Phase i trial of sorafenib in combination with interferon-alpha in Japanese patients with unresectable or metastatic renal cell carcinoma

Masashi Niwakawa, Katsuyoshi Hashine, Raizo Yamaguchi, Hirofumi Fujii, Yasuo Hamamoto, Koichi Fukino, Takahiko Tanigawa, Yoshiteru Sumiyoshi

研究成果: Article

12 引用 (Scopus)

抄録

Background We investigated the safety, pharmacokinetics, tumor response, and immunological parameters of sorafenib plus interferon á-2a (IFN) in Japanese patients with advanced RCC. Patients and methods After 2 weeks of IFN-alone treatment, eligible patients received 28-day cycles of continuous sorafenib 200 mg (Cohort 1) or 400 mg (Cohorts 2 and 3) twice daily combined with intramuscular IFN 6 (Cohorts 1 and 2) or 9 (Cohort 3) million international units (MIU) three times a week. Results A total of 18 patients received at least one dose of sorafenib plus IFN. Five patients had dose-limiting toxicities (DLTs). The most common DLT was fatigue, experienced in four DLT patients. All 18 patients experienced at least one treatment-emergent adverse event (AE). The most common treatment-emergent AEs included fatigue, fever, platelets, leukocytes, hemoglobin, weight loss and anorexia. Five patients had confirmed partial response and 11 had stable disease, a response rate of 27.8%. IFN had no relevant impact on the pharmacokinetics of sorafenib. Conclusions Sorafenib administered in combination with IFN was well tolerated, with promising results in efficacy. Continuous sorafenib 400 mg twice daily in combination with IFN 6 MIU three times a week is recommended in Japanese patients with advanced RCC.

元の言語English
ページ(範囲)1046-1054
ページ数9
ジャーナルInvestigational New Drugs
30
発行部数3
DOI
出版物ステータスPublished - 2012 6 1
外部発表Yes

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Renal Cell Carcinoma
Interferon-alpha
Interferons
Fatigue
Pharmacokinetics
sorafenib
Anorexia
Weight Loss
Hemoglobins
Leukocytes
Fever
Therapeutics
Blood Platelets
Safety

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

これを引用

Phase i trial of sorafenib in combination with interferon-alpha in Japanese patients with unresectable or metastatic renal cell carcinoma. / Niwakawa, Masashi; Hashine, Katsuyoshi; Yamaguchi, Raizo; Fujii, Hirofumi; Hamamoto, Yasuo; Fukino, Koichi; Tanigawa, Takahiko; Sumiyoshi, Yoshiteru.

:: Investigational New Drugs, 巻 30, 番号 3, 01.06.2012, p. 1046-1054.

研究成果: Article

Niwakawa, Masashi ; Hashine, Katsuyoshi ; Yamaguchi, Raizo ; Fujii, Hirofumi ; Hamamoto, Yasuo ; Fukino, Koichi ; Tanigawa, Takahiko ; Sumiyoshi, Yoshiteru. / Phase i trial of sorafenib in combination with interferon-alpha in Japanese patients with unresectable or metastatic renal cell carcinoma. :: Investigational New Drugs. 2012 ; 巻 30, 番号 3. pp. 1046-1054.
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abstract = "Background We investigated the safety, pharmacokinetics, tumor response, and immunological parameters of sorafenib plus interferon {\'a}-2a (IFN) in Japanese patients with advanced RCC. Patients and methods After 2 weeks of IFN-alone treatment, eligible patients received 28-day cycles of continuous sorafenib 200 mg (Cohort 1) or 400 mg (Cohorts 2 and 3) twice daily combined with intramuscular IFN 6 (Cohorts 1 and 2) or 9 (Cohort 3) million international units (MIU) three times a week. Results A total of 18 patients received at least one dose of sorafenib plus IFN. Five patients had dose-limiting toxicities (DLTs). The most common DLT was fatigue, experienced in four DLT patients. All 18 patients experienced at least one treatment-emergent adverse event (AE). The most common treatment-emergent AEs included fatigue, fever, platelets, leukocytes, hemoglobin, weight loss and anorexia. Five patients had confirmed partial response and 11 had stable disease, a response rate of 27.8{\%}. IFN had no relevant impact on the pharmacokinetics of sorafenib. Conclusions Sorafenib administered in combination with IFN was well tolerated, with promising results in efficacy. Continuous sorafenib 400 mg twice daily in combination with IFN 6 MIU three times a week is recommended in Japanese patients with advanced RCC.",
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AU - Niwakawa, Masashi

AU - Hashine, Katsuyoshi

AU - Yamaguchi, Raizo

AU - Fujii, Hirofumi

AU - Hamamoto, Yasuo

AU - Fukino, Koichi

AU - Tanigawa, Takahiko

AU - Sumiyoshi, Yoshiteru

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N2 - Background We investigated the safety, pharmacokinetics, tumor response, and immunological parameters of sorafenib plus interferon á-2a (IFN) in Japanese patients with advanced RCC. Patients and methods After 2 weeks of IFN-alone treatment, eligible patients received 28-day cycles of continuous sorafenib 200 mg (Cohort 1) or 400 mg (Cohorts 2 and 3) twice daily combined with intramuscular IFN 6 (Cohorts 1 and 2) or 9 (Cohort 3) million international units (MIU) three times a week. Results A total of 18 patients received at least one dose of sorafenib plus IFN. Five patients had dose-limiting toxicities (DLTs). The most common DLT was fatigue, experienced in four DLT patients. All 18 patients experienced at least one treatment-emergent adverse event (AE). The most common treatment-emergent AEs included fatigue, fever, platelets, leukocytes, hemoglobin, weight loss and anorexia. Five patients had confirmed partial response and 11 had stable disease, a response rate of 27.8%. IFN had no relevant impact on the pharmacokinetics of sorafenib. Conclusions Sorafenib administered in combination with IFN was well tolerated, with promising results in efficacy. Continuous sorafenib 400 mg twice daily in combination with IFN 6 MIU three times a week is recommended in Japanese patients with advanced RCC.

AB - Background We investigated the safety, pharmacokinetics, tumor response, and immunological parameters of sorafenib plus interferon á-2a (IFN) in Japanese patients with advanced RCC. Patients and methods After 2 weeks of IFN-alone treatment, eligible patients received 28-day cycles of continuous sorafenib 200 mg (Cohort 1) or 400 mg (Cohorts 2 and 3) twice daily combined with intramuscular IFN 6 (Cohorts 1 and 2) or 9 (Cohort 3) million international units (MIU) three times a week. Results A total of 18 patients received at least one dose of sorafenib plus IFN. Five patients had dose-limiting toxicities (DLTs). The most common DLT was fatigue, experienced in four DLT patients. All 18 patients experienced at least one treatment-emergent adverse event (AE). The most common treatment-emergent AEs included fatigue, fever, platelets, leukocytes, hemoglobin, weight loss and anorexia. Five patients had confirmed partial response and 11 had stable disease, a response rate of 27.8%. IFN had no relevant impact on the pharmacokinetics of sorafenib. Conclusions Sorafenib administered in combination with IFN was well tolerated, with promising results in efficacy. Continuous sorafenib 400 mg twice daily in combination with IFN 6 MIU three times a week is recommended in Japanese patients with advanced RCC.

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