Phase II study on combined intravenous and intra-arterial chemotherapy with gemcitabine and mitomycin C in patients with advanced pancreatic cancer.

BACKGROUND/AIMS: This prospective phase II study on a combination of intraarterial (i.a.) and systemic chemotherapy was performed to test whether regional chemotherapy may overcome the chemoresistance of pancreatic cancer. METHODOLOGY: One treatment cycle consisted of an i.a. infusion through an angiographic catheter into the celiac artery of 8.5mg/m2 mitomycin C (MMC) and 500 mg/m2 gemcitabine on days 1 and 22, and intravenous infusions of 500 mg/m2 gemcitabine on days 8 and 15. Study-endpoints were overall survival and tumor response as measured by computed tomography (CT). Treatment was continued until disease progression or complete remission on CT. RESULTS: Thirty-seven treatment cycles were performed in 17 patients. The most frequent side effects were hematological with 18 episodes of grade III/IV toxicities. According to radiographic and tumor marker criteria, four (24%) and seven patients (41%), respectively, demonstrated an objective response. The median actual progression-free and overall survivals were 4.6 and 9.1 months, respectively. Patients without distant metastases had a longer median survival (15 months) than those with distant metastases (7.1 months, p = 0.037). CONCLUSIONS: This combination treatment was well tolerated and resulted in tumor response rates, median overall- and progression-free survival times superior to systemic gemcitabine chemotherapy, and comparable to the more toxic FOLFIRINOX regimen.

Prospective pilot study of neoadjuvant chemotherapy with 5-fluorouracil, folinic acid and oxaliplatin in resectable liver metastases of colorectal cancer. Analysis of 42 neoadjuvant chemotherapies.

PURPOSE: Since there are currently no data available from a prospective trial, the primary objective of this prospective study was to investigate whether the rate of R0-liver resections without morbidity would be at least 50 % in patients with neoadjuvant chemotherapy for colorectal liver metastases. PATIENTS AND METHODS: 42 patients were treated with a biweekly FOLFOX regimen. Chemotherapy consisted of a 2-hour infusion of folinic acid (FOL) 500 mg/m2, followed by a 24-hour infusion of 5- fluorouracil (F) 2000 mg/m2 daily for two days. Oxaliplatin (OX) 85 mg/m 2 was given simultaneously with FOL. Treatment allocation was randomized with either 3 or 6 cycles for the final 30 patients. A liver resection was performed 2 to 5 weeks after the final infusion. RESULTS: An objective response was observed in 20 of 42 patients (response rate was 27 % higher after 6 cycles). Liver resection (R0) could be performed in 34 patients. Postoperative complications were reported in 14 patients (13 occurring within 30 days after resection) and severe complications in 5 cases (including two deaths after extended resection). Liver failure and persistent biliary fistula were the most frequently documented complications. There was no relevant difference in safety criteria between 3 and 6 applications. CONCLUSION: The use of neoadjuvant chemotherapy in resectable liver metastases induced significant remissions without increasing morbidity. The rate of severe complications and cases of no R0-resection in this study was 31 % and was with that significantly lower than 50 % (95 % CI 17.6 %-47.1 %). The risk to the patient is therefore acceptable when undergoing neoadjuvant treatment in a prospective intergroup trial.

Technical complications of continuous intra-arterial chemotherapy with 5-fluorodeoxyuridine and 5-fluorouracil for colorectal liver metastases.

BACKGROUND: Intra-arterial chemotherapy is an effective modality to treat unresectable hepatic metastases from colorectal primaries if systemic chemotherapy has failed. Response rates of more than 40% and a median survival of 15 to 25 months have been reported from randomized trials. In this retrospective study, we analyzed specific technical complications associated with continuous intra-arterial chemotherapy for colorectal liver metastases. METHODS: From 1982 to 1995, single-center clinical data from 180 patients with colorectal liver metastases were evaluated. Continuous intra-arterial chemotherapy was administered using either an implanted infusion pump or an intra-arterial port with an external infusion pump. The intra-arterial catheter was implanted according to the Watkins' technique. The treatment protocols consisted of 5-fluorouracil- or 5-fluorodeoxyuridine-based regimens. RESULTS: A total of 70 patients (39%) received an intra-arterial infusion pump and 110 patients (61%) an intra-arterial port. Sixty-eight technical complications affected port systems (62%), whereas 29 patients with pumps (41%) were affected by technical complications. Therapy-relevant complications were observed in 47% of the ports and 30% of the infusion pumps. The median complication-free survival was 12.2 months for infusion pumps and 7.3 months for ports (P =.0016). CONCLUSIONS: Our data demonstrate that pumps are superior to ports in terms of complication rate and complication-free survival. On the basis of our results, pumps have a potential for a longer treatment, which may result in a prolonged median survival.