Trials of 9-amino-20(S)-camptothecin in Boston

Joseph P. Eder, Eric Rubin, Richard Stone, Margaret Bryant, Guanxian Xu, Jeffrey Supko, Nancy Kinchla, Thomas Lynch, Selwyn Hurwitz, Dee Rodriguez, Charles Shapiro, Deborah Toppmeyer, Michael Grossbard, Evan Vosburg, Mark Huberman, Lowell Schnipper, Lawrence Shulman, Donald W. Kufe

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11 Scopus citations

Abstract

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 languageEnglish (US)
Pages (from-to)247-255
Number of pages9
JournalAnnals of the New York Academy of Sciences
Volume803
DOIs
StatePublished - Jan 1 1996

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Eder, J. P., Rubin, E., Stone, R., Bryant, M., Xu, G., Supko, J., Kinchla, N., Lynch, T., Hurwitz, S., Rodriguez, D., Shapiro, C., Toppmeyer, D., Grossbard, M., Vosburg, E., Huberman, M., Schnipper, L., Shulman, L., & Kufe, D. W. (1996). Trials of 9-amino-20(S)-camptothecin in Boston. Annals of the New York Academy of Sciences, 803, 247-255. https://doi.org/10.1111/j.1749-6632.1996.tb26394.x