Abstract
BackgroundSurgical 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 methodsPatients 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.ResultsFifty-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.ConclusionsPatients 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 registrationClinicaltrials.gov, NCT01311050, registered March 6, 2011, retrospectively registered.
Highlights
Colorectal carcinoma (CRC) is the third most common malignancy worldwide and the second most common cause of cancer-related death in men and third in female [1]
Patients Patients with metastatic colorectal cancer (CRC) not amenable to surgical resection were enrolled in a phase I/II trial of triplet chemotherapy consisting of capecitabine, oxaliplatin, irinotecan, and bevacizumab [20]
Patients were considered ineligible if they had any of the following criteria: central nervous system metastasis, prior malignancy within 5 years, sever cardiovascular dysfunction, bleeding diathesis, major surgery within 28 days of starting therapy, active infection, uncontrolled hypertension, pregnancy or breastfeeding, and prior history of dihydropyrimidine deficiency
Summary
Colorectal carcinoma (CRC) is the third most common malignancy worldwide and the second most common cause of cancer-related death in men and third in female [1]. A significant percentage of patients have metastatic disease at initial presentation, with lung and liver being the most common sites of metastasis. Most of these patients have unresectable metastatic lesions, rendering the disease incurable [2]. Synchronous liver metastases have been reported in approximately 25% of patients diagnosed initially as colorectal cancer, while approximately 50% develop liver metastases during their disease course [3]. Chemotherapy has been proven to improve survival in patients with unresectable metastatic CRC. Surgical resection of metastatic disease in patients with initially non-resectable colorectal cancer (CRC) has improved overall survival. We report the result of combining intensive chemotherapy (triplet) and surgical resection of metastatic lesions in patients with metastatic CRC
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