We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

A Phase II trial of dosage escalation of sorafenib in Asian patients with metastatic renal cell carcinoma

    Hong-kai Wang

    Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Authors contributed equally

    Search for more papers by this author

    ,
    Hai-liang Zhang

    Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Authors contributed equally

    Search for more papers by this author

    ,
    Yao Zhu

    Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    ,
    Xu-dong Yao

    Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    ,
    Shi-lin Zhang

    Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    ,
    Bo Dai

    Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    ,
    Yi-jun Shen

    Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    ,
    Yi-ping Zhu

    Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    ,
    Guo-hai Shi

    Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    ,
    Xiao-jian Qin

    Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    ,
    Chun-guang Ma

    Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    ,
    Guo-wen Lin

    Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    ,
    Wen-jun Xiao

    Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    &
    Ding-wei Ye

    *Author for correspondence:

    E-mail Address: dwyeli@163.com

    Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Published Online:https://doi.org/10.2217/fon.14.131

    ABSTRACT 

    Aim: To investigate the role of sorafenib dosage escalation in Asian patients with metastatic renal cell carcinoma that had progressed after routine dosages. Patients & methods: Sorafenib dosage escalation to 600 or 800 mg twice a day was offered to 41 patients with metastatic renal cell carcinoma who had progressed on normal dosages. Clinical outcome, toxicity and favorable clinical covariables for progression-free survival (PFS) were evaluated. Results: The median PFS with dosage-escalated therapy was 7 months. Drug-related adverse events were tolerable. The pre-escalation Karnofsky performance status, serum calcium concentration, neutrophil/lymphocyte ratio, PFS and the highest toxicity grade at the routine dosage were associated with a longer PFS in the dosage-escalation period. Conclusion: Sorafenib dosage escalation was efficacious and tolerable in Asian patients. Trial registration: Chinese Clinical Trial Registry (no. ChiCTR-ONRC-12002088).

    Papers of special note have been highlighted as: • of interest; •• of considerable interest.

    References

    • 1 Wilhelm SM, Carter C, Tang L et al. BAY 43–9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 64(19), 7099–7109 (2004).
    • 2 Escudier B, Szczylik C, Hutson TE et al. Randomized Phase II trial of first-line treatment with sorafenib versus interferon alfa-2a in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 27(8), 1280–1289 (2009). •• Results from this randomized clinical trial demonstrated the benefit of a dosage escalation strategy after failure at routine dosages.
    • 3 Amato RJ, Harris P, Dalton M et al. A Phase II trial of intra-patient dose-escalated sorafenib in patients (pts) with metastatic renal cell cancer (mRCC). J. Clin. Oncol. 25(Suppl. 18), Abstract 5026 (2007). •• This study used a different escalation strategy and observed a promising complete and partial response rate and prolonged progression-free survival in specific patients.
    • 4 Strumberg, D, Clark JW, Awada A et al. Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: a review of four Phase I trials in patients with advanced refractory solid tumors. Oncologist 12(4), 426–437 (2007).
    • 5 Escudier B, Eisen T, Stadler WM et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N. Engl. J. Med. 356(2), 125–134 (2007). • A landmark Phase III trial of sorafenib in patients with renal cell carcinoma (RCC).
    • 6 Naito S, Tsukamoto T, Murai M, Fukino K, Akaza H. Overall survival and good tolerability of long-term use of sorafenib after cytokine treatment: final results of a Phase II trial of sorafenib in Japanese patients with metastatic renal cell carcinoma. BJU Int. 108(11), 1813–1819 (2011).• A Phase II clinical trial from Japan indicating good tolerability and prolonged survival of Asian patients with metastatic RCC.
    • 7 Zhang H, Dong B, Lu JJ et al. Efficacy of sorafenib on metastatic renal cell carcinoma in Asian patients: results from a multicenter study. BMC Cancer 9, 249 (2009).
    • 8 Therasse P, Arbuck SG, Eisenhauer EA et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J. Natl Cancer Inst. 92(3), 205–216 (2000).
    • 9 Orrell DH. Albumin as an aid to the interpretation of serum calcium. Clin. Chim. Acta 35(2), 483–489 (1971).
    • 10 Motzer RJ, Hutson TE, Tomczak P et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N. Engl. J. Med. 356(2), 115–124 (2007).
    • 11 Escudier B, Pluzanska A, Koralewski P et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind Phase III trial. Lancet 370(9605), 2103–2111 (2007).
    • 12 Sternberg CN, Davis ID, Mardiak J et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized Phase III trial. J. Clin. Oncol. 28(6), 1061–1068 (2010).
    • 13 Chang YS, Adnane J, Trail PA et al. Sorafenib (BAY 43-9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models. Cancer Chemother. Pharmacol. 59(5), 561–574 (2007).
    • 14 Mancuso A, Di Paola ED, Leone A et al. Phase II escalation study of sorafenib in patients with metastatic renal cell carcinoma who have been previously treated with anti-angiogenic treatment. BJU Int. 109(2), 200–206 (2012).
    • 15 Motzer RJ, Bacik J, Schwartz LH et al. Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J. Clin. Oncol. 22(3), 454–463 (2004).
    • 16 Heng DY, Xie W, Regan MM et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J. Clin. Oncol. 27(34), 5794–5799 (2009). •• This study identified some possible prognostic factors for treatment outcome in patients with metastatic RCC treated with targeted therapy agents.
    • 17 Ohno Y, Nakashima J, Ohori M, Hatano T, Tachibana M. Pretreatment neutrophil-to-lymphocyte ratio as an independent predictor of recurrence in patients with nonmetastatic renal cell carcinoma. J. Urol. 184(3), 873–878 (2010).
    • 18 Ohno Y, Nakashima J, Ohori M, Gondo T, Hatano T, Tachibana M. Followup of neutrophil-to-lymphocyte ratio and recurrence of clear cell renal cell carcinoma. J. Urol. 187(2), 411–417 (2012).
    • 19 Zahorec R. Ratio of neutrophil to lymphocyte counts – rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl. Lek. Listy 102(1), 5–14 (2001).
    • 20 Gore ME, Szczylik C, Porta C et al. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol. 10(8), 757–763 (2009).
    • 21 Bono P, Rautiola J, Utriainen T, Joensuu H. Hypertension as predictor of sunitinib treatment outcome in metastatic renal cell carcinoma. Acta Oncol. 50(4), 569–573 (2011).
    • 22 Hudes G, Carducci M, Tomczak P et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N. Engl. J. Med. 356(22), 2271–2281 (2007).
    • 23 Tanigawa G, Kawashima A, Yamaguchi S et al. Clinical outcome and prognostic factors of sorafenib in Japanese patients with advanced renal cell carcinoma in general clinical practice. Jpn J. Clin. Oncol. 41(11), 1265–1270 (2011).
    • 24 Ueda T, Imamura Y, Komaru A et al. Treatment outcomes of sorafenib for first line or cytokine refractory advanced renal cell carcinoma in Japanese patients. Int. J. Urol. 17(9), 811–815 (2010).
    • 25 Yang L, Shi L, Fu Q et al. Efficacy and safety of sorafenib in advanced renal cell carcinoma patients: results from a long-term study. Oncol. Lett. 3(4), 935–939 (2012).
    • 26 Park SJ, Lee JL, Park I et al. Comparative efficacy of sunitinib versus sorafenib as first-line treatment for patients with metastatic renal cell carcinoma. Chemotherapy 58(6), 468–474 (2012).
    • 27 Zama IN, Hutson TE, Elson P et al. Sunitinib rechallenge in metastatic renal cell carcinoma patients. Cancer 116(23), 5400–5406 (2010).
    • 28 Rini BI, Melichar B, Ueda T et al. Axitinib with or without dose titration for first-line metastatic renal-cell carcinoma: a randomised double-blind Phase 2 trial. Lancet Oncol. 14(12), 1233–1242 (2013).