Intracavitary therapy of murine ovarian cancer with cis-diamminedichloro-platinum(II) and 10-ethyl-10-deazaaminopterin incorporating systemic leucovorin protection Journal Article
| Authors: | Sirotnak, F. M.; Schmid, F. A.; DeGraw, J. I. |
| Article Title: | Intracavitary therapy of murine ovarian cancer with cis-diamminedichloro-platinum(II) and 10-ethyl-10-deazaaminopterin incorporating systemic leucovorin protection |
| Abstract: | Administration i.p. of 10-ethyl-10-deazaaminopterin (10EDAM) with cis-diamminedichloroplatinum(II) (cis-Pt) had significant antitumor activity against the murine ovarian tumor. This tumor is a teratoma originating in the ovary with pathogenesis and metastatic properties similar to those of human ovarian cancer. Drug was given on a schedule of once every 3 days for 3 doses 1 or 2 days after i.p. implant of 107 tumor cells. Despite the 2-fold attenuation of dosage required, antitumor activity of the combination (increased life span, 161%) was approximately twice that obtained with maximum tolerated doses of either agent alone and tumor-free, long-term survivors were obtained. Incorporation of s.c. calcium leucovorin administration 16 h after each dose of 10EDAM and cis-Pt allowed a 4-fold increase in dosage of 10-EDAM without an increase in toxicity, increased median survival by an additional 120%, and quadrupled the number of tumor-free, long-term survivors to 40% of treated animals. By comparison, methotrexate was only modestly active against this tumor model either as a single agent, with cis-Pt, or with delayed s.c. calcium leucovorin administration. These results appear to suggest that 10EDAM with cis-Pt may have considerable potential for intracavitary therapy of human cancer, including ovarian carcinoma, particularly when incorporating delayed systemic calcium leucovorin administration. © 1989, American Association for Cancer Research. All rights reserved. |
| Keywords: | cisplatin; nonhuman; comparative study; methotrexate; ovarian neoplasms; animal cell; mouse; animal; mice; ovary cancer; animal experiment; drug evaluation, preclinical; folinic acid; folic acid antagonists; injections, subcutaneous; leucovorin; aminopterin; mice, inbred c3h; intraperitoneal drug administration; injections, intraperitoneal; edatrexate; male; female; priority journal; support, non-u.s. gov't; support, u.s. gov't, p.h.s. |
| Journal Title: | Cancer Research |
| Volume: | 49 |
| Issue: | 11 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1989-06-01 |
| Start Page: | 2890 |
| End Page: | 2893 |
| Language: | English |
| PUBMED: | 2785847 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 14 April 2020 -- Source: Scopus |
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