9-Amino-20(S)-camptothecin (9-AC) is an analog of camptothecin with limited water solubility which has shown significant preclinical activity in a variety of human solid tumor xenografts. A Phase I trial using a soluble formulation of 9-AC, given as a 72-hour continuous infusion, has been completed. Thirty-one patients with resistant cancers received 5-60 μg/M2/h at three week intervals. The Maximum Tolerated Dose (MTD) was 45 μg/M2/hour. Neutropenia was the dose limiting toxicity, with few significant non-myelosuppressive toxicities. Minor responses were seen in 3/31 patients. Pharmacokinetic studies of 9-AC lactone (closed ring) showed substantial interpatient variability with a predicted half-life of 36 hours. A phase I/II trial of the same formulation of 9-AC is ongoing in refractory leukemia. Stomatitis and diarrhea are the non-myelosuppressive dose limiting toxicities. Evidence of antineoplastic activity has been seen in 3/15 patients. A Phase II trial in previously untreated metastatic breast cancer is also underway. A Phase I trial of a colloidal dispersion formulation, not yet completed, is better tolerated with a MTD > 45 μg/M2/h as a 72-hour continuous infusion. Evidence of antineoplastic activity has also been demonstrated.
|Original language||English (US)|
|Number of pages||9|
|Journal||Annals of the New York Academy of Sciences|
|State||Published - 1996|
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- History and Philosophy of Science