Downstaging of hepatocellular carcinoma and liver metastases from colorectal cancer by selective intra-arterial chemotherapy.
BACKGROUND
Although resection is the sole chance of cure in patients with hepatocellular carcinoma (HCC) or metastatic colorectal cancer to the liver, most patients are not candidates for surgery at the time of diagnosis. Strategies aiming at downstaging large or multifocal tumors to enable curative resection are appealing. The aim of this study was to evaluate the effects of neoadjuvant selective intra-arterial chemotherapy in noncirrhotic patients with unresectable HCC or metastatic colorectal cancer to the liver in the absence of extrahepatic disease.


METHODS
Selective chemotherapy was provided by using a subcutaneous pump device via a catheter placed in the gastroduodenal artery. Chemotherapy regimen included floxuridine (0.2 mg/kg/day for 14 days) in each patient with additional boluses of cisplatin and doxorubicin on day 1 of each cycle in the presence of HCC. Patients were evaluated at 3, 6, 9, and 12 months for possible curative resection. Complete follow-up was available for each patient.


RESULTS
Twenty-eight patients with unresectable liver tumors (5 HCC and 23 metastatic colorectal cancer) were included in this study. There were no surgical complications related to pump insertion, and local chemotherapy was started within 1 week of surgery in each patient. The median follow-up in survivors was 31 months (range, 30 months to 5 years). Chemotherapy was well tolerated in 18 (64%) patients. Chemotherapy was discontinued in 4 patients because of abnormal liver function test results, and 2 of them required a biliary stent to relieve a biliary stricture. In 9 patients downstaging enabled curative resection (3 HCC, 6 colorectal metastasis). Seven of these patients were alive and tumor free at the completion of the study, with at least 2 years of follow-up. The actuarial survival rates at 3 years for HCC and colorectal metastases were 60% and 50%, respectively.


CONCLUSIONS
About one third of patients with unresectable liver tumors can be successfully treated by neoadjuvant intra-arterial chemotherapy followed by curative resection. This strategy appears particularly promising in patients with large HCC. This approach should be investigated further.
Clavien
Pierre-Alain
PA
Department of Surgery, Division of Hematology and Oncology, Duke University Medical Center, Durham, NC, USA.
Selzner
Nazia
N
Morse
Michael
M
Selzner
Markus
M
Paulson
Eric
E
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000473:pathology* / Q000556:secondary* / Q000601:surgery; D002945:Cisplatin / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000473:pathology*; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage; D006801:Humans; D007260:Infusion Pumps; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology* / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D014057:Tomography, X-Ray Computed
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D005467:Floxuridine; D004317:Doxorubicin; D002945:Cisplatin