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

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5 Citations (Scopus)

Abstract

The relative dose intensity (RDI) at 4 weeks after second-line targeted therapy induction may be a possible predictor of prognosis in patients with metastatic renal cell carcinoma treated with second-line targeted therapy, particularly in the International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group and everolimus-treated subjects. Overall survival of patients with second-line RDI < 0.7 is significantly shorter than those with RDI ≥ 0.7. 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
Pages (from-to)e575-e583
JournalClinical Genitourinary Cancer
Volume14
Issue number6
DOIs
Publication statusPublished - 2016 Dec 1

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Urology

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  • Cite this

    Shirotake, S., Yasumizu, Y., Ito, K., Masunaga, A., Ito, Y., Miyazaki, Y., Hagiwara, M., Kanao, K., Mikami, S., Nakagawa, K., Momma, T., Masuda, T., Asano, T., Oyama, M., Tanaka, N., Mizuno, R., & Oya, M. (2016). Impact of Second-Line Targeted Therapy Dose Intensity on Patients With Metastatic Renal Cell Carcinoma. Clinical Genitourinary Cancer, 14(6), e575-e583. https://doi.org/10.1016/j.clgc.2016.03.014