Trials of 9-amino-20(S)-camptothecin in Boston
| Autor: | Nancy M. Kinchla, Michael L. Grossbard, Guanxian Xu, Selwyn J. Hurwitz, Charles L. Shapiro, Richard Stone, Evan Vosburg, Jeffrey G. Supko, Mark S. Huberman, Deborah Toppmeyer, Eric J. Rubin, Lowell E. Schnipper, Dee Rodriguez, Margaret Bryant, Joseph Paul Eder, Donald Kufe, Lawrence N. Shulman, Thomas J. Lynch |
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| Rok vydání: | 1996 |
| Předmět: |
Adult
Male Antineoplastic Agents Breast Neoplasms Pharmacology Neutropenia General Biochemistry Genetics and Molecular Biology History and Philosophy of Science Refractory Pharmacokinetics Neoplasms medicine Humans Stomatitis Leukemia business.industry General Neuroscience Middle Aged medicine.disease Metastatic breast cancer Clinical trial DNA Topoisomerases Type I Camptothecin Female business medicine.drug Boston |
| Zdroj: | Annals of the New York Academy of Sciences. 803 |
| ISSN: | 0077-8923 |
| Popis: | 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 micrograms/M2/h at three week intervals. The Maximum Tolerated Dose (MTD) was 45 micrograms/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 micrograms/M2/h as a 72-hour continuous infusion. Evidence of antineoplastic activity has also been demonstrated. |
| Databáze: | OpenAIRE |
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