Dr. Gary j. Becker young investigator award: intraarterial adenovirus for metastatic gastrointestinal cancer: activity, radiographic response, and survival.

摘要

PURPOSE: To determine the antitumoral activity and radiographic response pattern of intraarterial administration of a selective replication-competent adenovirus in patients with hepatic metastases from gastrointestinal carcinomas. MATERIALS AND METHODS: Thirty-five patients were treated, seven in the dose-escalation phase and 28 at high doses. Inclusion criteria allowed mild laboratory value and performance status abnormalities and as much as 50% replacement of hepatic volume by tumor. An attenuated adenovirus that selectively replicates in p53-deficient cells (Onyx-015) was administered by hepatic arterial infusion at doses as high as 2 x 10(12) particles for two cycles. Subsequent cycles (maximum of eight total) were administered in combination with intravenous 5-fluorouracil (5-FU) and leucovorin. RESULTS: Tumor responses were demonstrated in combination with chemotherapy, even in 5-FU-resistant patients. The 15 patients who responded radiographically showed a pattern of acute tumor enlargement despite normalization of laboratory and clinical parameters, followed by very slow regression of tumor size. Radiographic response did not correlate with p53 status. Median survival of radiographic responders (475 days) was significantly longer than that of nonresponders (143 days). CONCLUSIONS: Hepatic arterial infusion of the replication-selective adenovirus Onyx-015 in combination with chemotherapy resulted in tumor regressions in select patients, including some in whom previous chemotherapy had failed. A biphasic radiographic response pattern was demonstrated. The mechanism of action appears to be more complex than that seen in vitro.