Thalidomide and celecoxib as potential modulators of irinotecan’s activity in cancer patients
Abstract Purpose: Nuclear factor-κB (NF-κB) activation induces resistance to irinotecan. Preclinically, thalidomide and COX-2 inhibitors reduce NF-κB activation. We tested the feasibility of combining irinotecan with thalidomide and thalidomide/celecoxib in patients with refractory malignancies. Pat...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Villalona-Calero, Miguel [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2006 |
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| Schlagwörter: |
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| Anmerkung: |
© Springer-Verlag 2006 |
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| Übergeordnetes Werk: |
Enthalten in: Cancer chemotherapy and pharmacology - Berlin : Springer, 1978, 59(2006), 1 vom: 10. Mai, Seite 23-33 |
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| Übergeordnetes Werk: |
volume:59 ; year:2006 ; number:1 ; day:10 ; month:05 ; pages:23-33 |
| Links: |
|---|
| DOI / URN: |
10.1007/s00280-006-0249-y |
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| Katalog-ID: |
SPR003586375 |
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| 100 | 1 | |a Villalona-Calero, Miguel |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Thalidomide and celecoxib as potential modulators of irinotecan’s activity in cancer patients |
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| 520 | |a Abstract Purpose: Nuclear factor-κB (NF-κB) activation induces resistance to irinotecan. Preclinically, thalidomide and COX-2 inhibitors reduce NF-κB activation. We tested the feasibility of combining irinotecan with thalidomide and thalidomide/celecoxib in patients with refractory malignancies. Patients/methods: The study was conducted in two parts. First, the optimal dose of thalidomide (400 or 200 mg daily) in combination with irinotecan 125 mg/$ m^{2} $ days 1 and 8 every 3 weeks was determined. In the second part, celecoxib 400 mg twice-daily was added to irinotecan/thalidomide. Pharmacokinetics of irinotecan and thalidomide alone or concurrently were evaluated. Tumor necrosis factor alpha, beta-fibroblast growth factor, and NF-κB activation were measured in blood mononuclear cells (PBMC). No CYP450 enzyme inducers/inhibitors were allowed. Results: Thirty-six patients were enrolled: Eleven received thalidomide 400 mg, 13 thalidomide 200 mg and 12 thalidomide 400 mg and celecoxib, with irinotecan. For the two-drug combination, there was a higher rate of moderate/severe diarrhea/myelosuppression with thalidomide 200 mg. Thus thalidomide 400 mg was combined with celecoxib. The triple combination resulted in similar toxicity as the doublet with the lower thalidomide dose. Concurrent administration of irinotecan/thalidomide did not influence pharmacokinetics. Anti-tumor responses occurred in two patients and prolonged stabilization in eight others. NF-κB activation increased over time. Patients experiencing tumor response or prolonged stabilization had lower NF-κB activation, albeit not statistically significant (P = 0.124). Conclusions: The combination of thalidomide/irinotecan is safe and devoid of PK interactions. Thalidomide 400 mg appeared more suitable for combination, whereas the addition of celecoxib did not improve tolerability. Tumor-specific studies in patients with lesser prior treatment will be necessary to establish the therapeutic impact of the combinations. | ||
| 650 | 4 | |a Irinotecan |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Celecoxib |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Thalidomide |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Dose Limit Toxicity |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Nonhematologic Toxicity |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Schaaf, Larry |4 aut | |
| 700 | 1 | |a Phillips, Gary |4 aut | |
| 700 | 1 | |a Otterson, Gregory |4 aut | |
| 700 | 1 | |a Panico, Kevin |4 aut | |
| 700 | 1 | |a Duan, Wenrui |4 aut | |
| 700 | 1 | |a Kleiber, Barbara |4 aut | |
| 700 | 1 | |a Shah, Manisha |4 aut | |
| 700 | 1 | |a Young, Donn |4 aut | |
| 700 | 1 | |a Wu, Wan-Hong |4 aut | |
| 700 | 1 | |a Kuhn, John |4 aut | |
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10.1007/s00280-006-0249-y doi (DE-627)SPR003586375 (SPR)s00280-006-0249-y-e DE-627 ger DE-627 rakwb eng Villalona-Calero, Miguel verfasserin aut Thalidomide and celecoxib as potential modulators of irinotecan’s activity in cancer patients 2006 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2006 Abstract Purpose: Nuclear factor-κB (NF-κB) activation induces resistance to irinotecan. Preclinically, thalidomide and COX-2 inhibitors reduce NF-κB activation. We tested the feasibility of combining irinotecan with thalidomide and thalidomide/celecoxib in patients with refractory malignancies. Patients/methods: The study was conducted in two parts. First, the optimal dose of thalidomide (400 or 200 mg daily) in combination with irinotecan 125 mg/$ m^{2} $ days 1 and 8 every 3 weeks was determined. In the second part, celecoxib 400 mg twice-daily was added to irinotecan/thalidomide. Pharmacokinetics of irinotecan and thalidomide alone or concurrently were evaluated. Tumor necrosis factor alpha, beta-fibroblast growth factor, and NF-κB activation were measured in blood mononuclear cells (PBMC). No CYP450 enzyme inducers/inhibitors were allowed. Results: Thirty-six patients were enrolled: Eleven received thalidomide 400 mg, 13 thalidomide 200 mg and 12 thalidomide 400 mg and celecoxib, with irinotecan. For the two-drug combination, there was a higher rate of moderate/severe diarrhea/myelosuppression with thalidomide 200 mg. Thus thalidomide 400 mg was combined with celecoxib. The triple combination resulted in similar toxicity as the doublet with the lower thalidomide dose. Concurrent administration of irinotecan/thalidomide did not influence pharmacokinetics. Anti-tumor responses occurred in two patients and prolonged stabilization in eight others. NF-κB activation increased over time. Patients experiencing tumor response or prolonged stabilization had lower NF-κB activation, albeit not statistically significant (P = 0.124). Conclusions: The combination of thalidomide/irinotecan is safe and devoid of PK interactions. Thalidomide 400 mg appeared more suitable for combination, whereas the addition of celecoxib did not improve tolerability. Tumor-specific studies in patients with lesser prior treatment will be necessary to establish the therapeutic impact of the combinations. Irinotecan (dpeaa)DE-He213 Celecoxib (dpeaa)DE-He213 Thalidomide (dpeaa)DE-He213 Dose Limit Toxicity (dpeaa)DE-He213 Nonhematologic Toxicity (dpeaa)DE-He213 Schaaf, Larry aut Phillips, Gary aut Otterson, Gregory aut Panico, Kevin aut Duan, Wenrui aut Kleiber, Barbara aut Shah, Manisha aut Young, Donn aut Wu, Wan-Hong aut Kuhn, John aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 59(2006), 1 vom: 10. Mai, Seite 23-33 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:59 year:2006 number:1 day:10 month:05 pages:23-33 https://dx.doi.org/10.1007/s00280-006-0249-y 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_267 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 AR 59 2006 1 10 05 23-33 |
| spelling |
10.1007/s00280-006-0249-y doi (DE-627)SPR003586375 (SPR)s00280-006-0249-y-e DE-627 ger DE-627 rakwb eng Villalona-Calero, Miguel verfasserin aut Thalidomide and celecoxib as potential modulators of irinotecan’s activity in cancer patients 2006 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2006 Abstract Purpose: Nuclear factor-κB (NF-κB) activation induces resistance to irinotecan. Preclinically, thalidomide and COX-2 inhibitors reduce NF-κB activation. We tested the feasibility of combining irinotecan with thalidomide and thalidomide/celecoxib in patients with refractory malignancies. Patients/methods: The study was conducted in two parts. First, the optimal dose of thalidomide (400 or 200 mg daily) in combination with irinotecan 125 mg/$ m^{2} $ days 1 and 8 every 3 weeks was determined. In the second part, celecoxib 400 mg twice-daily was added to irinotecan/thalidomide. Pharmacokinetics of irinotecan and thalidomide alone or concurrently were evaluated. Tumor necrosis factor alpha, beta-fibroblast growth factor, and NF-κB activation were measured in blood mononuclear cells (PBMC). No CYP450 enzyme inducers/inhibitors were allowed. Results: Thirty-six patients were enrolled: Eleven received thalidomide 400 mg, 13 thalidomide 200 mg and 12 thalidomide 400 mg and celecoxib, with irinotecan. For the two-drug combination, there was a higher rate of moderate/severe diarrhea/myelosuppression with thalidomide 200 mg. Thus thalidomide 400 mg was combined with celecoxib. The triple combination resulted in similar toxicity as the doublet with the lower thalidomide dose. Concurrent administration of irinotecan/thalidomide did not influence pharmacokinetics. Anti-tumor responses occurred in two patients and prolonged stabilization in eight others. NF-κB activation increased over time. Patients experiencing tumor response or prolonged stabilization had lower NF-κB activation, albeit not statistically significant (P = 0.124). Conclusions: The combination of thalidomide/irinotecan is safe and devoid of PK interactions. Thalidomide 400 mg appeared more suitable for combination, whereas the addition of celecoxib did not improve tolerability. Tumor-specific studies in patients with lesser prior treatment will be necessary to establish the therapeutic impact of the combinations. Irinotecan (dpeaa)DE-He213 Celecoxib (dpeaa)DE-He213 Thalidomide (dpeaa)DE-He213 Dose Limit Toxicity (dpeaa)DE-He213 Nonhematologic Toxicity (dpeaa)DE-He213 Schaaf, Larry aut Phillips, Gary aut Otterson, Gregory aut Panico, Kevin aut Duan, Wenrui aut Kleiber, Barbara aut Shah, Manisha aut Young, Donn aut Wu, Wan-Hong aut Kuhn, John aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 59(2006), 1 vom: 10. Mai, Seite 23-33 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:59 year:2006 number:1 day:10 month:05 pages:23-33 https://dx.doi.org/10.1007/s00280-006-0249-y 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_267 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 AR 59 2006 1 10 05 23-33 |
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10.1007/s00280-006-0249-y doi (DE-627)SPR003586375 (SPR)s00280-006-0249-y-e DE-627 ger DE-627 rakwb eng Villalona-Calero, Miguel verfasserin aut Thalidomide and celecoxib as potential modulators of irinotecan’s activity in cancer patients 2006 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2006 Abstract Purpose: Nuclear factor-κB (NF-κB) activation induces resistance to irinotecan. Preclinically, thalidomide and COX-2 inhibitors reduce NF-κB activation. We tested the feasibility of combining irinotecan with thalidomide and thalidomide/celecoxib in patients with refractory malignancies. Patients/methods: The study was conducted in two parts. First, the optimal dose of thalidomide (400 or 200 mg daily) in combination with irinotecan 125 mg/$ m^{2} $ days 1 and 8 every 3 weeks was determined. In the second part, celecoxib 400 mg twice-daily was added to irinotecan/thalidomide. Pharmacokinetics of irinotecan and thalidomide alone or concurrently were evaluated. Tumor necrosis factor alpha, beta-fibroblast growth factor, and NF-κB activation were measured in blood mononuclear cells (PBMC). No CYP450 enzyme inducers/inhibitors were allowed. Results: Thirty-six patients were enrolled: Eleven received thalidomide 400 mg, 13 thalidomide 200 mg and 12 thalidomide 400 mg and celecoxib, with irinotecan. For the two-drug combination, there was a higher rate of moderate/severe diarrhea/myelosuppression with thalidomide 200 mg. Thus thalidomide 400 mg was combined with celecoxib. The triple combination resulted in similar toxicity as the doublet with the lower thalidomide dose. Concurrent administration of irinotecan/thalidomide did not influence pharmacokinetics. Anti-tumor responses occurred in two patients and prolonged stabilization in eight others. NF-κB activation increased over time. Patients experiencing tumor response or prolonged stabilization had lower NF-κB activation, albeit not statistically significant (P = 0.124). Conclusions: The combination of thalidomide/irinotecan is safe and devoid of PK interactions. Thalidomide 400 mg appeared more suitable for combination, whereas the addition of celecoxib did not improve tolerability. Tumor-specific studies in patients with lesser prior treatment will be necessary to establish the therapeutic impact of the combinations. Irinotecan (dpeaa)DE-He213 Celecoxib (dpeaa)DE-He213 Thalidomide (dpeaa)DE-He213 Dose Limit Toxicity (dpeaa)DE-He213 Nonhematologic Toxicity (dpeaa)DE-He213 Schaaf, Larry aut Phillips, Gary aut Otterson, Gregory aut Panico, Kevin aut Duan, Wenrui aut Kleiber, Barbara aut Shah, Manisha aut Young, Donn aut Wu, Wan-Hong aut Kuhn, John aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 59(2006), 1 vom: 10. Mai, Seite 23-33 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:59 year:2006 number:1 day:10 month:05 pages:23-33 https://dx.doi.org/10.1007/s00280-006-0249-y 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_267 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 AR 59 2006 1 10 05 23-33 |
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10.1007/s00280-006-0249-y doi (DE-627)SPR003586375 (SPR)s00280-006-0249-y-e DE-627 ger DE-627 rakwb eng Villalona-Calero, Miguel verfasserin aut Thalidomide and celecoxib as potential modulators of irinotecan’s activity in cancer patients 2006 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2006 Abstract Purpose: Nuclear factor-κB (NF-κB) activation induces resistance to irinotecan. Preclinically, thalidomide and COX-2 inhibitors reduce NF-κB activation. We tested the feasibility of combining irinotecan with thalidomide and thalidomide/celecoxib in patients with refractory malignancies. Patients/methods: The study was conducted in two parts. First, the optimal dose of thalidomide (400 or 200 mg daily) in combination with irinotecan 125 mg/$ m^{2} $ days 1 and 8 every 3 weeks was determined. In the second part, celecoxib 400 mg twice-daily was added to irinotecan/thalidomide. Pharmacokinetics of irinotecan and thalidomide alone or concurrently were evaluated. Tumor necrosis factor alpha, beta-fibroblast growth factor, and NF-κB activation were measured in blood mononuclear cells (PBMC). No CYP450 enzyme inducers/inhibitors were allowed. Results: Thirty-six patients were enrolled: Eleven received thalidomide 400 mg, 13 thalidomide 200 mg and 12 thalidomide 400 mg and celecoxib, with irinotecan. For the two-drug combination, there was a higher rate of moderate/severe diarrhea/myelosuppression with thalidomide 200 mg. Thus thalidomide 400 mg was combined with celecoxib. The triple combination resulted in similar toxicity as the doublet with the lower thalidomide dose. Concurrent administration of irinotecan/thalidomide did not influence pharmacokinetics. Anti-tumor responses occurred in two patients and prolonged stabilization in eight others. NF-κB activation increased over time. Patients experiencing tumor response or prolonged stabilization had lower NF-κB activation, albeit not statistically significant (P = 0.124). Conclusions: The combination of thalidomide/irinotecan is safe and devoid of PK interactions. Thalidomide 400 mg appeared more suitable for combination, whereas the addition of celecoxib did not improve tolerability. Tumor-specific studies in patients with lesser prior treatment will be necessary to establish the therapeutic impact of the combinations. Irinotecan (dpeaa)DE-He213 Celecoxib (dpeaa)DE-He213 Thalidomide (dpeaa)DE-He213 Dose Limit Toxicity (dpeaa)DE-He213 Nonhematologic Toxicity (dpeaa)DE-He213 Schaaf, Larry aut Phillips, Gary aut Otterson, Gregory aut Panico, Kevin aut Duan, Wenrui aut Kleiber, Barbara aut Shah, Manisha aut Young, Donn aut Wu, Wan-Hong aut Kuhn, John aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 59(2006), 1 vom: 10. Mai, Seite 23-33 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:59 year:2006 number:1 day:10 month:05 pages:23-33 https://dx.doi.org/10.1007/s00280-006-0249-y 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_267 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 AR 59 2006 1 10 05 23-33 |
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10.1007/s00280-006-0249-y doi (DE-627)SPR003586375 (SPR)s00280-006-0249-y-e DE-627 ger DE-627 rakwb eng Villalona-Calero, Miguel verfasserin aut Thalidomide and celecoxib as potential modulators of irinotecan’s activity in cancer patients 2006 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2006 Abstract Purpose: Nuclear factor-κB (NF-κB) activation induces resistance to irinotecan. Preclinically, thalidomide and COX-2 inhibitors reduce NF-κB activation. We tested the feasibility of combining irinotecan with thalidomide and thalidomide/celecoxib in patients with refractory malignancies. Patients/methods: The study was conducted in two parts. First, the optimal dose of thalidomide (400 or 200 mg daily) in combination with irinotecan 125 mg/$ m^{2} $ days 1 and 8 every 3 weeks was determined. In the second part, celecoxib 400 mg twice-daily was added to irinotecan/thalidomide. Pharmacokinetics of irinotecan and thalidomide alone or concurrently were evaluated. Tumor necrosis factor alpha, beta-fibroblast growth factor, and NF-κB activation were measured in blood mononuclear cells (PBMC). No CYP450 enzyme inducers/inhibitors were allowed. Results: Thirty-six patients were enrolled: Eleven received thalidomide 400 mg, 13 thalidomide 200 mg and 12 thalidomide 400 mg and celecoxib, with irinotecan. For the two-drug combination, there was a higher rate of moderate/severe diarrhea/myelosuppression with thalidomide 200 mg. Thus thalidomide 400 mg was combined with celecoxib. The triple combination resulted in similar toxicity as the doublet with the lower thalidomide dose. Concurrent administration of irinotecan/thalidomide did not influence pharmacokinetics. Anti-tumor responses occurred in two patients and prolonged stabilization in eight others. NF-κB activation increased over time. Patients experiencing tumor response or prolonged stabilization had lower NF-κB activation, albeit not statistically significant (P = 0.124). Conclusions: The combination of thalidomide/irinotecan is safe and devoid of PK interactions. Thalidomide 400 mg appeared more suitable for combination, whereas the addition of celecoxib did not improve tolerability. Tumor-specific studies in patients with lesser prior treatment will be necessary to establish the therapeutic impact of the combinations. Irinotecan (dpeaa)DE-He213 Celecoxib (dpeaa)DE-He213 Thalidomide (dpeaa)DE-He213 Dose Limit Toxicity (dpeaa)DE-He213 Nonhematologic Toxicity (dpeaa)DE-He213 Schaaf, Larry aut Phillips, Gary aut Otterson, Gregory aut Panico, Kevin aut Duan, Wenrui aut Kleiber, Barbara aut Shah, Manisha aut Young, Donn aut Wu, Wan-Hong aut Kuhn, John aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 59(2006), 1 vom: 10. Mai, Seite 23-33 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:59 year:2006 number:1 day:10 month:05 pages:23-33 https://dx.doi.org/10.1007/s00280-006-0249-y 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_267 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 AR 59 2006 1 10 05 23-33 |
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English |
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Enthalten in Cancer chemotherapy and pharmacology 59(2006), 1 vom: 10. Mai, Seite 23-33 volume:59 year:2006 number:1 day:10 month:05 pages:23-33 |
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Enthalten in Cancer chemotherapy and pharmacology 59(2006), 1 vom: 10. Mai, Seite 23-33 volume:59 year:2006 number:1 day:10 month:05 pages:23-33 |
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Irinotecan Celecoxib Thalidomide Dose Limit Toxicity Nonhematologic Toxicity |
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Cancer chemotherapy and pharmacology |
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Villalona-Calero, Miguel @@aut@@ Schaaf, Larry @@aut@@ Phillips, Gary @@aut@@ Otterson, Gregory @@aut@@ Panico, Kevin @@aut@@ Duan, Wenrui @@aut@@ Kleiber, Barbara @@aut@@ Shah, Manisha @@aut@@ Young, Donn @@aut@@ Wu, Wan-Hong @@aut@@ Kuhn, John @@aut@@ |
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Preclinically, thalidomide and COX-2 inhibitors reduce NF-κB activation. We tested the feasibility of combining irinotecan with thalidomide and thalidomide/celecoxib in patients with refractory malignancies. Patients/methods: The study was conducted in two parts. First, the optimal dose of thalidomide (400 or 200 mg daily) in combination with irinotecan 125 mg/$ m^{2} $ days 1 and 8 every 3 weeks was determined. In the second part, celecoxib 400 mg twice-daily was added to irinotecan/thalidomide. Pharmacokinetics of irinotecan and thalidomide alone or concurrently were evaluated. Tumor necrosis factor alpha, beta-fibroblast growth factor, and NF-κB activation were measured in blood mononuclear cells (PBMC). No CYP450 enzyme inducers/inhibitors were allowed. Results: Thirty-six patients were enrolled: Eleven received thalidomide 400 mg, 13 thalidomide 200 mg and 12 thalidomide 400 mg and celecoxib, with irinotecan. For the two-drug combination, there was a higher rate of moderate/severe diarrhea/myelosuppression with thalidomide 200 mg. Thus thalidomide 400 mg was combined with celecoxib. The triple combination resulted in similar toxicity as the doublet with the lower thalidomide dose. Concurrent administration of irinotecan/thalidomide did not influence pharmacokinetics. Anti-tumor responses occurred in two patients and prolonged stabilization in eight others. NF-κB activation increased over time. Patients experiencing tumor response or prolonged stabilization had lower NF-κB activation, albeit not statistically significant (P = 0.124). Conclusions: The combination of thalidomide/irinotecan is safe and devoid of PK interactions. Thalidomide 400 mg appeared more suitable for combination, whereas the addition of celecoxib did not improve tolerability. 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Villalona-Calero, Miguel |
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Villalona-Calero, Miguel misc Irinotecan misc Celecoxib misc Thalidomide misc Dose Limit Toxicity misc Nonhematologic Toxicity Thalidomide and celecoxib as potential modulators of irinotecan’s activity in cancer patients |
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Thalidomide and celecoxib as potential modulators of irinotecan’s activity in cancer patients Irinotecan (dpeaa)DE-He213 Celecoxib (dpeaa)DE-He213 Thalidomide (dpeaa)DE-He213 Dose Limit Toxicity (dpeaa)DE-He213 Nonhematologic Toxicity (dpeaa)DE-He213 |
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misc Irinotecan misc Celecoxib misc Thalidomide misc Dose Limit Toxicity misc Nonhematologic Toxicity |
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Thalidomide and celecoxib as potential modulators of irinotecan’s activity in cancer patients |
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Cancer chemotherapy and pharmacology |
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Villalona-Calero, Miguel Schaaf, Larry Phillips, Gary Otterson, Gregory Panico, Kevin Duan, Wenrui Kleiber, Barbara Shah, Manisha Young, Donn Wu, Wan-Hong Kuhn, John |
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Elektronische Aufsätze |
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Villalona-Calero, Miguel |
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10.1007/s00280-006-0249-y |
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thalidomide and celecoxib as potential modulators of irinotecan’s activity in cancer patients |
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Thalidomide and celecoxib as potential modulators of irinotecan’s activity in cancer patients |
| abstract |
Abstract Purpose: Nuclear factor-κB (NF-κB) activation induces resistance to irinotecan. Preclinically, thalidomide and COX-2 inhibitors reduce NF-κB activation. We tested the feasibility of combining irinotecan with thalidomide and thalidomide/celecoxib in patients with refractory malignancies. Patients/methods: The study was conducted in two parts. First, the optimal dose of thalidomide (400 or 200 mg daily) in combination with irinotecan 125 mg/$ m^{2} $ days 1 and 8 every 3 weeks was determined. In the second part, celecoxib 400 mg twice-daily was added to irinotecan/thalidomide. Pharmacokinetics of irinotecan and thalidomide alone or concurrently were evaluated. Tumor necrosis factor alpha, beta-fibroblast growth factor, and NF-κB activation were measured in blood mononuclear cells (PBMC). No CYP450 enzyme inducers/inhibitors were allowed. Results: Thirty-six patients were enrolled: Eleven received thalidomide 400 mg, 13 thalidomide 200 mg and 12 thalidomide 400 mg and celecoxib, with irinotecan. For the two-drug combination, there was a higher rate of moderate/severe diarrhea/myelosuppression with thalidomide 200 mg. Thus thalidomide 400 mg was combined with celecoxib. The triple combination resulted in similar toxicity as the doublet with the lower thalidomide dose. Concurrent administration of irinotecan/thalidomide did not influence pharmacokinetics. Anti-tumor responses occurred in two patients and prolonged stabilization in eight others. NF-κB activation increased over time. Patients experiencing tumor response or prolonged stabilization had lower NF-κB activation, albeit not statistically significant (P = 0.124). Conclusions: The combination of thalidomide/irinotecan is safe and devoid of PK interactions. Thalidomide 400 mg appeared more suitable for combination, whereas the addition of celecoxib did not improve tolerability. Tumor-specific studies in patients with lesser prior treatment will be necessary to establish the therapeutic impact of the combinations. © Springer-Verlag 2006 |
| abstractGer |
Abstract Purpose: Nuclear factor-κB (NF-κB) activation induces resistance to irinotecan. Preclinically, thalidomide and COX-2 inhibitors reduce NF-κB activation. We tested the feasibility of combining irinotecan with thalidomide and thalidomide/celecoxib in patients with refractory malignancies. Patients/methods: The study was conducted in two parts. First, the optimal dose of thalidomide (400 or 200 mg daily) in combination with irinotecan 125 mg/$ m^{2} $ days 1 and 8 every 3 weeks was determined. In the second part, celecoxib 400 mg twice-daily was added to irinotecan/thalidomide. Pharmacokinetics of irinotecan and thalidomide alone or concurrently were evaluated. Tumor necrosis factor alpha, beta-fibroblast growth factor, and NF-κB activation were measured in blood mononuclear cells (PBMC). No CYP450 enzyme inducers/inhibitors were allowed. Results: Thirty-six patients were enrolled: Eleven received thalidomide 400 mg, 13 thalidomide 200 mg and 12 thalidomide 400 mg and celecoxib, with irinotecan. For the two-drug combination, there was a higher rate of moderate/severe diarrhea/myelosuppression with thalidomide 200 mg. Thus thalidomide 400 mg was combined with celecoxib. The triple combination resulted in similar toxicity as the doublet with the lower thalidomide dose. Concurrent administration of irinotecan/thalidomide did not influence pharmacokinetics. Anti-tumor responses occurred in two patients and prolonged stabilization in eight others. NF-κB activation increased over time. Patients experiencing tumor response or prolonged stabilization had lower NF-κB activation, albeit not statistically significant (P = 0.124). Conclusions: The combination of thalidomide/irinotecan is safe and devoid of PK interactions. Thalidomide 400 mg appeared more suitable for combination, whereas the addition of celecoxib did not improve tolerability. Tumor-specific studies in patients with lesser prior treatment will be necessary to establish the therapeutic impact of the combinations. © Springer-Verlag 2006 |
| abstract_unstemmed |
Abstract Purpose: Nuclear factor-κB (NF-κB) activation induces resistance to irinotecan. Preclinically, thalidomide and COX-2 inhibitors reduce NF-κB activation. We tested the feasibility of combining irinotecan with thalidomide and thalidomide/celecoxib in patients with refractory malignancies. Patients/methods: The study was conducted in two parts. First, the optimal dose of thalidomide (400 or 200 mg daily) in combination with irinotecan 125 mg/$ m^{2} $ days 1 and 8 every 3 weeks was determined. In the second part, celecoxib 400 mg twice-daily was added to irinotecan/thalidomide. Pharmacokinetics of irinotecan and thalidomide alone or concurrently were evaluated. Tumor necrosis factor alpha, beta-fibroblast growth factor, and NF-κB activation were measured in blood mononuclear cells (PBMC). No CYP450 enzyme inducers/inhibitors were allowed. Results: Thirty-six patients were enrolled: Eleven received thalidomide 400 mg, 13 thalidomide 200 mg and 12 thalidomide 400 mg and celecoxib, with irinotecan. For the two-drug combination, there was a higher rate of moderate/severe diarrhea/myelosuppression with thalidomide 200 mg. Thus thalidomide 400 mg was combined with celecoxib. The triple combination resulted in similar toxicity as the doublet with the lower thalidomide dose. Concurrent administration of irinotecan/thalidomide did not influence pharmacokinetics. Anti-tumor responses occurred in two patients and prolonged stabilization in eight others. NF-κB activation increased over time. Patients experiencing tumor response or prolonged stabilization had lower NF-κB activation, albeit not statistically significant (P = 0.124). Conclusions: The combination of thalidomide/irinotecan is safe and devoid of PK interactions. Thalidomide 400 mg appeared more suitable for combination, whereas the addition of celecoxib did not improve tolerability. Tumor-specific studies in patients with lesser prior treatment will be necessary to establish the therapeutic impact of the combinations. © Springer-Verlag 2006 |
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| score |
7.400633 |