Neoadjuvant Treatment with Weekly High-Dose 5-Fluorouracil as 24-Hour Infusion, Folinic Acid and Oxaliplatin in Patients with Primary Resectable Liver Metastases of Colorectal Cancer

Abstract

Purpose: To evaluate the efficacy and safety of neoadjuvant treatment comprising weekly high-dose 5-fluorouracil (5-FU) as a 24-hour infusion, folinic acid (FA) and biweekly oxaliplatin (L-OHP), followed by metastatic resection in patients with primarily resectable liver metastases of colorectal cancer (CRC). Patients and Methods: 20 patients with primarily resectable liver metastases of CRC were enrolled in a prospective phase II study. On an outpatient basis, the patients received a treatment regimen comprising biweekly 85 mg/m² L-OHP in the form of a 2-hour intravenous infusion and 500 mg/m² FA as a 1- to 2-hour intravenous infusion, followed by 2,600 mg/m² 5-FU administered as a 24-hour intravenous infusion once weekly. A single treatment cycle comprised one infusion per week during a period of 6 weeks followed by a 2-week rest. Two cycles were administered, with a third being added when the treatment was well tolerated. Thereafter, curative resection of the liver metastases was attempted, and the patients were followed up. Results: After neoadjuvant therapy, 2 of the original 20 patients showed complete remission (CR; 10%) and 18 patients partial remission (PR; 90%). As the main symptom of toxicity, diarrhea (CTC toxicity grade 3–4) was observed in 6 patients (30%), followed by vomiting in 3 patients (15%). The curative resectability rate was 80% (16 of 20). In 9 of 18 patients (50%) undergoing surgical intervention, mild postoperative complications, mainly wound healing disturbances (n = 5), occurred. No postoperative mortality was observed. Over a median follow-up of 23 months (12–38) 6 of 16 curatively resected patients developed distant metastases and 1 patient a local pelvic recurrence. The 2-year disease-free survival rate was 52% and the 2-year cancer-related survival rate 80%. Conclusion: The neoadjuvant treatment with weekly high-dose 5-FU in the form of a 24-hour infusion combined with FA and L-OHP is very effective and well tolerated. Surgical morbidity does not appear to be increased by the neoadjuvant treatment.

Role of systemic chemotherapy in the management of resected or resectable colorectal liver metastases: a systematic review and meta-analysis of randomized controlled trials

“…1). Eight studies were adjuvant or neoadjuvant phase II-III trials (42)(43)(44)(45)(46)(47)(48)(49). These studies did not allow the evaluation of combinatory effects of surgery with chemotherapy, but they were useful to understand the toxicity and long-term effects.…”

“…It is clear that after two years of treatment a high percentage of patients (about 50%) is free for relapse. Toxicities reported in studies were of low-moderate degree (42)(43)(44)(45)(46)(47)(48)(49). Serious toxicities were typical of chemotherapy (diarrhea, emesis, thrombocytopenia and neutropenia); no toxic deaths were reported.…”

Colorectal liver metastases contract centripetally with a response to chemotherapy

“…10,12 Recently, some investigators have administered preoperative chemotherapy to patients who have resectable liver metastases. [17][18][19] The rationale for this approach is that preoperative chemotherapy enables better selection of patients for resection and subsequent courses of chemotherapy. That is, responsiveness to preoperative chemotherapy may identify individuals who are more likely to benefit from postoperative chemotherapy.…”

Serum markers of matrix turnover as predictors for the evolution of colorectal cancer metastasis under chemotherapy

“…One cycle comprised six weekly infusions followed by 2 weeks of rest. A total of 16 patients received additional biweekly oxaliplatin (85 mg m À2 ) and three patients additional weekly irinotecan (80 mg m À2 ) (Wein et al, , 2003. Treatment response was monitored every 8 weeks by spiral CT and antitumour activity was evaluated in accordance with WHO criteria.…”

“…In all 37 patients, we recorded 112 episodes of tumour control, and in 16 of 37 patients we recorded episodes of tumour progression. The patients had been treated within the framework of two clinical phase II studies after obtaining approval by the local ethics committee (Wein et al, , 2003.…”