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.
Vincents 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 studys
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.