Korean J Urol.  2010 Jun;51(6):379-385.

Comparative Analysis between Immunochemotherapy and Target Therapy for Metastatic Renal Cell Carcinoma: Overview of Treatment-Related Adverse Events and the Dropout Rate in Korea

• Lee JH
• Chang SG
• Jeon SH
• Min GE
• Yoo KH

Abstract

PURPOSE
To comparatively analyze treatment-related adverse events and the treatment dropout rate between immunochemotherapy and target therapy in Korea.
MATERIALS AND METHODS
Forty-nine subjects with metastatic renal cell carcinoma (21 target therapy recipients and 28 immunochemotherapy recipients) who underwent either 6-week cycles of sunitinib treatment (50 mg once daily for 4 weeks on and 2 weeks off) or 8-week cycles of immunochemotherapy (combination of interleukin [IL]-2, interferon [IFN]-alpha, and 5-fluorouracil [FU]) were enrolled. Treatment-related toxicity was objectively graded and quantitative analysis was performed with a scoring system. Patient compliance was categorized into three classes (1: administration as scheduled, 2: dose modification required, 3: discontinuation required).
RESULTS
Compared with those of the immunochemotherapy group, subjects of the sunitinib-treatment group had higher occurrence rates of mucositis-stomatitis (43% vs. 10%), hand-foot syndrome (38% vs. 0%), diarrhea (33% vs. 14%), and hypertension (33% vs. 14%). According to the toxicity-grade-based scoring system, the total incidence and severity of toxicities were not significantly different between the two groups (p>0.05), whereas high-grade hematologic toxicities were more frequent in the immunochemotherapy group. The dropout rate of the immunochemotherapy group was significantly higher than that of the sunitinib group (administration as scheduled: 52% vs. 21%, p=0.026; discontinuation required: 19% vs. 50%, p=0.037).
CONCLUSIONS
The results of this study are indicative of a comparable treatment-related toxicity profile of sunitinib and greater adherence to the treatment protocol in comparison with immunochemotherapy in patients with metastatic renal cell carcinoma (mRCC).

Keyword

Immunotherapy; Sunitinib; Toxicity

MeSH Terms

Carcinoma, Renal Cell
Clinical Protocols
Diarrhea
Fluorouracil
Hand-Foot Syndrome
Humans
Hypertension
Immunotherapy
Incidence
Indoles
Interferons
Interleukins
Korea
Patient Compliance
Patient Dropouts
Pyrroles
Fluorouracil
Indoles
Interferons
Interleukins
Pyrroles

Reference

1. Jayson M, Sanders H. Increased incidence of serendipitously discovered renal cell carcinoma. Urology. 1998; 51:203–205. PMID: 9495698.

2. Motzer RJ, Russo P. Systemic therapy for renal cell carcinoma. J Urol. 2000; 163:408–417. PMID: 10647643.

3. Herrmann E, Bierer S, Wülfing C. Update on systemic therapies of metastatic renal cell carcinoma. World J Urol. 2010; 28:303–309. PMID: 20180125.

4. Kollmannsberger C, Soulierers D, Wong R, Scalera A, Gaspo R, Bjarnason G. Sunitinib therapy for metastatic renal cell carcinoma: recommendations for management of side effects. Can Urol Assoc J. 2007; 1(2 Suppl):S41–S54. PMID: 18542784.

5. Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA, et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006; 24:16–24. PMID: 16330672.

6. Hong MH, Kim HS, Kim C, Ahn JR, Chon HJ, Shin SJ, et al. Treatment outcome of sunitinib treatment in advanced renal cell carcinoma patients: a single cancer center experience in Korea. Cancer Res Treat. 2009; 41:67–72. PMID: 19707503.

7. Song CR, Ahn HJ, Kim CS. Factors modulating response to immunonchemotherapy in advanced renal cell carcinomas. Korean J Urol. 2002; 43:913–918.

8. Atzpodien J, Kirchner H, Duensing S, Lopez Hanninen E, Franzke A, Buer J, et al. Biochemotherapy of advanced metastatic renal-cell carcinoma: results of the combination of interleukin-2, alpha-interferon, 5-fluorouracil, vinblastine and 13-cis-retinoic acid. World J Urol. 1995; 13:174–177. PMID: 7550391.

9. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, 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. 2000; 92:205–216. PMID: 10655437.

10. Baluna R, Vitetta ES. Vascular leak syndrome: a side effect of immunotherapy. Immunopharmacology. 1997; 37:117–132. PMID: 9403331.

11. Adams VR, Leggas M. Sunitinib malate for the treatment of metastatic renal cell carcinoma and gastrointestinal tumors. Clin Ther. 2007; 29:1338–1353. PMID: 17825686.

12. Motzer RJ, Michaelson MD, Rosenberg J, Bukowski RM, Curti BD, George DJ, et al. Sunitinib efficacy against advanced renal cell carcinoma. J Urol. 2007; 178:1883–1887. PMID: 17868732.

13. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, et al. Sunitinib versus interferon alpha in metastatic renal-cell carcinoma. N Engl J Med. 2007; 356:115–124. PMID: 17215529.

14. Motzer RJ, Bukowski RM. Targeted therapy for metastatic renal cell carcinoma. J Clin Oncol. 2006; 24:5601–5608. PMID: 17158546.

15. Hutson TE, Figlin RA, Kuhn JG, Motzer RJ. Targeted therapies for metastatic renal cell carcinoma: an overview of toxicity and dosing strategies. Oncologist. 2008; 13:1084–1096. PMID: 18838439.

16. van der Veldt AA, Boven E, Helgason HH, van Wouwe M, Berkhof J, de Gast G, et al. Predictive factors for severe toxicity of sunitinib in unselected patients with advanced renal cell cancer. Br J Cancer. 2008; 99:259–265. PMID: 18594533.

17. Bhojani N, Jeldres C, Patard JJ, Perrotte P, Suardi N, Hutterer G, et al. Toxicities associated with the administration of sorafenib, sunitinib, and temsirolimus and their management in patients with metastatic renal cell carcinoma. Eur Urol. 2008; 53:917–930. PMID: 18054825.

18. Rini BI, Tamaskar I, Shaheen P, Salas R, Garcia J, Wood L, et al. Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst. 2007; 99:81–83. PMID: 17202116.

19. Chu TF, Rupnick MA, Kerkela R, Dallabrida SM, Zurakowski D, Nguyen L, et al. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet. 2007; 370:2011–2019. PMID: 18083403.

20. Cella D, Li JZ, Cappelleri JC, Bushmakin A, Charbonneau C, Kim ST, et al. Quality of life in patients with metastatic renal cell carcinoma treated with sunitinib or interferon alpha: results from a phase III randomized trial. J Clin Oncol. 2008; 26:3763–3769. PMID: 18669464.