Impact of Second-Line Targeted Therapy Dose Intensity on Patients With Metastatic Renal Cell Carcinoma

Suguru Shirotake, Yota Yasumizu, Keiichi Ito, Ayako Masunaga, Yujiro Ito, Yasumasa Miyazaki, Masayuki Hagiwara, Kent Kanao, Shuji Mikami, Ken Nakagawa, Tetsuo Momma, Takeshi Masuda, Tomohiko Asano, Masafumi Oyama, Nobuyuki Tanaka, Ryuichi Mizuno, Mototsugu Oya

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Relative dose intensity (RDI) is a simple index for evaluation of the amount of drug administered per unit time. We retrospectively investigated the prognostic impact of RDI for patients with metastatic renal cell carcinoma (mRCC) treated with second-line targeted therapy. Methods: We enrolled 168 patients with mRCC. We assessed RDI at 4 weeks after second-line targeted therapy induction. Results: The median follow-up after second-line targeted therapy was 18.1 months. The median time-to-treatment-failure (TTF) and overall survival (OS) were 4.9 and 25.4 months, respectively. In the Kaplan-Meier analysis, the median OS of patients with second-line RDI <0.7 was significantly shorter than those with RDI ≥ 0.7 (12.1 vs. 31.3 months; P = .030). In the subgroup analysis, second-line RDI was definitely prognostic in the poor-risk group of the International Metastatic Renal Cell Carcinoma Database Consortium criteria, showing second-line RDI was an independent predictor for both TTF (hazard ratio [HR], 3.6; 95% confidence interval [CI], 1.6-8.0; P = .002) and OS (HR, 3.1; 95% CI, 1.1-8.4; P = .026). Also, assessing the type of second-line regimen, the multivariate analysis showed that second-line RDI was an independent prognostic indicator of TTF (HR, 1.7; 95% CI, 1.0-2.9; P = .040) and OS (HR, 2.7; 95% CI, 1.3-5.7; P = .009) in patients treated with everolimus. In this group, the median TTF and OS of patients with RDI <0.7 were 2.4 and 11.1 months, and those with RDI ≥ 0.7 were 5.3 and 25.9 months, respectively. Conclusion: The results suggest that second-line RDI may be a prognostic predictor for patients with mRCC treated with second-line targeted therapy, particularly in both the International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group and everolimus-treated group.

Original languageEnglish
JournalClinical Genitourinary Cancer
DOIs
Publication statusAccepted/In press - 2016 Jan 30

Fingerprint

Renal Cell Carcinoma
Treatment Failure
Survival
Confidence Intervals
Therapeutics
Databases
Drug Evaluation
Kaplan-Meier Estimate
Multivariate Analysis

Keywords

  • Dose modification
  • IMDC
  • Outcome
  • RDI
  • Renal cell carcinoma
  • Second-line
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Impact of Second-Line Targeted Therapy Dose Intensity on Patients With Metastatic Renal Cell Carcinoma. / Shirotake, Suguru; Yasumizu, Yota; Ito, Keiichi; Masunaga, Ayako; Ito, Yujiro; Miyazaki, Yasumasa; Hagiwara, Masayuki; Kanao, Kent; Mikami, Shuji; Nakagawa, Ken; Momma, Tetsuo; Masuda, Takeshi; Asano, Tomohiko; Oyama, Masafumi; Tanaka, Nobuyuki; Mizuno, Ryuichi; Oya, Mototsugu.

In: Clinical Genitourinary Cancer, 30.01.2016.

Research output: Contribution to journalArticle

Shirotake, Suguru ; Yasumizu, Yota ; Ito, Keiichi ; Masunaga, Ayako ; Ito, Yujiro ; Miyazaki, Yasumasa ; Hagiwara, Masayuki ; Kanao, Kent ; Mikami, Shuji ; Nakagawa, Ken ; Momma, Tetsuo ; Masuda, Takeshi ; Asano, Tomohiko ; Oyama, Masafumi ; Tanaka, Nobuyuki ; Mizuno, Ryuichi ; Oya, Mototsugu. / Impact of Second-Line Targeted Therapy Dose Intensity on Patients With Metastatic Renal Cell Carcinoma. In: Clinical Genitourinary Cancer. 2016.
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abstract = "Background: Relative dose intensity (RDI) is a simple index for evaluation of the amount of drug administered per unit time. We retrospectively investigated the prognostic impact of RDI for patients with metastatic renal cell carcinoma (mRCC) treated with second-line targeted therapy. Methods: We enrolled 168 patients with mRCC. We assessed RDI at 4 weeks after second-line targeted therapy induction. Results: The median follow-up after second-line targeted therapy was 18.1 months. The median time-to-treatment-failure (TTF) and overall survival (OS) were 4.9 and 25.4 months, respectively. In the Kaplan-Meier analysis, the median OS of patients with second-line RDI <0.7 was significantly shorter than those with RDI ≥ 0.7 (12.1 vs. 31.3 months; P = .030). In the subgroup analysis, second-line RDI was definitely prognostic in the poor-risk group of the International Metastatic Renal Cell Carcinoma Database Consortium criteria, showing second-line RDI was an independent predictor for both TTF (hazard ratio [HR], 3.6; 95{\%} confidence interval [CI], 1.6-8.0; P = .002) and OS (HR, 3.1; 95{\%} CI, 1.1-8.4; P = .026). Also, assessing the type of second-line regimen, the multivariate analysis showed that second-line RDI was an independent prognostic indicator of TTF (HR, 1.7; 95{\%} CI, 1.0-2.9; P = .040) and OS (HR, 2.7; 95{\%} CI, 1.3-5.7; P = .009) in patients treated with everolimus. In this group, the median TTF and OS of patients with RDI <0.7 were 2.4 and 11.1 months, and those with RDI ≥ 0.7 were 5.3 and 25.9 months, respectively. Conclusion: The results suggest that second-line RDI may be a prognostic predictor for patients with mRCC treated with second-line targeted therapy, particularly in both the International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group and everolimus-treated group.",
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T1 - Impact of Second-Line Targeted Therapy Dose Intensity on Patients With Metastatic Renal Cell Carcinoma

AU - Shirotake, Suguru

AU - Yasumizu, Yota

AU - Ito, Keiichi

AU - Masunaga, Ayako

AU - Ito, Yujiro

AU - Miyazaki, Yasumasa

AU - Hagiwara, Masayuki

AU - Kanao, Kent

AU - Mikami, Shuji

AU - Nakagawa, Ken

AU - Momma, Tetsuo

AU - Masuda, Takeshi

AU - Asano, Tomohiko

AU - Oyama, Masafumi

AU - Tanaka, Nobuyuki

AU - Mizuno, Ryuichi

AU - Oya, Mototsugu

PY - 2016/1/30

Y1 - 2016/1/30

N2 - Background: Relative dose intensity (RDI) is a simple index for evaluation of the amount of drug administered per unit time. We retrospectively investigated the prognostic impact of RDI for patients with metastatic renal cell carcinoma (mRCC) treated with second-line targeted therapy. Methods: We enrolled 168 patients with mRCC. We assessed RDI at 4 weeks after second-line targeted therapy induction. Results: The median follow-up after second-line targeted therapy was 18.1 months. The median time-to-treatment-failure (TTF) and overall survival (OS) were 4.9 and 25.4 months, respectively. In the Kaplan-Meier analysis, the median OS of patients with second-line RDI <0.7 was significantly shorter than those with RDI ≥ 0.7 (12.1 vs. 31.3 months; P = .030). In the subgroup analysis, second-line RDI was definitely prognostic in the poor-risk group of the International Metastatic Renal Cell Carcinoma Database Consortium criteria, showing second-line RDI was an independent predictor for both TTF (hazard ratio [HR], 3.6; 95% confidence interval [CI], 1.6-8.0; P = .002) and OS (HR, 3.1; 95% CI, 1.1-8.4; P = .026). Also, assessing the type of second-line regimen, the multivariate analysis showed that second-line RDI was an independent prognostic indicator of TTF (HR, 1.7; 95% CI, 1.0-2.9; P = .040) and OS (HR, 2.7; 95% CI, 1.3-5.7; P = .009) in patients treated with everolimus. In this group, the median TTF and OS of patients with RDI <0.7 were 2.4 and 11.1 months, and those with RDI ≥ 0.7 were 5.3 and 25.9 months, respectively. Conclusion: The results suggest that second-line RDI may be a prognostic predictor for patients with mRCC treated with second-line targeted therapy, particularly in both the International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group and everolimus-treated group.

AB - Background: Relative dose intensity (RDI) is a simple index for evaluation of the amount of drug administered per unit time. We retrospectively investigated the prognostic impact of RDI for patients with metastatic renal cell carcinoma (mRCC) treated with second-line targeted therapy. Methods: We enrolled 168 patients with mRCC. We assessed RDI at 4 weeks after second-line targeted therapy induction. Results: The median follow-up after second-line targeted therapy was 18.1 months. The median time-to-treatment-failure (TTF) and overall survival (OS) were 4.9 and 25.4 months, respectively. In the Kaplan-Meier analysis, the median OS of patients with second-line RDI <0.7 was significantly shorter than those with RDI ≥ 0.7 (12.1 vs. 31.3 months; P = .030). In the subgroup analysis, second-line RDI was definitely prognostic in the poor-risk group of the International Metastatic Renal Cell Carcinoma Database Consortium criteria, showing second-line RDI was an independent predictor for both TTF (hazard ratio [HR], 3.6; 95% confidence interval [CI], 1.6-8.0; P = .002) and OS (HR, 3.1; 95% CI, 1.1-8.4; P = .026). Also, assessing the type of second-line regimen, the multivariate analysis showed that second-line RDI was an independent prognostic indicator of TTF (HR, 1.7; 95% CI, 1.0-2.9; P = .040) and OS (HR, 2.7; 95% CI, 1.3-5.7; P = .009) in patients treated with everolimus. In this group, the median TTF and OS of patients with RDI <0.7 were 2.4 and 11.1 months, and those with RDI ≥ 0.7 were 5.3 and 25.9 months, respectively. Conclusion: The results suggest that second-line RDI may be a prognostic predictor for patients with mRCC treated with second-line targeted therapy, particularly in both the International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group and everolimus-treated group.

KW - Dose modification

KW - IMDC

KW - Outcome

KW - RDI

KW - Renal cell carcinoma

KW - Second-line

KW - Targeted therapy

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