Sorafenib (S) plus gemcitabine (GEM) and capecitabine (CAP) for advanced renal cell carcinoma (RCC): Updated phase I results from a phase I/II trial (NCI 6981)

16023 Background: While RCC is often considered chemo-resistant, the combination of GEM and 5-FU or CAP has activity. S improves progression free survival and is well-tolerated, but has limited response rates and patients (pts) progress at a median of 6 months. We chose to study the combination of S plus GEM and CAP. Methods: Cohorts of 3–6 pts were treated with S, GEM and CAP to establish dose limiting toxicity (DLT) and the maximum tolerated dose (MTD). After 2 of the initial 4 pts developed DLT (grade 3 hand/foot), the protocol was amended and the initial CAP dose was lowered. A subsequent amendment allowed one prior anti-angiogenic therapy. Results: 15 pts (median age 56) were enrolled with the following characteristics: 7 ECOG PS 0, 4 PS 1, 4 PS 2; 5 MSK good risk, 6 intermediate, and 4 poor risk; 14 of 15 clear cell variant (3 with sarcomatoid differentiation), 1 papillary variant; 40% with liver involvement and 40% with bone metastases; 13 pts were treatment naive, 1 progressed on cytokines and 1 o...