Intra-arterial hepatic chemotherapy with 5-fluorouracil and 5-methyltetrahydrofolate in the treatment of unresectable liver metastases from colorectal cancer.
Treatment of patients with hepatic metastases from colorectal cancer using hepatic artery fluorodeoxyuridine (FUDR) has been reported to induce high remission rates but also a high incidence of limiting hepatobiliary toxicity. In an attempt to obviate the limiting FUDR toxic effects, a phase I-II study was undertaken to establish the efficacy and tolerability of intra-hepatic 5-fluorouracil (5-FU) when given in combination with 5-methyltetrahydrofolate. Patients with colorectal liver metastases (n = 17) received escalating doses of 5-FU as a 1 h infusion with a fixed dose (100 mg/m2) of intra-hepatic 5-methyltetrahydrofolate (4 h infusion) once a week. Dose limiting toxicity was hepatic and gastrointestinal (diarrhea) and occurred at doses > or = 350 mg/m2 5-FU. Other adverse effects included nausea/vomiting and cutaneous toxicity. One patient achieved a complete response and 2 a partial response (mean duration = 9 months) while 11 had stable disease. Patients with complete or partial responses had a mean survival of 17 months, while patients with stable disease survived 13 months and those with disease progression 5.5 months on average. These results suggest that this is a well tolerated regimen although with efficacy at the lower level of the range observed with fluoropyrimidines.
II Divisione di Chirurgia Generale, Ospedale di Careggi, Firenze, Italy.
A
A
Valeri
E
E
Mini
P
P
Tonelli
F
F
Veneri
B
B
Neri
D
D
Borrelli
T
T
Mazzei
D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006499:Hepatic Artery; D006801:Humans; D015918:Infusion Pumps, Implantable; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D013763:Tetrahydrofolates / Q000008:administration & dosage*
D013763:Tetrahydrofolates; C005984:5-methyltetrahydrofolate; D005472:Fluorouracil