Frequent Dose Interruptions are Required for Patients Receiving Oral Kinase Inhibitor Therapy for Advanced Renal Cell Carcinoma

被引:32
作者
La Vine, David B. T. [1 ]
Coleman, Teresa A.
Davis, Carol H.
Carbonell, Christine E.
Davis, Wendy B.
机构
[1] Med Coll Georgia, Dept Med, Sect Hematol & Oncol, Sch Med, Augusta, GA 30912 USA
来源
AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS | 2010年 / 33卷 / 03期
关键词
renal cell carcinoma; reverse tyrosine kinase inhibitors; sorafenib; sunitinib; toxicities; RAF KINASE; PHARMACOKINETICS; SORAFENIB; SUNITINIB; CANCER; SAFETY;
D O I
10.1097/COC.0b013e3181a650a6
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objective: Recent advances for patients with advanced or metastatic renal cell carcinoma (RCC) have been shown to improve progression-free survival with both response rates and disease stabilizing activity. Sorafenib, a multikinase inhibitor, and sunitinib, an inhibitor of vascular endothelial growth factor-r and platelet-derived growth factor-r, have been approved by the Food and Drug Administration since 2005/2006. This retrospective analysis of patients treated with both aforementioned kinase inhibitors for advanced RCC presents data related to their antitumor effects as well as safety profile with particular attention to dose interruption and modification requirements. Methods: This was a retrospective review of patients diagnosed with RCC either with advanced disease at initial presentation or after first-line therapy, who received either continuous sorafenib 400 mg bid or sunitinib 50 mg Qday for 4 weeks on and 2 weeks off until disease progression or untoward drug reaction. Tumor response was evaluated by response evaluation criteria in solid tumors criteria, and adverse events were graded by National Cancer Institute-Common Toxicity Criteria. Results: From December 2005 to May 2008, 34 patients were followed. Twenty-two patients received sorafenib first line, 10 received sunitinib first line, and 2 patients received sorafenib as third-line therapy. Twenty-nine were evaluable for response rates. There were 10 patients (34%) who had stabilization of disease, 8 patients (28%) who had a partial response, and 11 patients (38%) who had progression of disease. The progression-free survival median was 8 months. Of the 34 patients evaluable for toxicities, grade 3 or 4 adverse event occurred in 19 patients (56%). These patients required either dose modifications and/or treatment interruptions within an average of the first 2 weeks of treatment. Eight patients (24%) required drug discontinuation. Eleven patients (32%) required dose reductions, but were able to resume the targeted dose after slow dose escalation. Three patients (9%) remain dose reduced for greater than 12 weeks. Conclusions: Sorafenib and sunitinib have extended patients' disease-free survival by several months; however, the initial grade 3 or 4 adverse event presented in the literature appear to have been under-reported. Our experience suggests that the first 4 weeks of treatment is the most likely timeframe within which drug reactions occur. Therefore, careful monitoring and possibly additional clinical visits are warranted during this time period. Although a significant percentage of patients require dose modification, many can be restarted and titrated up to the targeted dose.
引用
收藏
页码:217 / 220
页数:4
相关论文
共 16 条
[1]  
Amato RJ, 2007, J CLIN ONCOL, V25
[2]  
AWASA A, 2005, BRIT J CANCER, V92, P1855
[3]  
Choueiri TK, 2008, J CLIN ONCOL, V26, P127, DOI 10.1200/JCO.2007.13.3223
[4]   Risk of hand-foot skin reaction with sorafenibo: A systematic review and metes-analysis [J].
Chu, David ;
Lacouture, Mario E. ;
Fillos, Triantafillos ;
Wu, Shenhong .
ACTA ONCOLOGICA, 2008, 47 (02) :176-186
[5]   Safety and pharmacokinetics of the dual action Raf kinase and vascular endothelial growth factor receptor inhibitor, BAY 43-9006, in patients with advanced, refractory solid tumors [J].
Clark, JW ;
Eder, JP ;
Ryan, D ;
Lathia, C ;
Lenz, HJ .
CLINICAL CANCER RESEARCH, 2005, 11 (15) :5472-5480
[6]   Renal-cell carcinoma [J].
Cohen, HT ;
McGovern, FJ .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (23) :2477-2490
[7]   RETRACTED: Immunotherapy for advanced renal cell cancer - art. no. CD001425.pub2 (Retracted Article) [J].
Coppin, C ;
Porzsolt, F ;
Awa, A ;
Kumpf, J ;
Coldman, A ;
Wilt, T .
COCHRANE DATABASE OF SYSTEMATIC REVIEWS, 2005, (01)
[8]   Sorafenib in advanced clear-cell renal-cell carcinoma [J].
Escudier, Bernard ;
Eisen, Tim ;
Stadler, Walter M. ;
Szczylik, Cezary ;
Oudard, Stephane ;
Siebels, Michael ;
Negrier, Sylvie ;
Chevreau, Christine ;
Solska, Ewa ;
Desai, Apurva A. ;
Rolland, Frederic ;
Demkow, Tomasz ;
Hutson, Thomas E. ;
Gore, Martin ;
Freeman, Scott ;
Schwartz, Brian ;
Shan, Minghua ;
Simantov, Ronit ;
Bukowski, Ronald M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (02) :125-134
[9]   Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer [J].
Faivre, S ;
Delbaldo, C ;
Vera, K ;
Robert, C ;
Lozahic, S ;
Lassau, N ;
Bello, C ;
Deprimo, S ;
Brega, A ;
Massimini, G ;
Armand, JP ;
Scigalla, P ;
Raymond, E .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (01) :25-35
[10]   Cancer statistics, 2008 [J].
Jemal, Ahmedin ;
Siegel, Rebecca ;
Ward, Elizabeth ;
Hao, Yongping ;
Xu, Jiaquan ;
Murray, Taylor ;
Thun, Michael J. .
CA-A CANCER JOURNAL FOR CLINICIANS, 2008, 58 (02) :71-96