Source: Brachytherapy  |  Posted 7 years ago

By Chris Berrie

PARIS, FRANCE -- February 3, 2005 -- The use of intra-arterial locoregional therapy, or hepatic artery infusion (HAI) of a combination of folinic acid (FA), 5-fluorouracil (5FU) and oxaliplatin is safe and highly effective, and has high remission and long survival rates for patients with colorectal cancer metastases exclusive to the liver.

This three-institute, phase 2 study was presented here February 1[^]st[] at the 16[^]th[] International Conference on Anti-Cancer Treatment along with the final analysis of three HAI dose-finding studies by Dr. Katrin Eichler, MD, Assistant Radiologist, Institute for Diagnostic and Interventional Radiology, J.W. Goethe-University, Frankfurt, Germany.

The treatment options for regional therapy of liver malignancies include a number of local ablative procedures and local vascular procedures. As a rationale for their use of the latter, Dr. Eichler said, "We know that 75% of the normal liver parenchyma is supplied by the portal vein and only 25% by the hepatic artery, while on the other hand, hepatic malignancies normally have a high number of supplying arterial blood vessels drawing blood from the hepatic artery." This thus suggested that intra-arterial chemoperfusion and chemoembolisation could be used for tumour downsizing and devascularisation with palliative and even neoadjuvant intentions, she said.

The 24 patients enrolled (median age 62 years; range, 34-77 years) had colorectal cancers (colon, 67%) with metastases exclusive to the liver. Fifty-eight percent were chemonaive, with the rest not having received any alternative chemotherapy in the preceding 6 months.

The dose regimen was based directly on the results of a prior phase 1 study and included intra-arterial infusion of folinic acid 200 mg/m[^]2[] over 1 hour and 5-FU 600 mg/m[^]2[] over 2 hours on days 1 to 5 inclusive. To this was added oxaliplatin 62.5 mg/m[^]2[] over 4 hours on days 2 and 4. This cycle was then repeated every 4 weeks.

After a median of seven cycles (range, 2-26) per patient, the overall response rate was 70.8%, the complete response rate was 20.8%, and partial response was 50.0%, while median survival was 24.6 months. When the overall survival was considered as a function of cycles per patient, there was a survival increase of 22.2 to 27.4 months from six cycles (n = 9) to nine cycles (n = 13), respectively.

The median time to progression was 12.9 months, with a long-term survival rate after 4 years of 20.8%. This included the partial liver resection and radiofrequency ablation that were each used twice to treat four of these patients after they had achieved remission through HAI chemotherapy.

The toxicity profile showed that nausea and vomiting, anaemia, and pain in the upper abdomen were each experienced by 75% of patients, although the World Health Organisation grade 3-4 toxicities were lower -- leukopenia (19%), thrombocytopenia (10%), hyperbilirubinemia (10%), abdominal pain (10%) and diarrhoea (5%).

Intra-arterial locoregional application of this three-agent regimen is a highly effective treatment with long survival rates in patients with colorectal cancer with metastases limited exclusively to the liver, the researchers concluded. From the results of the associated trials reported, these approaches should also be further promoted by the combination of HAI chemotherapy with starch microspheres as a chemoembolisation, Dr. Eichler said.

[Study Title: High Efficacy of Hepatic Artery Infusion Chemoembolisation of Folinic Acid 5-Fluorouracil (FA/FU) Plus Oxaliplatin, Gemcitabine and Peg. Lip. Doxorubicin in Patients With Liver Cancer.]