TY - JOUR
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
N1 - Funding Information:
Dr Mizuno reports receiving grants from The Japan Agency for Medical Research and Development (AMED), personal fees from Pfizer, and grants and personal fees from Novartis during the conduct of the study; Dr Mikami reports receiving grants from The Japan Agency for Medical Research and Development (AMED) during the conduct of the study; Dr Oya reports receiving grants from The Japan Agency for Medical Research and Development (AMED), grants and personal fees from Pfizer, grants and personal fees from Novartis, and personal fees from Bayer during the conduct of the study. All other authors state that they have no conflicts of interest.
Funding Information:
The authors would like to thank all members of the Keio Collaboration Study of Renal Cell Carcinoma. The following institutions participated in this study: Keio University School of Medicine, Tokyo, Japan; Saitama Medical University International Medical Center, Hidaka, Saitama, Japan; National Defense Medical College, Tokorozawa, Saitama, Japan; Saiseikai Central Hospital, Tokyo, Japan; Saitama City Hospital, Saitama, Japan; National Hospital Organization Saitama Hospital, Wako, Saitama, Japan; and Ichikawa General Hospital, Tokyo Dental College, Ichikawa, Chiba, Japan. This work was supported in part by Grants-in-Aid for Scientific Research (#26462429 to N. Tanaka and #15H04977 to M. Oya) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (#26462429 to N. Tanaka and #15H04977 to M. Oya). This study was performed as a research program of the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct), Ministry of Education, Culture, Sports, Science, and Technology of Japan.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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.
AB - 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.
KW - Dose modification
KW - IMDC
KW - Outcome
KW - RDI
KW - Renal cell carcinoma
KW - Second-line
KW - Targeted therapy
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U2 - 10.1016/j.clgc.2016.03.014
DO - 10.1016/j.clgc.2016.03.014
M3 - Article
C2 - 27102405
AN - SCOPUS:84963527495
SN - 1558-7673
VL - 14
SP - e575-e583
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 6
ER -