Rick, I am not sure 9-AC has been discussed much here, but, in any event, doing a search in medline for 9-AC and topoisomerase yields 11 references. A sample abstract with some clinical relevance follows:
Ann N Y Acad Sci 1996 Dec 13;803:247-255
Trials of 9-amino-20(S)-camptothecin in Boston.
Eder JP, 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 DW
Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
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. |
