BACKGROUND Surgical resection of metastatic disease in patients with initially non-resectable colorectal cancer (CRC) has improved overall survival . Intensified chemotherapy regimens have increased the probability of converting unresectable metastasis to resectable . Here, we report the result of combining intensive chemotherapy (triplet) and surgical resection of metastatic lesions in patients with metastatic CRC . PATIENTS AND
METHODS Patients with unresectable metastatic CRC were enrolled in phase I/II trial of triplet chemotherapy consisting of capecitabine, oxaliplatin, irinotecan, and bevacizumab . Patients were given 5-8 cycles induction chemotherapy of the above regimen followed by maintenance capecitabine and bevacizumab until disease progression, unacceptable toxicity, or patient request . All patients were assessed at a multidisciplinary conference for possible surgical resection of their metastatic disease at the time of inclusion in the trial and 2 monthly intervals thereafter . Patients who underwent R0 resection of their metastatic disease received adjuvant oxaliplatin and capecitabine to complete a total of 6 months of chemotherapy .
RESULTS Fifty-three patients were enrolled . The median age was 52 years (range 23-74), 29 (55 %) were males, ECOG PS 0-1 was 13 (66 %), 11 (42 %) had a right-sided tumor , 29 (55 %) had resection of their primary tumor , 22 (42 %) had a single metastatic site, and 8 (15.1 %) had a liver-limited disease . Thirteen patients (24.5 %) underwent surgical resection of residual metastatic disease +/- the primary tumor with 10 (18.9 %) of them were R0 . The surgical group had a higher incidence of males compared to the non-surgical group (69.3% vs 47.2%, p = 0.2), equal performance status, lower median number of metastatic sites (1 vs 2, p = 0.09), higher mutant Kras (53.8% vs 34.2%, p = 0.3), and higher response rate (84.6% vs 56.2%, p = 0.3). With a median follow-up duration of 89 months, the median PFS for the whole group was 16.1 months [95% confidence interval (CI) 9.1-20] and the median OS was 28.2 months (95% CI 22.5-53.3). The median PFS for the surgery group was 18.9 months (95% CI 12.6-not reached) compared to 9.6 months (95% CI 7.0-18.3) for the non-surgical group, log-rank p = 0.0165 . The median OS for both groups was not reached (95% CI 53.3-not reached) and 23.2 months (95% CI 17.0-28.4) respectively, log-rank p = 0.0006 . Five-year PFS and OS for the surgery group were 46.2% and 67.6% respectively .
CONCLUSIONS Patients with unresectable metastatic CRC and fit for triplet chemotherapy should have the benefit of combining this intensified regimen and surgical resection of their metastatic disease if possible .
TRIAL REGISTRATION Clinicaltrials.gov, NCT01311050, registered March 6 , 2011, retrospectively registered.