Top

Journal of Cancer Research and Clinical Oncology

Published in:

01-03-2010 | Original Paper

Efficacy of targeted therapy in patients with renal cell carcinoma with pre-existing or new bone metastases

Authors: Jakub Żołnierek, Pawel Nurzyński, Przemysław Langiewicz, Sylwia Oborska, Anna Waśko-Grabowska, Ewa Kuszatal, Beata Obrocka, Cezary Szczylik

Published in: Journal of Cancer Research and Clinical Oncology | Issue 3/2010

Abstract

Introduction

This single-centre retrospective analysis of data from three randomised studies and two expanded-access studies compared the effect of interferon (IFN)-alfa, sunitinib, and sorafenib on the occurrence and progression of metastatic bone lesions in patients with renal cell carcinoma (RCC).

Methods

The analysis included 292 patients: 107 received sunitinib 50 mg/day in 6-week cycles (Schedule 4/2), 147 received sorafenib 800 mg/day, and 38 received placebo or IFN-alfa 9 MU t.i.w.

Results

Pre-existing metastatic bone lesions were reported in 82 patients, of which 30 experienced progression. Twenty-three of 210 patients developed new bone lesions. Overall, sunitinib appeared slightly more effective than sorafenib or IFN-alfa at extending mean time to progression of pre-existing bone lesions (P = 0.057). Compared with sorafenib, sunitinib significantly decreased formation (P = 0.034) and prolonged time to occurrence of new bone lesions (P = 0.047).

Conclusion

Further evaluation of the effect of these therapies on bone metastases in RCC is warranted.

Abrams TJ, Lee LB, Murray LJ, Pryer NK, Cherrington JM (2003) SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. Mol Cancer Ther 2:471–478PubMed

Beeram M, Patnaik A, Rowinsky EK (2005) Raf: a strategic target for therapeutic development against cancer. J Clin Oncol 23:6771–6790CrossRefPubMed

Bukowski R, Szczylik C, Stadler W, Simantov R, Shan M (2007) Final results of the randomized phase III trial of sorafenib in advanced renal cell carcinoma: survival and biomarker analysis. J Clin Oncol 25(18S):240s (Abstract 5023)

Coleman RE (1997) Skeletal complications of malignancy. Cancer 80:1588–1594CrossRefPubMed

Costa L, Major PP (2009) Effect of bisphosphonates on pain and quality of life in patients with bone metastases. Nat Clin Pract Oncol 6:163–174CrossRefPubMed

Escudier B, Szczylik C, Eisen T, Stadler WM, Schwartz B, Shan M, Bukowski RM (2005) Randomized phase III trial of the Raf kinase and VEGFR inhibitor sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC). J Clin Oncol 23(16S):380s (Abstract LBA4510)

Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134CrossRefPubMed

Godley P, Taylor M (2001) Renal cell carcinoma. Curr Opin Oncol 13:199–203CrossRefPubMed

Gore M, Szczylik C, Porta C, Bracarda S, Hawkins R, Bjarnason G, Oudard S, Lee SH, Haanen J, Castellano D, Vrdoljak E, Schoffski P, Mainwaring P, Nieto A, Yuan J, Bukowski R (2009) Safety and efficacy of sunitinib with subpopulation analysis in an expanded-access trial of metastatic renal cell carcinoma. Lancet Oncol 10:757–763CrossRefPubMed

Janzen NK, Kim HL, Figlin RA, Belldegrun AS (2003) Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol Clin North Am 30:843–852CrossRefPubMed

Kim DW, Jo YS, Jung HS, Chung HK, Song JH, Park KC, Park SH, Hwang JH, Rha SY, Kweon GR, Lee SJ, Jo KW, Shong M (2006) An orally administered multitarget tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases. J Clin Endocrinol Metab 91:4070–4076CrossRefPubMed

Kominsky SL, Doucet M, Brady K, Weber KL (2007) TGF-β promotes the establishment of renal cell carcinoma bone metastasis. J Bone Miner Res 21:37–44CrossRef

Lilleby W, Fossa SD (2005) Chemotherapy in metastatic renal cell cancer. World J Urol 23:175–179CrossRefPubMed

Ljungberg B, Hanbury D, Kuczyk M (2007) Renal cell carcinoma guideline. Eur Urol 51:1502–1510CrossRefPubMed

Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, Schreck RE, Abrams TJ, Ngai TJ, Lee LB, Murray LJ, Carver J, Chan E, Moss KG, Haznedar JO, Sukbuntherng J, Blake RA, Sun L, Tang C, Miller T, Shirazian S, McMahon G, Cherrington JM (2003) In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 9:327–337PubMed

Motzer RJ, Bander NH, Nanus DM (1996) Renal-cell carcinoma. N Engl J Med 335:865–875CrossRefPubMed

Motzer RJ, Rini BI, Bukowski RM, Curti BD, George DJ, Hudes GR, Redman BG, Margolin KA, Merchan JR, Wilding G, Ginsberg MS, Bacik J, Kim ST, Baum CM, Michaelson MD (2006) Sunitinib in patients with metastatic renal cell carcinoma. JAMA 295:2516–2524CrossRefPubMed

Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124CrossRefPubMed

Mundy GR (2002) Metastasis to bone: causes, consequences and therapeutic opportunities. Nature 2:584–593

Negrier S, Escudier B, Gomez F, Douillard JY, Ravaud A, Chevreau C, Buclon M, Perol D, Lasset C (2002) Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Francais d’Immunotherapie. Ann Oncol 13:1460–1468CrossRefPubMed

O’Farrell AM, Abrams TJ, Yuen HA, Ngai TJ, Louie SG, Yee KW, Wong LM, Hong W, Lee LB, Town A, Smolich BD, Manning WC, Murray LJ, Heinrich MC, Cherrington JM (2003) SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 101:3597–3605CrossRefPubMed

Plastaras JP, Kim S-H, Liu YY, Dicker DT, Dorsey JF, McDonough J, Cerniglia G, Rajendran RR, Gupta A, Rustgi AK, Diehl JA, Smith CD, Flaherty KT, El-Deiry WS (2007) Cell cycle-dependent and schedule-dependent antitumour effects of sorafenib combined with radiation. Cancer Res 67:9443–9454CrossRefPubMed

Ratain MJ, Eisen T, Stadler WM, Flaherty KT, Kaye SB, Rosner GL, Gore M, Desai AA, Patnaik A, Xiong HQ, Rowinsky E, Abbruzzese JL, Xia C, Simantov R, Schwartz B, O’Dwyer PJ (2006) Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 24:2505–2512CrossRefPubMed

Rohrmann K, Staehler M, Haseke N, Bachmann A, Stief CG, Siebels M (2005) Immunotherapy in metastatic renal cell carcinoma. World J Urol 23:196–201CrossRefPubMed

Ryan CW, Bukowski RM, Figlin R, Knox J, Hutson TE, Dutcher JP, George J, Kirshner J, Humphrey J, Stadler WM, On behalf of the ARCCS Investigators (2007) The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) expanded access trial: Long-term outcomes in first-line patients (pts). J Clin Oncol 25(18S):258s (Abstract 5096)

Sachdeva K, Makhoul I, Javeed M, Curti B (2008) Renal cell carcinoma. eMedicine http://www.emedicine.com/MED/topic2002.htm, 1–23

Schoffski P, Dumez H, Clement P, Hoeben A, Prenen H, Wolter P, Joniau S, Roskams T, Van PH (2006) Emerging role of tyrosine kinase inhibitors in the treatment of advanced renal cell cancer: a review. Ann Oncol 17:1185–1196CrossRefPubMed

Staehler M, Haseke N, Stadler T, Karl A, Stief CG, Wilkowski R (2009) Effectivity of radiation therapy in combination with multi-kinase inhibition based on sorafenib or sunitinib in progressive metastatic renal cancer. Eur Urol Suppl 8:156 (Abstract 143)CrossRef

Szczylik C, Demkow T, Staehler M, Rolland F, Negrier S (2007) Randomized phase II trial of first line treatment with sorafenib versus interferon in patients with advanced renal cell carcinoma: final results. J Clin Oncol 25(18S):241s (Abstract 5025)

Taussky D, Soulières D (2009) Hypofractionated radiotherapy with concomitant sunitinib—is there a radiosensitizing effect? Can J Urol 16:4599–4600PubMed

Weber KL, Doucet M, Price JE, Baker C, Kim SJ, Fidler IJ (2003) Blockade of epidermal growth factor receptor signaling leads to inhibition of renal cell carcinoma growth in the bone of nude mice. Cancer Res 63:2940–2947PubMed

Wilhelm S, Chien DS (2002) BAY 43-9006: preclinical data. Curr Pharm Des 8:2255–2257CrossRefPubMed

Zekri J, Ahmed N, Coleman RE, Hancock B (2001) The skeletal metastatic complications of renal cell carcinoma. Int J Oncol 19:379–382PubMed

Title: Efficacy of targeted therapy in patients with renal cell carcinoma with pre-existing or new bone metastases
Authors: Jakub Żołnierek
Pawel Nurzyński
Przemysław Langiewicz
Sylwia Oborska
Anna Waśko-Grabowska
Ewa Kuszatal
Beata Obrocka
Cezary Szczylik
Publication date: 01-03-2010
Publisher: Springer-Verlag
Published in: Journal of Cancer Research and Clinical Oncology / Issue 3/2010
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-009-0664-7

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Efficacy of targeted therapy in patients with renal cell carcinoma with pre-existing or new bone metastases

Abstract

Introduction

Methods

Results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2010

Mina53, a novel c-Myc target gene, is frequently expressed in lung cancers and exerts oncogenic property in NIH/3T3 cells

Identification of potential serum markers for endometrial cancer using protein expression profiling

Fragile histidine triad protein: structure, function, and its association with tumorogenesis

SFRP4 was overexpressed in colorectal carcinoma

Serum CA 125 expression as a tumor marker for diagnosis and monitoring the clinical course of epithelioid sarcoma

Hypoxia induced paclitaxel resistance in human ovarian cancers via hypoxia-inducible factor 1α

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page