WASHINGTON, DCIrinotecan (Camptosar) and epirubicin (Ellence) both have
single-agent activity in a number of cancers, and they have different toxicity
profiles. John L. Marshall, MD, and colleagues at the Lombardi Cancer Center in
Washington, DC, have been working on a phase I trial of epirubicin in
combination with irinotecan in patients with various advanced cancers. Dr.
Marshall, associate professor and director of Developmental Therapeutics and GI
Oncology at the Lombardi Cancer Center reported that doses had to be lowered
after the original protocol produced serious myelosuppression in the first four
patients treated, but the study has recently reopened.
Irinotecan and epirubicin are given on day 1 and on day 8 every 28 days.
Patients are evaluated every 8 weeks for response.
Due to concerns about myelosuppression, the starting irinotecan dose was 100
mg/m², which was about half of the recommended phase II dose. Epirubicin was
initially given at 40 mg/m².
"We thought we were in good shape with those starting doses. We were
wrong," Dr. Marshall said.
Questioning the Schedule
Two of the first four patients had grade 3/4 febrile neutropenia or
thrombocytopenia. One patient had a minor response to treatment. Due to the
high level of myelosuppression, the protocol has been altered to begin with
irinotecan at 50 mg/m² and epirubicin at 20 mg/m².
"There was evidence of activity in the biliary tree, and we think it
would be interesting to study this regimen in gastric gastroesophageal junction
cancers, but we need to question the schedule and think about other ways to
give this combination," Dr. Marshall said.