Nexavar(R) (sorafenib tosylate) geeft ook bescheiden doch goed resultaat bij nierkankerpatienten met uitzaaiingen t.o.v. placebo waar andere behandelingen faalden. Aldus kleine studie met 14 uitbehandelde nierkankerpatienten.

31 juli 2009: Bron: Medscape

Nadat grotere fase II en III studies bewezen hebben dat Nexavar(R) (sorafenib tosylate) een significant langere mediane overlevingstijd geeft bij nierkanker hebben onderzoekers Nexavar(R) (sorafenib tosylate) ook onderzocht als middel t.o.v. placebo bij nierkankerpatienten met uitgezaaide nierkanker waarbij andere behandelingen faalden. Van de 14 patienten kwam er 1 in een gedeeltelijke remissie (meer dan 50%) en 3 bewerkstelligden een stabiele ziekte. Volgens de onderzoekers is dit een bescheiden maar goed resultaat dat verder onderzoek vereist. Onder het abstract staat ook een referentielijst van belangrijke studies met Nexavar(R) (sorafenib tosylate).

Abstract

Background: In 2005, a phase III trial demonstrated a significant increase in progression-free survival in patients with renal cell cancer (RCC) treated with sorafenib versus placebo. While awaiting the full review by the US Federal Drug Administration, we initiated a treatment protocol as a mechanism for providing sorafenib to patients with advanced RCC but who were ineligible for other sorafenib clinical trials, also known as "compassionate use." In December 2005, sorafenib became commercially available, and this protocol was closed. Herein, we report our single-institution experience with this study.

Patients and Methods: Eligibility criteria included adults with advanced RCC with adequate organ function and performance status (PS). Treatment consisted of sorafenib 400 mg orally twice a day.

Results: We enrolled 14 patients. The median age was 64 years, and PS was 2. All had metastatic RCC that had progressed after a median of 2 therapies. One patient (7%) had a partial response, and 3 (21%) had stable disease, for a clinical benefit rate of 29%. Severe toxicities included 1 patient with each of grade 4 thrombocytopenia, grade 3 warfarin-induced coagulopathy (drug-to-drug interaction), hypertension, diarrhea, anorexia, nausea, rash, and headache. Five subjects received concomitant radiation therapy without unexpected toxicities.

Conclusion:

Sorafenib is a well-tolerated agent that has demonstrated antitumor activity in advanced RCC. Even pretreated subjects with multiple comorbidities can experience clinical benefit from sorafenib. Subjects receiving warfarin should be monitored closely for the development of coagulopathy. Severe hemoptysis can occur in patients with cavitary lung lesions. The combination of radiation therapy and sorafenib was safe, but larger studies should be performed before a wide recommendation can be made. Finally, we believe that most patients with advanced RCC should be enrolled into clinical trials because more effective treatments are urgently needed.

References

Jemal A, Siegel R, Ward E, et al. Cancer statistics 2008. CA Cancer J Clin 2008; 58:71-96.
Laber DA. Risk factors, classification and staging of renal cell cancer. Med Oncol 2006; 24:443-54.
Cohen D, Zhou M, Cohen D, et al. Molecular genetics of familial renal cell carcinoma syndromes. Clin Lab Med 2005; 25:259-77.
Awada A, Hendlisz A, Gil T, et al. Phase I safety and pharmacokinetics of BAY 439006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours. Br J Cancer 2005; 92:1855-61.
Moore M, Hirte HW, Siu L, et al. Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. Ann Oncol 2005; 16:1688-94.
Strumberg D, Richly H, Hilger RA, et al. Phase I clinical and pharmacokinetic study of the Novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol 2005; 23:965-72.
Ratain MJ, Eisen T, Stadler WM, et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 2006; 24:2505-12.
Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Eng J Med 2007; 356:125-34.
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 [see comment]. J Natl Cancer Inst 2000; 92:205-16.
Knox JJ, Figlin RA, Stadler WM, et al. The advanced renal cell carcinoma sorafenib (ARCCS) expanded access trial in North America: safety and efficacy. J Clin Oncol 2007: 25(18 suppl) 237s (Abstract 5011).
Common Terminology Criteria for Adverse Events v3.0 (CTCAE). Bethesda, MD: National Cancer Institute, 2003. Available at: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf. Accessed: December 31, 2008.
Nexavar (sorafenib) [prescribing information]. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2008. Available at: http://berlex.bayerhealthcare.com/html/ products/pi/Nexavar_PI.pdf. Accessed: December 31, 2008.
Data on File. Bayer Pharmaceuticals. NDA 15.6 (8.4.2.8.1).