Hepatic arterial infusion (HAI) and systemic chemotherapy for unresectable liver metastases (LM) from colorectal carcinoma (CC)

Median survival of untreated patients with LM from CC ranges from 3 to 12 months (m) after diagnosis. Better results were seen with HAI, also in association with systemic chemotherapy (JNCI; 88:252-8 1996). We treated 26 patients (20 men, 6 women; mean age 58 yr) with LM (18 synchronous and 8 metachronous; 20 pts had more than 3 lesions). Two different dose-schedules were administered: (1) 5-fluorouracil (5-FU) 200 mg/m2/day iv chronic continuous infusion (cci) and HAI with cyclophosphamide (CTX) 250 mg/m2 plus platin (P) 25 mg/m2 for 3 consecutive days every 3 weeks (10 pts); (2) 5-FU 300 mg/m2/day (cci) and CTX 330 mg/m2 plus P 33 mg/m2 with the same schedule as above (16 pts). 23 pts were chemo-naive, while 3 pts were pre-treated with 5 FU-based regimen. At a median follow up of 18 m, 18 pts were alive and 8 have died. Response (WHO criteria): on 22 evaluable pts (4 too early) 3 complete response (CR, 14%), 7 partial response (PR, 32%), 6 disease stabilization (SD, 27%) and 6 disease progression (PD, 27%) for an overall response rate of 46%. Median duration of response was 14 m (range 3 to 29+). The actuarial overall survival at 3 years was 35%. As regards the different chemotherapy dosages, better results were seen in patients who received the higher doses of drugs, with a response rate of 58% (vs 30%) and a median duration of response of 19 m (vs 11). Grade 3-4 toxicity (26 pts evaluable) was seen in 8 pts (31%), mostly hematological and mucosal, with one toxic death for severe enteritis. In conclusion, combined locoregional and systemic chemotherapy is active in unresectable LM from CC. The study is ongoing also with G-CSF rescue