To evaluate the overall response rate of patients with previously untreated unresectable liver-only metastases from colorectal cancer treated with neoadjuvant capecitabine and oxaliplatin plus bevacizumab.
No previous treatment. The 21 day cycle of treatment will be given for four courses before being reassessed by MRI/CT for resectability of their liver metastases. Those patients with stable disease or partial response, but are not yet resectable will continue for a further four courses of treatment before reassessment. Patients whose liver metastases have become resectable will proceed to surgery after a 6 week break from the last administration of Capecitabine (8 weeks from the last administration of Bevacizumab). A further four courses of treatment will be administered post-operatively to commence at least 8 weeks after surgery and when the patient is well recovered and healed.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
47
Capecitabine 1700mg/m2/day in two divided doses to be administered orally for 14 days followed by 7 days rest. For 4 courses initially. (For patients aged 75+ 1300mg/m2/day in two divided doses or 650mg/m2 twice daily) Courses as per detailed description above.
Oxaliplatin 130mg/m2 diluted in 5% dextrose will be given as an i.v. infusion over 2 hours. This will be administered on day 1 after bevacizumab. For 4 courses. (Patients aged 75+ should receive oxaliplatin at a reduced dose i.e. 100mg/m2) Courses as per detailed description above.
Bevacizumab at a dose of 7.5 mg/kg, diluted in normal saline, will be administered as an iv infusion over 30 to 90 minutes before the administration of oxaliplatin on day 1 of every cycle. The first infusion should be administered over 90 minutes. If well tolerated, the second infusion can be administered over 60 minutes. Provided that this is tolerated subsequent infusions can be administered over 30 minutes. If a patient experiences an infusion related adverse event with the 60 minute infusion, all subsequent infusions will be administered over 90 minutes. If a patient experiences an infusion related reaction with the 30 minute infusion, all subsequent infusions will be administered over 60 minutes Courses as per detailed description above.
David Cunningham
Sutton, Surrey, United Kingdom
Overall response rates
Time frame: 12 months
Complete resection (R0) rate
Time frame: 12 months
Safety and feasibility of adding bevacizumab to neoadjuvant capecitabine and oxaliplatin in patients undergoing liver metastasectomy
Time frame: 12 months
Other parameters of efficacy (response and survival) in patients with unresectable liver-only metastases treated with this neoadjuvant combination
Time frame: 5 years
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Patients with liver metastases which have become resectable and in whom surgery is still deemed appropriate should proceed to surgery after a 6 week interval from the last administration of capecitabine chemotherapy (at least 8 weeks from last administration of bevacizumab).