicity following ILI is mild to moderate in most patients. Based on the predictive factors found in this series, altering melphalan dose and tourniquet time may allow further reductions in post-ILI toxicity without compromising effectiveness. Tropisetron (dpeaa)DE-He213 Isolate Limb Perfusion (dpeaa)DE-He213 Isolate Limb Infusion (dpeaa)DE-He213 Limb Volume (dpeaa)DE-He213 Tourniquet Time (dpeaa)DE-He213 Moncrieff, Marc verfasserin aut Kam, Peter C. A. verfasserin aut Thompson, John F. verfasserin aut Enthalten in Annals of surgical oncology Berlin [u.a.] : Springer, 1994 16(2009), 5 vom: 18. Feb., Seite 1184-1192 (DE-627)343969947 (DE-600)2074021-9 1534-4681 nnns volume:16 year:2009 number:5 day:18 month:02 pages:1184-1192 https://dx.doi.org/10.1245/s10434-009-0323-x lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 ASE 44.65 ASE AR 16 2009 5 18 02 1184-1192 |
| allfieldsGer |
10.1245/s10434-009-0323-x doi (DE-627)SPR009931961 (SPR)s10434-009-0323-x-e DE-627 ger DE-627 rakwb eng 610 ASE 44.81 bkl 44.65 bkl Kroon, Hidde M. verfasserin aut Factors Predictive of Acute Regional Toxicity After Isolated Limb Infusion with Melphalan and Actinomycin D in Melanoma Patients 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction Isolated limb infusion (ILI) with cytotoxic drugs is a low-flow isolated limb perfusion (ILP) performed via percutaneous catheters without oxygenation to treat metastatic melanoma confined to a limb. Response rates and duration of response following ILI are similar to those after ILP. Previously we have shown that more significant limb toxicity is not associated with a higher response rate or improved patient outcome. In this study we sought to determine factors predicting toxicity following ILI. Methods From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1992 and 2007 were identified. In all patients a cytotoxic combination of melphalan and actinomycin D was used. Drug circulation time was 20–30 min under mild hyperthermic conditions (38–39°C). Limb toxicity was assessed using the Wieberdink scale. Results The average patient age was 74 years (range 29–93 years) and 62% were female. Most patients (134/185) had MD Anderson stage III disease (satellites and in-transit metastases). Toxicity grade I (no reaction) occurred in 3 patients, grade II (slight erythema and edema) in 105 patients, grade III (considerable erythema and edema ± blistering) in 72 patients, and grade IV (threatened or actual compartment syndrome) in 5 patients. No patient developed grade V toxicity (requiring amputation). On univariate analysis high peak and high final melphalan concentrations were found to be predictive factors for grade III/IV limb toxicity as well as the area under the curve of the melphalan concentration. Surprisingly, a greater rise in the $ CO_{2} $ level during the procedure was associated with lower toxicity in the univariate analysis. Increased serum creatine phosphokinase (CK) postoperatively was related to higher toxicity score. In the multivariate analysis high final melphalan concentration and shorter tourniquet time were independent predictive risk factors for developing grade III/IV limb toxicity. Conclusions ILI is a safe alternative to the more invasive and laborious ILP technique to treat melanoma confined to a limb. Regional acute toxicity following ILI is mild to moderate in most patients. Based on the predictive factors found in this series, altering melphalan dose and tourniquet time may allow further reductions in post-ILI toxicity without compromising effectiveness. Tropisetron (dpeaa)DE-He213 Isolate Limb Perfusion (dpeaa)DE-He213 Isolate Limb Infusion (dpeaa)DE-He213 Limb Volume (dpeaa)DE-He213 Tourniquet Time (dpeaa)DE-He213 Moncrieff, Marc verfasserin aut Kam, Peter C. A. verfasserin aut Thompson, John F. verfasserin aut Enthalten in Annals of surgical oncology Berlin [u.a.] : Springer, 1994 16(2009), 5 vom: 18. Feb., Seite 1184-1192 (DE-627)343969947 (DE-600)2074021-9 1534-4681 nnns volume:16 year:2009 number:5 day:18 month:02 pages:1184-1192 https://dx.doi.org/10.1245/s10434-009-0323-x lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 ASE 44.65 ASE AR 16 2009 5 18 02 1184-1192 |
| allfieldsSound |
10.1245/s10434-009-0323-x doi (DE-627)SPR009931961 (SPR)s10434-009-0323-x-e DE-627 ger DE-627 rakwb eng 610 ASE 44.81 bkl 44.65 bkl Kroon, Hidde M. verfasserin aut Factors Predictive of Acute Regional Toxicity After Isolated Limb Infusion with Melphalan and Actinomycin D in Melanoma Patients 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction Isolated limb infusion (ILI) with cytotoxic drugs is a low-flow isolated limb perfusion (ILP) performed via percutaneous catheters without oxygenation to treat metastatic melanoma confined to a limb. Response rates and duration of response following ILI are similar to those after ILP. Previously we have shown that more significant limb toxicity is not associated with a higher response rate or improved patient outcome. In this study we sought to determine factors predicting toxicity following ILI. Methods From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1992 and 2007 were identified. In all patients a cytotoxic combination of melphalan and actinomycin D was used. Drug circulation time was 20–30 min under mild hyperthermic conditions (38–39°C). Limb toxicity was assessed using the Wieberdink scale. Results The average patient age was 74 years (range 29–93 years) and 62% were female. Most patients (134/185) had MD Anderson stage III disease (satellites and in-transit metastases). Toxicity grade I (no reaction) occurred in 3 patients, grade II (slight erythema and edema) in 105 patients, grade III (considerable erythema and edema ± blistering) in 72 patients, and grade IV (threatened or actual compartment syndrome) in 5 patients. No patient developed grade V toxicity (requiring amputation). On univariate analysis high peak and high final melphalan concentrations were found to be predictive factors for grade III/IV limb toxicity as well as the area under the curve of the melphalan concentration. Surprisingly, a greater rise in the $ CO_{2} $ level during the procedure was associated with lower toxicity in the univariate analysis. Increased serum creatine phosphokinase (CK) postoperatively was related to higher toxicity score. In the multivariate analysis high final melphalan concentration and shorter tourniquet time were independent predictive risk factors for developing grade III/IV limb toxicity. Conclusions ILI is a safe alternative to the more invasive and laborious ILP technique to treat melanoma confined to a limb. Regional acute toxicity following ILI is mild to moderate in most patients. Based on the predictive factors found in this series, altering melphalan dose and tourniquet time may allow further reductions in post-ILI toxicity without compromising effectiveness. Tropisetron (dpeaa)DE-He213 Isolate Limb Perfusion (dpeaa)DE-He213 Isolate Limb Infusion (dpeaa)DE-He213 Limb Volume (dpeaa)DE-He213 Tourniquet Time (dpeaa)DE-He213 Moncrieff, Marc verfasserin aut Kam, Peter C. A. verfasserin aut Thompson, John F. verfasserin aut Enthalten in Annals of surgical oncology Berlin [u.a.] : Springer, 1994 16(2009), 5 vom: 18. Feb., Seite 1184-1192 (DE-627)343969947 (DE-600)2074021-9 1534-4681 nnns volume:16 year:2009 number:5 day:18 month:02 pages:1184-1192 https://dx.doi.org/10.1245/s10434-009-0323-x lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 ASE 44.65 ASE AR 16 2009 5 18 02 1184-1192 |
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English |
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Enthalten in Annals of surgical oncology 16(2009), 5 vom: 18. Feb., Seite 1184-1192 volume:16 year:2009 number:5 day:18 month:02 pages:1184-1192 |
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Enthalten in Annals of surgical oncology 16(2009), 5 vom: 18. Feb., Seite 1184-1192 volume:16 year:2009 number:5 day:18 month:02 pages:1184-1192 |
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Tropisetron Isolate Limb Perfusion Isolate Limb Infusion Limb Volume Tourniquet Time |
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Kroon, Hidde M. @@aut@@ Moncrieff, Marc @@aut@@ Kam, Peter C. A. @@aut@@ Thompson, John F. @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR009931961</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519153800.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201005s2009 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1245/s10434-009-0323-x</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR009931961</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s10434-009-0323-x-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.81</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.65</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Kroon, Hidde M.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Factors Predictive of Acute Regional Toxicity After Isolated Limb Infusion with Melphalan and Actinomycin D in Melanoma Patients</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2009</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Introduction Isolated limb infusion (ILI) with cytotoxic drugs is a low-flow isolated limb perfusion (ILP) performed via percutaneous catheters without oxygenation to treat metastatic melanoma confined to a limb. Response rates and duration of response following ILI are similar to those after ILP. Previously we have shown that more significant limb toxicity is not associated with a higher response rate or improved patient outcome. In this study we sought to determine factors predicting toxicity following ILI. Methods From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1992 and 2007 were identified. In all patients a cytotoxic combination of melphalan and actinomycin D was used. Drug circulation time was 20–30 min under mild hyperthermic conditions (38–39°C). Limb toxicity was assessed using the Wieberdink scale. Results The average patient age was 74 years (range 29–93 years) and 62% were female. Most patients (134/185) had MD Anderson stage III disease (satellites and in-transit metastases). Toxicity grade I (no reaction) occurred in 3 patients, grade II (slight erythema and edema) in 105 patients, grade III (considerable erythema and edema ± blistering) in 72 patients, and grade IV (threatened or actual compartment syndrome) in 5 patients. No patient developed grade V toxicity (requiring amputation). On univariate analysis high peak and high final melphalan concentrations were found to be predictive factors for grade III/IV limb toxicity as well as the area under the curve of the melphalan concentration. Surprisingly, a greater rise in the $ CO_{2} $ level during the procedure was associated with lower toxicity in the univariate analysis. Increased serum creatine phosphokinase (CK) postoperatively was related to higher toxicity score. In the multivariate analysis high final melphalan concentration and shorter tourniquet time were independent predictive risk factors for developing grade III/IV limb toxicity. Conclusions ILI is a safe alternative to the more invasive and laborious ILP technique to treat melanoma confined to a limb. Regional acute toxicity following ILI is mild to moderate in most patients. 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Kroon, Hidde M. |
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Kroon, Hidde M. ddc 610 bkl 44.81 bkl 44.65 misc Tropisetron misc Isolate Limb Perfusion misc Isolate Limb Infusion misc Limb Volume misc Tourniquet Time Factors Predictive of Acute Regional Toxicity After Isolated Limb Infusion with Melphalan and Actinomycin D in Melanoma Patients |
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610 ASE 44.81 bkl 44.65 bkl Factors Predictive of Acute Regional Toxicity After Isolated Limb Infusion with Melphalan and Actinomycin D in Melanoma Patients Tropisetron (dpeaa)DE-He213 Isolate Limb Perfusion (dpeaa)DE-He213 Isolate Limb Infusion (dpeaa)DE-He213 Limb Volume (dpeaa)DE-He213 Tourniquet Time (dpeaa)DE-He213 |
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ddc 610 bkl 44.81 bkl 44.65 misc Tropisetron misc Isolate Limb Perfusion misc Isolate Limb Infusion misc Limb Volume misc Tourniquet Time |
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ddc 610 bkl 44.81 bkl 44.65 misc Tropisetron misc Isolate Limb Perfusion misc Isolate Limb Infusion misc Limb Volume misc Tourniquet Time |
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Factors Predictive of Acute Regional Toxicity After Isolated Limb Infusion with Melphalan and Actinomycin D in Melanoma Patients |
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Factors Predictive of Acute Regional Toxicity After Isolated Limb Infusion with Melphalan and Actinomycin D in Melanoma Patients |
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Kroon, Hidde M. |
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Annals of surgical oncology |
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Kroon, Hidde M. Moncrieff, Marc Kam, Peter C. A. Thompson, John F. |
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Kroon, Hidde M. |
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factors predictive of acute regional toxicity after isolated limb infusion with melphalan and actinomycin d in melanoma patients |
| title_auth |
Factors Predictive of Acute Regional Toxicity After Isolated Limb Infusion with Melphalan and Actinomycin D in Melanoma Patients |
| abstract |
Introduction Isolated limb infusion (ILI) with cytotoxic drugs is a low-flow isolated limb perfusion (ILP) performed via percutaneous catheters without oxygenation to treat metastatic melanoma confined to a limb. Response rates and duration of response following ILI are similar to those after ILP. Previously we have shown that more significant limb toxicity is not associated with a higher response rate or improved patient outcome. In this study we sought to determine factors predicting toxicity following ILI. Methods From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1992 and 2007 were identified. In all patients a cytotoxic combination of melphalan and actinomycin D was used. Drug circulation time was 20–30 min under mild hyperthermic conditions (38–39°C). Limb toxicity was assessed using the Wieberdink scale. Results The average patient age was 74 years (range 29–93 years) and 62% were female. Most patients (134/185) had MD Anderson stage III disease (satellites and in-transit metastases). Toxicity grade I (no reaction) occurred in 3 patients, grade II (slight erythema and edema) in 105 patients, grade III (considerable erythema and edema ± blistering) in 72 patients, and grade IV (threatened or actual compartment syndrome) in 5 patients. No patient developed grade V toxicity (requiring amputation). On univariate analysis high peak and high final melphalan concentrations were found to be predictive factors for grade III/IV limb toxicity as well as the area under the curve of the melphalan concentration. Surprisingly, a greater rise in the $ CO_{2} $ level during the procedure was associated with lower toxicity in the univariate analysis. Increased serum creatine phosphokinase (CK) postoperatively was related to higher toxicity score. In the multivariate analysis high final melphalan concentration and shorter tourniquet time were independent predictive risk factors for developing grade III/IV limb toxicity. Conclusions ILI is a safe alternative to the more invasive and laborious ILP technique to treat melanoma confined to a limb. Regional acute toxicity following ILI is mild to moderate in most patients. Based on the predictive factors found in this series, altering melphalan dose and tourniquet time may allow further reductions in post-ILI toxicity without compromising effectiveness. |
| abstractGer |
Introduction Isolated limb infusion (ILI) with cytotoxic drugs is a low-flow isolated limb perfusion (ILP) performed via percutaneous catheters without oxygenation to treat metastatic melanoma confined to a limb. Response rates and duration of response following ILI are similar to those after ILP. Previously we have shown that more significant limb toxicity is not associated with a higher response rate or improved patient outcome. In this study we sought to determine factors predicting toxicity following ILI. Methods From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1992 and 2007 were identified. In all patients a cytotoxic combination of melphalan and actinomycin D was used. Drug circulation time was 20–30 min under mild hyperthermic conditions (38–39°C). Limb toxicity was assessed using the Wieberdink scale. Results The average patient age was 74 years (range 29–93 years) and 62% were female. Most patients (134/185) had MD Anderson stage III disease (satellites and in-transit metastases). Toxicity grade I (no reaction) occurred in 3 patients, grade II (slight erythema and edema) in 105 patients, grade III (considerable erythema and edema ± blistering) in 72 patients, and grade IV (threatened or actual compartment syndrome) in 5 patients. No patient developed grade V toxicity (requiring amputation). On univariate analysis high peak and high final melphalan concentrations were found to be predictive factors for grade III/IV limb toxicity as well as the area under the curve of the melphalan concentration. Surprisingly, a greater rise in the $ CO_{2} $ level during the procedure was associated with lower toxicity in the univariate analysis. Increased serum creatine phosphokinase (CK) postoperatively was related to higher toxicity score. In the multivariate analysis high final melphalan concentration and shorter tourniquet time were independent predictive risk factors for developing grade III/IV limb toxicity. Conclusions ILI is a safe alternative to the more invasive and laborious ILP technique to treat melanoma confined to a limb. Regional acute toxicity following ILI is mild to moderate in most patients. Based on the predictive factors found in this series, altering melphalan dose and tourniquet time may allow further reductions in post-ILI toxicity without compromising effectiveness. |
| abstract_unstemmed |
Introduction Isolated limb infusion (ILI) with cytotoxic drugs is a low-flow isolated limb perfusion (ILP) performed via percutaneous catheters without oxygenation to treat metastatic melanoma confined to a limb. Response rates and duration of response following ILI are similar to those after ILP. Previously we have shown that more significant limb toxicity is not associated with a higher response rate or improved patient outcome. In this study we sought to determine factors predicting toxicity following ILI. Methods From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1992 and 2007 were identified. In all patients a cytotoxic combination of melphalan and actinomycin D was used. Drug circulation time was 20–30 min under mild hyperthermic conditions (38–39°C). Limb toxicity was assessed using the Wieberdink scale. Results The average patient age was 74 years (range 29–93 years) and 62% were female. Most patients (134/185) had MD Anderson stage III disease (satellites and in-transit metastases). Toxicity grade I (no reaction) occurred in 3 patients, grade II (slight erythema and edema) in 105 patients, grade III (considerable erythema and edema ± blistering) in 72 patients, and grade IV (threatened or actual compartment syndrome) in 5 patients. No patient developed grade V toxicity (requiring amputation). On univariate analysis high peak and high final melphalan concentrations were found to be predictive factors for grade III/IV limb toxicity as well as the area under the curve of the melphalan concentration. Surprisingly, a greater rise in the $ CO_{2} $ level during the procedure was associated with lower toxicity in the univariate analysis. Increased serum creatine phosphokinase (CK) postoperatively was related to higher toxicity score. In the multivariate analysis high final melphalan concentration and shorter tourniquet time were independent predictive risk factors for developing grade III/IV limb toxicity. Conclusions ILI is a safe alternative to the more invasive and laborious ILP technique to treat melanoma confined to a limb. Regional acute toxicity following ILI is mild to moderate in most patients. Based on the predictive factors found in this series, altering melphalan dose and tourniquet time may allow further reductions in post-ILI toxicity without compromising effectiveness. |
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Factors Predictive of Acute Regional Toxicity After Isolated Limb Infusion with Melphalan and Actinomycin D in Melanoma Patients |
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| score |
7.400839 |