A phase II open-label multicenter trial of an injectable cisplatin-based gel preparation may improve treatment of primary liver cancer (hepatocellular carcinoma). Philip J. Johnson, MD, chairman, Department of Clinical Oncology,
NEW YORKA phase II open-label multicenter trial of an injectable cisplatin-based gel preparation may improve treatment of primary liver cancer (hepatocellular carcinoma). Philip J. Johnson, MD, chairman, Department of Clinical Oncology, Chinese University of Hong Kong, reported interim results of the trial at the Chemotherapy Foundation Symposium XVII.
Hepatocellular carcinoma is extremely common worldwide and highly malignant, representing more than 5% of all new cancers, Dr. Johnson said. Most cases result from chronic liver disease due to hepatitis B or C infection or alcohol-related damage. The number of new cases of hepatocellular carcinoma per year in the United States is estimated at 11,500 and is growing rapidly.
At present, surgical removal of the tumor or a liver transplant represent the only hope for cure. For as many as 80% of patients, however, the tumor is not resectable, and transplantation is not feasible. In the absence of effective alternative treatments, median survival is less than 1 year.
IntraDose Injectable Gel, being developed by Matrix Pharmaceuticals (Fremont, California), consists of the antitumor agent cisplatin (Platinol) and the vasoconstrictor epinephrine in a viscous, biodegradable gel made from bovine collagen. It is designed to deliver the drug directly to the tumor in a high-dose concentration and to keep it from entering the systemic circulation. Each milliliter of gel contains 4 mg of cisplatin and 0.1 mg of epinephrine.
The phase II study, being conducted at centers in the United States, Europe, and Hong Kong, has thus far enrolled 38 patients evaluable for safety and 29 for efficacy. Patients have unresectable hepatocellular carcinoma and have not received prior therapy. Response is measured by the degree of treatment-induced necrosis, viable tumor tissue volume, and tumor size using CT scans.
Up to 10 mL of the drug was delivered once weekly for 4 weeks by ultrasound- or CT-guided percutaneous intratumoral injection; 20 patients received one cycle; 8 received a second cycle of the drug.
Dr. Johnson said that an objective response was seen in 12 patients: six showed a complete response and six others a partial response. Nine patients had stable disease, and six had disease progression.
Of the 12 responders, 10 remained in remission at the time of the report, while the other two maintained remissions for more than 200 days. Median survival from the date of diagnosis for all patients is currently 15 months.
The gel injections were generally well tolerated, Dr. Johnson said. Effects related to the injection included hypertension, mild-to-moderate pain at the time of injection, and local pain at the treatment site following the injection.
Asthenia, vomiting, and nausea associated with cisplatin were also seen, although Dr. Johnson termed these toxicities mild. There was one treatment-related death due to spontaneous rupture of the tumor.
Although these results are preliminary, this vehicle for percutaneous administration of cisplatin may in future have an impact on survival of this devastating disease, Dr. Johnson said.