Abstract
Recent reports showed that thalidomide has anti-angiogenic activity and is effective for the treatment of refractory multiple myeloma (MM). We examined the relationship between the clinical efficacy and adverse effects of thalidomide and the plasma concentrations of this drug as well as angiogenic growth factors in refractory MM. Ten out of twenty-four evaluable patients (42%) showed more than 25% reduction of M-protein, and eight (33%) achieved more than 50% reduction. These changes were associated with restoration of anemia and recovery of normal immunoglobulin level. Somnolence and headache, constipation, peripheral neuropathy and skin rash were frequently observed, but were well tolerated. However, grade 2-4 severe neutropenia was also observed in nine cases. These adverse effects other than neutropenia occurred more frequently in the patients with higher plasma concentrations of thalidomide (≥2.0 μg/ml at 12 h after the last administration) and were readily alleviated by dose reduction. In contrast, neutropenia developed regardless of the plasma concentration. Plasma concentrations of angiogenic growth factors were frequently elevated before treatment. After thalidomide treatment, these growth factor levels tend to decrease to near-normal ranges in responders but were still high in most non-responders. After thalidomide treatment, plasma vascular endothelial growth factor (VEGF) level was significantly reduced in responders (P=0.025), but not in non-responders (P=0.37). Reduction of plasma VEGF level might be an important indicator for anti-myeloma effect of thalidomide.
| Original language | English |
|---|---|
| Pages (from-to) | 1029-1036 |
| Number of pages | 8 |
| Journal | Japanese Journal of Cancer Research |
| Volume | 93 |
| Issue number | 9 |
| Publication status | Published - 2002 Sep 1 |
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Keywords
- Fibroblast growth factor
- Multiple myeloma
- Neutropenia
- Thalidomide
- Vascular endothelial growth factor
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Thalidomide for the treatment of refractory multiple myeloma : Association of plasma concentrations of thalidomide and angiogenic growth factors with clinical outcome. / Kakimoto, Tsunayaki; Hattori, Yutaka; Okamoto, Shinichiro; Sato, Norihide; Kamata, Tamihiro; Yamaguchi, Masaya; Morita, Kunihiko; Yamada, Taketo; Takayama, Nobuyuki; Uchida, Hideo; Shimada, Naoki; Tanigawara, Yusuke; Ikeda, Yasuo.
In: Japanese Journal of Cancer Research, Vol. 93, No. 9, 01.09.2002, p. 1029-1036.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Thalidomide for the treatment of refractory multiple myeloma
T2 - Association of plasma concentrations of thalidomide and angiogenic growth factors with clinical outcome
AU - Kakimoto, Tsunayaki
AU - Hattori, Yutaka
AU - Okamoto, Shinichiro
AU - Sato, Norihide
AU - Kamata, Tamihiro
AU - Yamaguchi, Masaya
AU - Morita, Kunihiko
AU - Yamada, Taketo
AU - Takayama, Nobuyuki
AU - Uchida, Hideo
AU - Shimada, Naoki
AU - Tanigawara, Yusuke
AU - Ikeda, Yasuo
PY - 2002/9/1
Y1 - 2002/9/1
N2 - Recent reports showed that thalidomide has anti-angiogenic activity and is effective for the treatment of refractory multiple myeloma (MM). We examined the relationship between the clinical efficacy and adverse effects of thalidomide and the plasma concentrations of this drug as well as angiogenic growth factors in refractory MM. Ten out of twenty-four evaluable patients (42%) showed more than 25% reduction of M-protein, and eight (33%) achieved more than 50% reduction. These changes were associated with restoration of anemia and recovery of normal immunoglobulin level. Somnolence and headache, constipation, peripheral neuropathy and skin rash were frequently observed, but were well tolerated. However, grade 2-4 severe neutropenia was also observed in nine cases. These adverse effects other than neutropenia occurred more frequently in the patients with higher plasma concentrations of thalidomide (≥2.0 μg/ml at 12 h after the last administration) and were readily alleviated by dose reduction. In contrast, neutropenia developed regardless of the plasma concentration. Plasma concentrations of angiogenic growth factors were frequently elevated before treatment. After thalidomide treatment, these growth factor levels tend to decrease to near-normal ranges in responders but were still high in most non-responders. After thalidomide treatment, plasma vascular endothelial growth factor (VEGF) level was significantly reduced in responders (P=0.025), but not in non-responders (P=0.37). Reduction of plasma VEGF level might be an important indicator for anti-myeloma effect of thalidomide.
AB - Recent reports showed that thalidomide has anti-angiogenic activity and is effective for the treatment of refractory multiple myeloma (MM). We examined the relationship between the clinical efficacy and adverse effects of thalidomide and the plasma concentrations of this drug as well as angiogenic growth factors in refractory MM. Ten out of twenty-four evaluable patients (42%) showed more than 25% reduction of M-protein, and eight (33%) achieved more than 50% reduction. These changes were associated with restoration of anemia and recovery of normal immunoglobulin level. Somnolence and headache, constipation, peripheral neuropathy and skin rash were frequently observed, but were well tolerated. However, grade 2-4 severe neutropenia was also observed in nine cases. These adverse effects other than neutropenia occurred more frequently in the patients with higher plasma concentrations of thalidomide (≥2.0 μg/ml at 12 h after the last administration) and were readily alleviated by dose reduction. In contrast, neutropenia developed regardless of the plasma concentration. Plasma concentrations of angiogenic growth factors were frequently elevated before treatment. After thalidomide treatment, these growth factor levels tend to decrease to near-normal ranges in responders but were still high in most non-responders. After thalidomide treatment, plasma vascular endothelial growth factor (VEGF) level was significantly reduced in responders (P=0.025), but not in non-responders (P=0.37). Reduction of plasma VEGF level might be an important indicator for anti-myeloma effect of thalidomide.
KW - Fibroblast growth factor
KW - Multiple myeloma
KW - Neutropenia
KW - Thalidomide
KW - Vascular endothelial growth factor
UR - http://www.scopus.com/inward/record.url?scp=0036748453&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036748453&partnerID=8YFLogxK
M3 - Article
C2 - 12359057
AN - SCOPUS:0036748453
VL - 93
SP - 1029
EP - 1036
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 9
ER -