First Phase II Results of Cisplatin/Epinephrine in Primary Liver Cancer

The interim results of an ongoing phase II trial of IntraDose (cisplatin [Platinol]/epinephrine) were presented at the 17th Annual Chemotherapy Foundation Symposium in New York City. Of 29 evaluable patients with liver cancer, 12 (41%) responded to treatment. Of the 12 responders, 6 achieved a complete response (100% reduction in viable tumor volume), while the other 6 showed a more than 50% reduction in viable tumor. To date, 10 of the 12 responders remain in remission, while the 2 other patients maintained remissions for 200+ days. Median survival time from the date of diagnosis for all patients has not yet been reached and is currently in excess of 15 months.

Centers from the United States, Europe, and Hong Kong are involved in the worldwide, open-label study. Participating American study centers are the Mayo Clinic, Johns Hopkins University, Northwestern University, Louisiana State University Medical Center, and St. Vincent’s Medical Center (Staten Island, New York). Philip Johnson, MD, professor and chairman, Department of Clinical Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, the leading enrollment center in the study, presented the study’s interim results.

Comparison With Other Therapies

In addition to the interim phase II results, Dr. Johnson also presented a comparison of patients treated with cisplatin/epinephrine to a cohort of contemporaneous patients receiving other therapies at leading medical centers in the United States and Hong Kong. The comparative patient data were developed by analyzing the medical records of patients who were similar to the patients treated in the cisplatin/epinephrine phase II protocol in terms of the number and size of their tumors, total tumor volume, and ineligibility for surgery. The comparison suggests that even at this stage of follow-up, there is a survival advantage for patients treated with cisplatin/epinephrine, although both a longer follow-up period and additional patients will need to be studied to provide conclusive evidence of a survival benefit.

“Data to date indicate that IntraDose is having a significant effect in producing clinical remissions and is showing an encouraging trend toward improved survival,” said Dr. Johnson. “IntraDose is a unique approach that may be a valid treatment option for many patients with localized liver tumors that are not amenable to surgical resection.”

At present, either surgical removal of the tumor or liver transplantation offers the only hope for long-term survival. However, only about 15% to 20% of patients are appropriate candidates for these procedures, said Adrian Di Bisceglie, MD, medical director, American Liver Foundation (ALF).

Drug Combination Injected Directly Into the Tumor Site

IntraDose is a collagen-containing gel that combines cisplatin and epinephrine. It is injected directly into the tumor site instead of intravenously, with the result that higher concentrations of the drug are targeted at the cancerous cells and there is less exposure of healthy tissues to the drug. The most frequently observed side effects in this trial to date are fever, local pain, weakness, nausea, vomiting, and loss of appetite. Infrequently, the treatment has resulted in bleeding from the tumor or worsening liver function.

The study is enrolling patients with biopsy-proven, inoperable hepatocellular carcinoma. Patients must have three or fewer tumors, with each not exceeding 7 cm in diameter, and no more than 200 cm3 in total tumor volume. Patients must also have adequate liver function. Patient responses are assessed using imaging techniques to measure the extent of tumor necrosis.

It should be emphasized that the complete results of this phase II study and the results of any future studies in primary liver cancer may not confirm the interim results described in this report.