No 50 43 36 32 4 2 5 Page 4 of 10 100 86 5 12 84 (CI ± 11) 75 9 Intent-to-treat Analysis No % As-treated Analysis % 50 49 40 36 4 2 7 12 3-46+ 38 28 3-47 28 13 100 98 82 (CI ± 11) 73 8 4 14 76 56 26 39 54 Bruera et al. BMC Cancer 2010, 10:567 http://www.biomedcentral.com/1471-2407/10/567 Table 2 Activity and efficacy data Enrolled patients Evaluable patients Objective Response Partial Response Complete Response Stable Disease Progressive Disease Median Progression-free survival, months Range Progression events Median Overall Survival, months Range Deaths Liver metastasectomies No/Overall patients (50) No/Patients with liver metastases (33) No/Patients with liver-only metastases (22) stable diseases (4%); 7 progressive diseases (14%). Disease control rate was 86% (a 0.05, CI ± 10). In the as-treated analysis, 43 pts were evaluable: 6 pts did not receive at least three cycles of treatment, due to limiting gastrointest- inal toxicity (3 patients) requiring treatment discontinua- tion in 2 of these, surgical resection of liver metastasis (1 patient) and of local recurrence (1 patient), clinical evi- dence of progressive disease (1 patient). ORR was 84% (a 0.05, CI ± 11). We observed 36 objective responses: 32 partial responses (75%) and 4 CR (9%); 2 stable diseases (5%); 5 progressive diseases (12%). Disease control rate was 88% (a 0.05, CI ± 10). After a median follow-up of 21 months (Figure 1), median PFS was 12 months (3-46+): 38 events occurred and 12 pts (24%) were progression-free > 12 months. Median OS was 28 months (3-47): 28 events occurred and 22 pts (44%) were alive; 80% of pts (40 pts) were alive > 12 months. Among the 24 young-elderly pts, in the intent-to-treat analysis, ORR was 79% (a 0.05, CI ± 12): 16 partial responses (67%) and 3 CR (12.5%); 5 progressive disease (21%). In the as-treated analysis, 20 young-elderly pts were evaluable; ORR was 80% (a 0.05, CI ± 12). After a median follow-up of 18.5 months, median PFS was 11 months (3-46+): 20 events occurred and 4 pts were pro- gression-free. Median OS was 20 months (6-46+): 16 events occurred and 8 pts were alive. Liver metastasectomies were performed in 13 pts of the 50 enrolled pts (26%); 13 of the 33 pts with liver metastases (39%) (Table 2). Twelve metastasectomies out of 22 pts with liver-only metastases (54%) were per- formed: 6 in 9 pts with single liver metastasis (66%); 6 in 13 pts with multiple liver metastases (46%). In one patient with single liver metastasis associated with lung metastases, double metastatic resections were per- formed. Overall, R0 liver resections were 11 (84.6%), R1 resections were 2 (15.4%). Among the 22 pts with liver- only metastases, 5 pts had initially resectable disease (23%), 2 metastasectomies were performed and 2 pts showed a cCR; 6 pts had initially unresectable disease (27%), 3 metastasectomies were performed and 1 patient showed a cCR; 11 pts (50%) had potentially resectable liver metastases and 7 metastasectomies were per- formed. No surgery-related complications were reported. Hepatic steatosis was observed in 3 pts (25%). Liver metastases showed necrotic areas between 10 and 100% in 6 pts (50%). In 2 pts with multiple liver-only metas- tases a pathologic CR was obtained (6% of pts with liver metastases and 15% of liver metastasectomies). Overall, 4 clinical and 2 pathologic CRs (12.5%) were reported; 1 patient showed a progressive disease at 17 months; 5 pts were progression-free at 46, 37, 19, 17 and 12 months, respectively. Twenty-six pts (52%) received, at least, a second line treatment: FIr-B/FOx association in 4 pts (8%), who showed a long-lasting PFS; Cetuximab-containing treat- ment in 15 pts (30%): Bev-containing in 2 pts (4%); triplet- chemotherapy (FIr-FOx) in 1 patient (2%); Panitumumab in 1 patient (2%); Capecitabine alone in 3 pts (6%). Dose-intensity Median number of administered cycles was 5 (range 2-9).