A phase II trial of gemcitabine plus capecitabine (GX) in patients with advanced renal cell cancer (mRCC) previously treated with immunotherapy.

4598 Background: There is no standard therapy for pts with mRCC who develop progressive disease (PD) after immunotherapy. Novel molecular targeting agents are showing promising results but their full impact is still evolving. A phase II study of GX by CALGB produced modest activity and toxicity greater than expected. (WM Stadler et al, Abstract 4515 ASCO proceedings 2004) Methods: 81 pts (63 males, 18 females) with previously treated mRCC received GX as follows: G 1000 mg/m IV on days 1, 8, 15; X 830 mg/m po bid x 21 days; cycles repeated q 28 days. Cycles were interrupted for dose-limiting toxicity with dose reductions applied for subsequent cycles. The primary endpoint of the study is progression-free survival (PFS). Secondary endpoints are response rate (RR), overall survival (OS) and toxicity.,81 pts are evaluable for toxicity and 75 pts are evaluable for response. Median age is 61 yrs (35-76). Performance score (PS) 0 (14 pts), PS 1 (54 pts), PS 2 (13 pts). Number of prior therapies: 1 (55 pts), 2 (18 pts), 3 (3 pts). Prior therapy: high-dose IL-2 (13 pts); the rest had IFN +/- IL-2 +/- experimental agents. Number of metastatic sites: 1 (15 pts), 66 pts had ≥ 2. There are 7 partial responses (10%). Median PFS is 4.9 mos (95% CI 3.5-9.4). Median OS has not been reached yet (14+ mos). 14 pts have died of PD. 61 pts had interruption of therapy and dose reduction at least once. Of 371 cycles delivered, toxicities observed include grade 3/4 neutropenia (17.7%), grade 2-4 thrombocytopenia (6.7%), grade 2/3 anemia (2.2%), grade 2/3 hand-foot syndrome (8.6%), grade 2/3 mucositis (4.3%), grade 2/3 nausea/vomiting (2.7%), grade 2/3 diarrhea (2.2%), grade 2/3 infections (1.9%). 10 pts had grade 2/3 fatigue, 1 pt had grade 4 fatigue, 7 pts had deep vein thrombosis, 2 pts had pulmonary embolism, 2 pts had hematuria. There were no therapy-related deaths.,GX has modest activity in mRCC and could be used in combination with targeted therapy, but the dose/schedule used in this study have to be modified. [Table: see text].