Phase II study of the safety and efficacy of temsirolimus in east asian patients with advanced renal cell carcinoma

Yan Sun, Sun Rha, Se Hoon Lee, Jun Guo, Takeshi Ueda, Shukui Qin, Seiji Naito, Maria Cincotta, Kota Tokushige, Hideyuki Akaza

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Objective: Temsirolimus, an inhibitor of the mammalian target of rapamycin, is approved for treatment of patients with advanced renal cell carcinoma in the USA and Europe. Temsirolimus was not yet evaluated in East Asian patients. Methods: This non-randomized Phase II study enrolled 82 patients with advanced renal cell carcinoma [20 (24%) Japanese, 30 (37%) Korean and 32 (39%) Chinese patients; median age (range): 55 (26-83) years]. Most (71%) received prior systemic therapy for metastatic disease; two-thirds were intermediate risk. Six Japanese patients received intravenous temsirolimus 20 mg/m. 2 weekly for tolerability assessment (Group A); the remaining 76 received a 25 mg flat dose weekly (Group B). Temsirolimus was dosed once weekly. Primary efficacy end point was the Response Evaluation Criteria in Solid Tumors-defined clinical benefit rate in the intent-to-treat population. Results: In the entire population, regardless of treatment group, the clinical benefit rate was 48% (95% confidence interval: 36, 59). Objective response rate was 11% (95% confidence interval: 5, 20), median progression-free survival was 7.3 months (95% confidence interval: 4.0, 9.2) and median time to treatment failure was 5.4 months (95% confidence interval: 3.5, 7.4). No patient in Group A demonstrated dose-limiting toxicity. The most frequent Grade 3 or 4 drug-related adverse events were anemia, hyperglycemia, hypophosphatemia and stomatitis (5% each). Serious adverse events reported in ≥5% of patients were pneumonia (9%) and interstitial lung disease (7%). Temsirolimus and its major metabolite, sirolimus, were long-lived throughout the dosage interval, with no evidence of accumulation. Conclusion: Temsirolimus was well tolerated and showed promising activity in Japanese, Korean and Chinese patients with advanced renal cell carcinoma.

Original languageEnglish
Article numberhys110
Pages (from-to)836-844
Number of pages9
JournalJapanese Journal of Clinical Oncology
Volume42
Issue number9
DOIs
Publication statusPublished - 2012 Sep 1

Fingerprint

Renal Cell Carcinoma
Safety
Confidence Intervals
Sirolimus
Hypophosphatemia
Stomatitis
temsirolimus
Interstitial Lung Diseases
Drug-Related Side Effects and Adverse Reactions
Treatment Failure
Hyperglycemia
Population
Disease-Free Survival
Anemia
Pneumonia
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Sun, Yan ; Rha, Sun ; Lee, Se Hoon ; Guo, Jun ; Ueda, Takeshi ; Qin, Shukui ; Naito, Seiji ; Cincotta, Maria ; Tokushige, Kota ; Akaza, Hideyuki. / Phase II study of the safety and efficacy of temsirolimus in east asian patients with advanced renal cell carcinoma. In: Japanese Journal of Clinical Oncology. 2012 ; Vol. 42, No. 9. pp. 836-844.
@article{d3ecb2a484884bc9a76b7c4dee4b70b3,
title = "Phase II study of the safety and efficacy of temsirolimus in east asian patients with advanced renal cell carcinoma",
abstract = "Objective: Temsirolimus, an inhibitor of the mammalian target of rapamycin, is approved for treatment of patients with advanced renal cell carcinoma in the USA and Europe. Temsirolimus was not yet evaluated in East Asian patients. Methods: This non-randomized Phase II study enrolled 82 patients with advanced renal cell carcinoma [20 (24{\%}) Japanese, 30 (37{\%}) Korean and 32 (39{\%}) Chinese patients; median age (range): 55 (26-83) years]. Most (71{\%}) received prior systemic therapy for metastatic disease; two-thirds were intermediate risk. Six Japanese patients received intravenous temsirolimus 20 mg/m. 2 weekly for tolerability assessment (Group A); the remaining 76 received a 25 mg flat dose weekly (Group B). Temsirolimus was dosed once weekly. Primary efficacy end point was the Response Evaluation Criteria in Solid Tumors-defined clinical benefit rate in the intent-to-treat population. Results: In the entire population, regardless of treatment group, the clinical benefit rate was 48{\%} (95{\%} confidence interval: 36, 59). Objective response rate was 11{\%} (95{\%} confidence interval: 5, 20), median progression-free survival was 7.3 months (95{\%} confidence interval: 4.0, 9.2) and median time to treatment failure was 5.4 months (95{\%} confidence interval: 3.5, 7.4). No patient in Group A demonstrated dose-limiting toxicity. The most frequent Grade 3 or 4 drug-related adverse events were anemia, hyperglycemia, hypophosphatemia and stomatitis (5{\%} each). Serious adverse events reported in ≥5{\%} of patients were pneumonia (9{\%}) and interstitial lung disease (7{\%}). Temsirolimus and its major metabolite, sirolimus, were long-lived throughout the dosage interval, with no evidence of accumulation. Conclusion: Temsirolimus was well tolerated and showed promising activity in Japanese, Korean and Chinese patients with advanced renal cell carcinoma.",
author = "Yan Sun and Sun Rha and Lee, {Se Hoon} and Jun Guo and Takeshi Ueda and Shukui Qin and Seiji Naito and Maria Cincotta and Kota Tokushige and Hideyuki Akaza",
year = "2012",
month = "9",
day = "1",
doi = "10.1093/jjco/hys110",
language = "English",
volume = "42",
pages = "836--844",
journal = "Japanese Journal of Clinical Oncology",
issn = "0368-2811",
publisher = "Oxford University Press",
number = "9",

}

Sun, Y, Rha, S, Lee, SH, Guo, J, Ueda, T, Qin, S, Naito, S, Cincotta, M, Tokushige, K & Akaza, H 2012, 'Phase II study of the safety and efficacy of temsirolimus in east asian patients with advanced renal cell carcinoma', Japanese Journal of Clinical Oncology, vol. 42, no. 9, hys110, pp. 836-844. https://doi.org/10.1093/jjco/hys110

Phase II study of the safety and efficacy of temsirolimus in east asian patients with advanced renal cell carcinoma. / Sun, Yan; Rha, Sun; Lee, Se Hoon; Guo, Jun; Ueda, Takeshi; Qin, Shukui; Naito, Seiji; Cincotta, Maria; Tokushige, Kota; Akaza, Hideyuki.

In: Japanese Journal of Clinical Oncology, Vol. 42, No. 9, hys110, 01.09.2012, p. 836-844.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase II study of the safety and efficacy of temsirolimus in east asian patients with advanced renal cell carcinoma

AU - Sun, Yan

AU - Rha, Sun

AU - Lee, Se Hoon

AU - Guo, Jun

AU - Ueda, Takeshi

AU - Qin, Shukui

AU - Naito, Seiji

AU - Cincotta, Maria

AU - Tokushige, Kota

AU - Akaza, Hideyuki

PY - 2012/9/1

Y1 - 2012/9/1

N2 - Objective: Temsirolimus, an inhibitor of the mammalian target of rapamycin, is approved for treatment of patients with advanced renal cell carcinoma in the USA and Europe. Temsirolimus was not yet evaluated in East Asian patients. Methods: This non-randomized Phase II study enrolled 82 patients with advanced renal cell carcinoma [20 (24%) Japanese, 30 (37%) Korean and 32 (39%) Chinese patients; median age (range): 55 (26-83) years]. Most (71%) received prior systemic therapy for metastatic disease; two-thirds were intermediate risk. Six Japanese patients received intravenous temsirolimus 20 mg/m. 2 weekly for tolerability assessment (Group A); the remaining 76 received a 25 mg flat dose weekly (Group B). Temsirolimus was dosed once weekly. Primary efficacy end point was the Response Evaluation Criteria in Solid Tumors-defined clinical benefit rate in the intent-to-treat population. Results: In the entire population, regardless of treatment group, the clinical benefit rate was 48% (95% confidence interval: 36, 59). Objective response rate was 11% (95% confidence interval: 5, 20), median progression-free survival was 7.3 months (95% confidence interval: 4.0, 9.2) and median time to treatment failure was 5.4 months (95% confidence interval: 3.5, 7.4). No patient in Group A demonstrated dose-limiting toxicity. The most frequent Grade 3 or 4 drug-related adverse events were anemia, hyperglycemia, hypophosphatemia and stomatitis (5% each). Serious adverse events reported in ≥5% of patients were pneumonia (9%) and interstitial lung disease (7%). Temsirolimus and its major metabolite, sirolimus, were long-lived throughout the dosage interval, with no evidence of accumulation. Conclusion: Temsirolimus was well tolerated and showed promising activity in Japanese, Korean and Chinese patients with advanced renal cell carcinoma.

AB - Objective: Temsirolimus, an inhibitor of the mammalian target of rapamycin, is approved for treatment of patients with advanced renal cell carcinoma in the USA and Europe. Temsirolimus was not yet evaluated in East Asian patients. Methods: This non-randomized Phase II study enrolled 82 patients with advanced renal cell carcinoma [20 (24%) Japanese, 30 (37%) Korean and 32 (39%) Chinese patients; median age (range): 55 (26-83) years]. Most (71%) received prior systemic therapy for metastatic disease; two-thirds were intermediate risk. Six Japanese patients received intravenous temsirolimus 20 mg/m. 2 weekly for tolerability assessment (Group A); the remaining 76 received a 25 mg flat dose weekly (Group B). Temsirolimus was dosed once weekly. Primary efficacy end point was the Response Evaluation Criteria in Solid Tumors-defined clinical benefit rate in the intent-to-treat population. Results: In the entire population, regardless of treatment group, the clinical benefit rate was 48% (95% confidence interval: 36, 59). Objective response rate was 11% (95% confidence interval: 5, 20), median progression-free survival was 7.3 months (95% confidence interval: 4.0, 9.2) and median time to treatment failure was 5.4 months (95% confidence interval: 3.5, 7.4). No patient in Group A demonstrated dose-limiting toxicity. The most frequent Grade 3 or 4 drug-related adverse events were anemia, hyperglycemia, hypophosphatemia and stomatitis (5% each). Serious adverse events reported in ≥5% of patients were pneumonia (9%) and interstitial lung disease (7%). Temsirolimus and its major metabolite, sirolimus, were long-lived throughout the dosage interval, with no evidence of accumulation. Conclusion: Temsirolimus was well tolerated and showed promising activity in Japanese, Korean and Chinese patients with advanced renal cell carcinoma.

UR - http://www.scopus.com/inward/record.url?scp=84865573404&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865573404&partnerID=8YFLogxK

U2 - 10.1093/jjco/hys110

DO - 10.1093/jjco/hys110

M3 - Article

C2 - 22844126

AN - SCOPUS:84865573404

VL - 42

SP - 836

EP - 844

JO - Japanese Journal of Clinical Oncology

JF - Japanese Journal of Clinical Oncology

SN - 0368-2811

IS - 9

M1 - hys110

ER -