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Clinical Trial
. 2009 May 20:9:156.
doi: 10.1186/1471-2407-9-156.

A phase II experience with neoadjuvant irinotecan (CPT-11), 5-fluorouracil (5-FU) and leucovorin (LV) for colorectal liver metastases

Oliver F Bathe  1 , Scott Ernst, Francis R Sutherland, Elijah Dixon, Charles Butts, David Bigam, David Holland, Geoffrey A Porter, Jennifer Koppel, Scot Dowden
Affiliations
Clinical Trial

A phase II experience with neoadjuvant irinotecan (CPT-11), 5-fluorouracil (5-FU) and leucovorin (LV) for colorectal liver metastases

Oliver F Bathe et al. BMC Cancer. .

Abstract

Background: Chemotherapy may improve survival in patients undergoing resection of colorectal liver metastases (CLM). Neoadjuvant chemotherapy may help identify patients with occult extrahepatic disease (averting unnecessary metastasectomy), and it provides in vivo chemosensitivity data.

Methods: A phase II trial was initiated in which patients with resectable CLM received CPT-11, 5-FU and LV for 12 weeks. Metastasectomy was performed unless extrahepatic disease appeared. Postoperatively, patients with stable or responsive disease received the same regimen for 12 weeks. Patients with progressive disease received either second-line chemotherapy or best supportive care. The primary endpoint was disease-free survival (DFS); secondary endpoints included overall survival (OS) and safety.

Results: 35 patients were accrued. During preoperative chemotherapy, 16 patients (46%) had grade 3/4 toxicities. Resection was not possible in 5 patients. One patient died of arrhythmia following surgery, and 1 patient had transient liver failure. During the postoperative treatment phase, 12 patients (55%) had grade 3/4 toxicities. Deep venous thrombosis (DVT) occurred in 11 patients (34%) at various times during treatment. Of those who underwent resection, median DFS was 23.0 mo. and median OS has not been reached. The overall survival from time of diagnosis of liver metastases was 51.6 mo for the entire cohort.

Conclusion: A short course of chemotherapy prior to hepatic metastasectomy may serve to select candidates best suited for resection and it may also direct postoperative systemic treatment. Given the significant incidence of DVT, alternative systemic neoadjuvant regimens should be investigated, particularly those that avoid the use of a central venous line.

Trial registration: ClinicalTrials.gov NCT00168155.

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Figures

Figure 1
Figure 1
Distribution of patients who received each phase of treatment.
Figure 2
Figure 2
Kaplan-Meier curves illustrating disease-free survival (A) and overall survival (B) from time of diagnosis, in patients who underwent liver resection.
Figure 3
Figure 3
A Kaplan-Meier curve illustrating overall survival in all patients enrolled in the study. B. Overall survivals of all patients enrolled in the study as a function of response to chemotherapy.
See this image and copyright information in PMC

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