Annals of Oncology 14:856-863, 2003
© 2003 European Society for Medical Oncology
Original Paper |
Hepatic arterial infusion using pirarubicin combined with systemic chemotherapy: a phase II study in patients with nonresectable liver metastases from colorectal cancer
1 Institut Gustave Roussy, Villejuif; 2 Institut Val d’Aurelle, Montpellier; 3 Centre François Baclesse, Caen; 4 Clinique Courlancy, Reims; 5 Centre Paoli Calmette, Marseilles; 6 Hopital Croix Rousse, Lyon; 7 Centre Oscar Lambret, Lille; 8 Centre René Gauducheau, Saint Herblain; 9 CHR Bordeaux, Pessac; 10 Laboratoire Aventis France, Paris; 11 Hopital Ambroise Paré, Boulogne, France
Received 5 November 2002; revised 16 December 2002; accepted 27 January 2003
Background:
A prospective phase II study was performed to determine the feasibility, efficacy and safety of arterial hepatic infusion (HAI) using pirarubicin combined with intravenous chemotherapy.
Patients and methods:
From December 1991 to April 1994, 75 patients with unresectable colorectal metastases confined to the liver were included in this multicenter study to receive intra-arterial hepatic pirarubicin and a systemic monthly regimen of 5-fluorouracil (5-FU) and folinic acid. Sixty-four patients were analyzed in the intention-to-treat analysis and 61 in the per-protocol analysis.
Results:
Tolerance of this regimen was rather good; however, functional catheter problems were observed in 29 patients (45%) resulting in failure of HAI in 21 cases (33%) after a median of three cycles; vomiting grade 3 was present in 12.5% of patients, neutropenia grade 4 in 23% and alopecia grade 3 in 19%. The overall response rate was 31.9% in intention-to-treat analysis, and 39.3% in per-protocol analysis. Extrahepatic progression was reported in only 21.7% of patients. Time to hepatic progression and extra-hepatic progression was 8.3 and 15 months, respectively, in intention-to-treat analysis, and 11 and 18 months, respectively, in per-protocol analysis. Median survival was 19 and 20 months in intention-to-treat analysis and per-protocol, respectively.
Conclusions:
In our study, the combination of intra-arterial pirarubicin and intravenous chemotherapy demonstrated some efficacy and good tolerance in the treatment of isolated colorectal liver metastases. This treatment seems to prevent extra-hepatic spread and prolong survival time. The results of this study have to be confirmed by new trials using more active systemic chemotherapy.
Key words: colorectal cancer, hepatic arterial chemotherapy, liver metastases, pirarubicin