Sorafenib Monotherapy In Patients With Metastatic Renal Cell Cancer: A Phase II Intra-Patient Dose Escalation Study

Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology;  Clinical Trials / Drug Trials
Article Date: 13 Apr 2008 - 0:00 PDT

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UroToday.com - Sorafenib 400 mg b.i.d. has shown anti-tumor activity and favorable tolerability in patients with metastatic renal cell carcinoma (RCC), allowing investigation of more intensive drug administration regimens. This titration study allowed individual patients to escalate to higher doses of sorafenib. Trial endpoints included response rate (RR), progression-free survival (PFS) and overall survival (OS).

Eligibility criteria: progressive measurable metastatic RCC; pathologic diagnosis of a component of clear cell disease; ≤1 prior cytokine therapy; Karnofsky performance status (KPS) ≥70%; adequate organ/marrow function; normal pancreatic/cardiac function, and no active CNS involvement. Escalation from Dose Level 1 (oral sorafenib 400 mg b.i.d.; day 1 - 28) could occur to Dose Level 2 (600 mg b.i.d; day 29 - 56) followed by Dose Level 3 (800 mg b.i.d.; day 57 onwards), dependent on adequate tolerability. Re-evaluation was performed every 8 weeks using RECIST.

Of 46 enrolled patients, 44 were evaluable (37:7 male:female; median age 50 years, range 43 - 79); 39 and 5 had a KPS of 100% and 90%, respectively. Sites of disease included lung, nodal, liver, bone, adrenal, pancreas and kidney. Patients had metastases at 1, 2 or 3+ sites (n=26, 11, and 7, respectively), and 19 had received prior therapy. Twelve patients continue to receive sorafenib therapy; 1 at 400mg/day, 1 at 800mg/day, 3 at 1200mg/day, and 7 at 1600mg/day. Response was seen in 24 patients: 7 complete response (CR) and 17 partial response (PR); and a further 9 patients achieved stable disease for 6+ months. Median PFS was 8.4+ months (range 3 - 17.4+ months) at the time of analysis. Treatment related adverse events included hand-foot skin reactions, skin rash, diarrhea, alopecia, fatigue, hypertension, hypophosphatemia, and elevated amylase/lipase.

The presentation concludes that Sorafenib dose escalation to 1200mg or 1600mg/day was achieved in 93% of patients with metastatic RCC. The CR/PR rate of 55%, and the prolonged median PFS of 8.4+ months, show that dose-escalated sorafenib has promising anti-tumor activity in this patient group.

Presented by: R. Amato, MD, et al, at the European Association of Urology - 23rd Annual EAU Congress - March 26 - 29, 2008 - Milan, Italy

Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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