A phase I study of the protein kinase C modulator bryostatain-1 and gemcitabine. Year: 2003 Abstract No: 930 Category: Other Novel Agents Author(s): D. Ibrahim, B. F. El-Rayes, S. M. Gadgeel, P. Lorusso, P. A. Philip; Karmanos Cancer Institute, Detroit, MI Abstract: Bryostatin-1 is a macrocyclic lactone with PKC inhibitory activity. Gemcitabine is a nucleotide analog with significant activity in breast, gastrointestinal, lung and ovarian cancer. In preclinical models, bryostatin-1 has been shown to enhance the activity of other anti-tumor agents including gemcitabine. The primary objective of this Phase I study was to determine the maximum tolerated dose (MTD) of bryostatin-1 and gemcitabine. Eligible patients were age 18 years or older, had histologic or cytologic diagnosis of non-hematologic cancer resistant to conventional treatment, life expectancy of more than 3 months, normal renal, hepatic and bone marrow function, and a SWOG performance status of 0 to 2. Gemcitabine was administered over 30 minutes and was followed by bryostatin-1 by continuous infusion over 24 hours on days 1, 8 and 15 of a 28-day cycle. Bryostatin-1 (mg/m2)/ gemcitabine (mg/m2) doses were escalated as follows: 25/600, 25/800, 25/1000, 30/1000, 35/1000, 45/1000, respectively. Twenty-seven patients (15 females, 12 males; mean age 54 years, range 18 ? 74 years) have been treated at 6 dose levels. The median number of treatment cycles was 2 (range 1-10) and a total of 63 cycles. Three patients developed dose limiting toxicities: myelosuppression, myalagia and elevation of SGPT. Eight grade 3 toxicities have been noticed (anemia 2, leucopoenia 3, thrombocytopenia 2, nausea 1). No treatment related mortality has been observed. 9 patients have stable disease. Two heavily pretreated patients with breast and colon cancer experienced partial response lasting 10+ months and 8+ months, respectively. MTD has not been defined. T he combination of bryostatin-1 and gemcitabine appears to be well tolerated with limited grade 3 toxicity. Supported by UO-1 grant CA 62487. 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.