Skip to main content
Top
Published in: Cancer Chemotherapy and Pharmacology 4/2013

01-10-2013 | Original Article

Efficacy and safety of everolimus in Korean patients with metastatic renal cell carcinoma

Authors: Ki Hyang Kim, Sang Hyun Yoon, Hae-Jung Lee, Hyo Song Kim, Sang Joon Shin, Joong Bae Ahn, Sun Young Rha

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2013

Login to get access

Abstract

Purpose

Few studies have investigated the effects of everolimus therapy in Asian populations. This study evaluates the safety and efficacy of everolimus in Korean patients with metastatic renal cell carcinoma (mRCC).

Methods

We retrospectively reviewed records of Korean patients with mRCC (n = 22) who received everolimus between January 2009 and July 2010 and evaluated them for efficacy and safety.

Results

One patient achieved a partial response, and 16 patients had stable disease, corresponding to an overall response rate of 4.5 % and a disease control rate of 77.3 %. Median progression-free survival was 5.4 months (95 % CI 0.9–9.8). Median overall survival was not reached. Univariate analysis showed that Memorial Sloan-Kettering Cancer Center risk (P = .004), thrombocytopenia (P = .018), hyperglycemia (P = .007) and hypertriglyceridemia (P = .041) were associated with disease progression. The most common adverse events (AEs) were hypertriglyceridemia and anemia, similar to Western patients. Creatinine and aspartate aminotransferase levels were higher than those reported for Western patients. The most common grade ≥3 AEs in this study were hypertriglyceridemia and anemia, compared with lymphopenia (14 %) in Western patients.

Conclusions

Safety of everolimus in Korean mRCC patients differed from that reported in Western patients. Therefore, liver function enzymes, hemoglobin levels, lipid profile and chest CT scans should be monitored more closely in Asian mRCC patients receiving everolimus.
Literature
1.
go back to reference Stracke S, Ramudo L, Keller F, Henne-Bruns D, Mayer JM (2006) Antiproliferative and overadditive effects of everolimus and mycophenolate mofetil in pancreas and lung cancer cells in vitro. Transplant Proc 38:766–770PubMedCrossRef Stracke S, Ramudo L, Keller F, Henne-Bruns D, Mayer JM (2006) Antiproliferative and overadditive effects of everolimus and mycophenolate mofetil in pancreas and lung cancer cells in vitro. Transplant Proc 38:766–770PubMedCrossRef
2.
go back to reference Agarwala SS, Case S (2010) Everolimus (RAD001) in the treatment of advanced renal cell carcinoma: a review. Oncologist 15:236–245PubMedCrossRef Agarwala SS, Case S (2010) Everolimus (RAD001) in the treatment of advanced renal cell carcinoma: a review. Oncologist 15:236–245PubMedCrossRef
3.
go back to reference Tuncyurek P, Mayer JM, Klug F et al (2007) Everolimus and mycophenolate mofetil sensitize human pancreatic cancer cells to gemcitabine in vitro: a novel adjunct to standard chemotherapy? Eur Surg Res 39:380–387PubMedCrossRef Tuncyurek P, Mayer JM, Klug F et al (2007) Everolimus and mycophenolate mofetil sensitize human pancreatic cancer cells to gemcitabine in vitro: a novel adjunct to standard chemotherapy? Eur Surg Res 39:380–387PubMedCrossRef
4.
go back to reference Zitzmann K, De Toni EN, Brand S et al (2007) The novel mTOR inhibitor RAD001 (everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells. Neuroendocrinology 85:54–60PubMedCrossRef Zitzmann K, De Toni EN, Brand S et al (2007) The novel mTOR inhibitor RAD001 (everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells. Neuroendocrinology 85:54–60PubMedCrossRef
5.
go back to reference Calabro A, Tai J, Allen SL, Budman DR (2008) In-vitro synergism of m-TOR inhibitors, statins, and classical chemotherapy: potential implications in acute leukemia. Anticancer Drugs 19:705–712PubMedCrossRef Calabro A, Tai J, Allen SL, Budman DR (2008) In-vitro synergism of m-TOR inhibitors, statins, and classical chemotherapy: potential implications in acute leukemia. Anticancer Drugs 19:705–712PubMedCrossRef
6.
go back to reference Motzer RJ, Escudier B, Oudard S et al (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372:449–456PubMedCrossRef Motzer RJ, Escudier B, Oudard S et al (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372:449–456PubMedCrossRef
7.
go back to reference Motzer RJ, Escudier B, Oudard S et al (2010) Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 116:4256–4265PubMedCrossRef Motzer RJ, Escudier B, Oudard S et al (2010) Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 116:4256–4265PubMedCrossRef
8.
go back to reference Okamoto I, Doi T, Ohtsu A et al (2010) Phase I clinical and pharmacokinetic study of RAD001 (everolimus) administered daily to Japanese patients with advanced solid tumors. Jpn J Clin Oncol 40:17–23PubMedCrossRef Okamoto I, Doi T, Ohtsu A et al (2010) Phase I clinical and pharmacokinetic study of RAD001 (everolimus) administered daily to Japanese patients with advanced solid tumors. Jpn J Clin Oncol 40:17–23PubMedCrossRef
9.
go back to reference Tsukamoto T, Shinohara N, Tsuchiya N et al (2011) Phase III trial of everolimus in metastatic renal cell carcinoma: subgroup analysis of Japanese patients from RECORD-1. Jpn J Clin Oncol 41:17–24PubMedCrossRef Tsukamoto T, Shinohara N, Tsuchiya N et al (2011) Phase III trial of everolimus in metastatic renal cell carcinoma: subgroup analysis of Japanese patients from RECORD-1. Jpn J Clin Oncol 41:17–24PubMedCrossRef
10.
go back to reference White DA, Camus P, Endo M et al (2010) Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma. Am J Respir Crit Care Med 182:396–403PubMedCrossRef White DA, Camus P, Endo M et al (2010) Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma. Am J Respir Crit Care Med 182:396–403PubMedCrossRef
11.
go back to reference Maroto JP, Hudes G, Dutcher JP et al (2011) Drug-related pneumonitis in patients with advanced renal cell carcinoma treated with temsirolimus. J Clin Oncol 29:1750–1756PubMedCrossRef Maroto JP, Hudes G, Dutcher JP et al (2011) Drug-related pneumonitis in patients with advanced renal cell carcinoma treated with temsirolimus. J Clin Oncol 29:1750–1756PubMedCrossRef
12.
go back to reference Pham PT, Pham PC, Danovitch GM et al (2004) Sirolimus-associated pulmonary toxicity. Transplantation 77:1215–1220PubMedCrossRef Pham PT, Pham PC, Danovitch GM et al (2004) Sirolimus-associated pulmonary toxicity. Transplantation 77:1215–1220PubMedCrossRef
13.
go back to reference Chan S, Scheulen ME, Johnston S et al (2005) Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. J Clin Oncol 23:5314–5322PubMedCrossRef Chan S, Scheulen ME, Johnston S et al (2005) Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. J Clin Oncol 23:5314–5322PubMedCrossRef
14.
go back to reference Duran I, Siu LL, Oza AM et al (2006) Characterisation of the lung toxicity of the cell cycle inhibitor temsirolimus. Eur J Cancer 42:1875–1880PubMedCrossRef Duran I, Siu LL, Oza AM et al (2006) Characterisation of the lung toxicity of the cell cycle inhibitor temsirolimus. Eur J Cancer 42:1875–1880PubMedCrossRef
15.
go back to reference White DA, Schwartz LH, Dimitrijevic S, Scala LD, Hayes W, Gross SH (2009) Characterization of pneumonitis in patients with advanced non-small cell lung cancer treated with everolimus (RAD001). J Thorac Oncol 4:1357–1363PubMedCrossRef White DA, Schwartz LH, Dimitrijevic S, Scala LD, Hayes W, Gross SH (2009) Characterization of pneumonitis in patients with advanced non-small cell lung cancer treated with everolimus (RAD001). J Thorac Oncol 4:1357–1363PubMedCrossRef
16.
go back to reference Endo M, Johkoh T, Kimura K, Yamamoto N (2006) Imaging of gefitinib-related interstitial lung disease: multi-institutional analysis by the West Japan Thoracic Oncology Group. Lung Cancer 52:135–140PubMedCrossRef Endo M, Johkoh T, Kimura K, Yamamoto N (2006) Imaging of gefitinib-related interstitial lung disease: multi-institutional analysis by the West Japan Thoracic Oncology Group. Lung Cancer 52:135–140PubMedCrossRef
17.
go back to reference Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M (2002) Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 20:289–296PubMedCrossRef Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M (2002) Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 20:289–296PubMedCrossRef
18.
go back to reference Kitajima K, Takahashi S, Maeda T et al (2012) Thyroid size change by CT monitoring after sorafenib or sunitinib treatment in patients with renal cell carcinoma: comparison with thyroid function. Eur J Radiol 81:2060–2065 Kitajima K, Takahashi S, Maeda T et al (2012) Thyroid size change by CT monitoring after sorafenib or sunitinib treatment in patients with renal cell carcinoma: comparison with thyroid function. Eur J Radiol 81:2060–2065
19.
go back to reference Hudes G, Carducci M, Tomczak P et al (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271–2281PubMedCrossRef Hudes G, Carducci M, Tomczak P et al (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271–2281PubMedCrossRef
20.
go back to reference Hong MH, Kim HS, Kim C et al (2009) Treatment outcomes of sunitinib treatment in advanced renal cell carcinoma patients: a single cancer center experience in Korea. Cancer Res Treat 41:67–72PubMedCrossRef Hong MH, Kim HS, Kim C et al (2009) Treatment outcomes of sunitinib treatment in advanced renal cell carcinoma patients: a single cancer center experience in Korea. Cancer Res Treat 41:67–72PubMedCrossRef
21.
go back to reference Chollet P, Schoffski P, Weigang-Kohler K et al (2003) Phase II trial with S-1 in chemotherapy-naive patients with gastric cancer. A trial performed by the EORTC Early Clinical Studies Group (ECSG). Eur J Cancer 39:1264–1270PubMedCrossRef Chollet P, Schoffski P, Weigang-Kohler K et al (2003) Phase II trial with S-1 in chemotherapy-naive patients with gastric cancer. A trial performed by the EORTC Early Clinical Studies Group (ECSG). Eur J Cancer 39:1264–1270PubMedCrossRef
22.
go back to reference Hoff PM, Saad ED, Ajani JA et al (2003) Phase I study with pharmacokinetics of S-1 on an oral daily schedule for 28 days in patients with solid tumors. Clin Cancer Res 9:134–142PubMed Hoff PM, Saad ED, Ajani JA et al (2003) Phase I study with pharmacokinetics of S-1 on an oral daily schedule for 28 days in patients with solid tumors. Clin Cancer Res 9:134–142PubMed
Metadata
Title
Efficacy and safety of everolimus in Korean patients with metastatic renal cell carcinoma
Authors
Ki Hyang Kim
Sang Hyun Yoon
Hae-Jung Lee
Hyo Song Kim
Sang Joon Shin
Joong Bae Ahn
Sun Young Rha
Publication date
01-10-2013
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 4/2013
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-013-2266-y

Other articles of this Issue 4/2013

Cancer Chemotherapy and Pharmacology 4/2013 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine