A phase 1 trial of flavopiridol combined with 5-fluorouracil (5-FU) and leucovorin (CF) in patients with advanced malignancies Year: 2003 Abstract No: 872 Category: Other Novel Agents Author(s): K. C. Bible, J. L. Lensing, S. A. Nelson, P. J. Atherton, J. A. Sloan, C. Erlichman; Mayo Clinic, Rochester, MN Abstract: Flavopiridol, a potent CDK inhibitor and DNA binding agent, was combined with 5-FU and CF to establish MTD and toxicities in patients with advanced solid tumors. Flavopiridol was increased in a stepwise fashion (cohorts of 3 patients) from 40 to 100 mg/m2/24 h (day 1), while 5-FU was fixed at 350 mg/m2/d (1 hour IV infusion) and CF at 20 mg/m2/day (both, days 2-5). 24 patients were enrolled, with 68 cycles of chemotherapy administered. 11 of 24 enrolled patients had colorectal cancers and the median number of prior chemotherapy regimens was 2. Mean age was 58 years and 58% of enrolled patients were male. Mean time on study was 1.5 months. Flavopiridol was escalated to 100 mg/m2 without appreciable dose-limiting toxicity. Non-dose-limiting toxicities were diarrhea (18%), fatigue (13%), nausea (12%), anorexia (10%), anemia (4%), vomiting (3%), tumor pain (3%), dehydration (2%), hypokalemia (1%) and hypoglycemia (1%). Leukopenia or thrombocytopenia occurred in only 3% and 7% of patients respectively. Grade 3 toxicities were diarrhea (13%); headache, fatigue, hypotension, syncope, vasovagal episode and dehydration (4% each). One patient with colon cancer metastatic to liver who had previously failed 5-FU-based therapy attained a partial response, while stable disease lasting >3 months was seen in 13% of the remaining patients. We conclude that flavopiridol, 5-FU and CF can be safely combined in the treatment of cancer patients and propose Phase 2 dosages of 100 mg/m2/24 h flavopiridol (day 1 only), 350 mg.m2/d 5-FU and CF 20 mg/m2/day (both, days 2-5). Plans are currently underway to add CPT-11 to this combination. Supported by CA15083 and CA66912. Abstract 932 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.