Taxol, dissolved in
cremophor/
ethanol (50/50), followed by further dilution with saline, was successfully administered intravenously (IV) to mice bearing subcutaneously (SC) implanted murine Madison 109 lung
carcinoma (M109), M5076
sarcoma, or seven different human
tumor xenografts, including A431 vulva; A2780 ovarian; LX-1, H2981, and L2987 lung; and RCA and HCT-116 colon
carcinomas.
Taxol was active in all these distal site
tumor models except the M5076
sarcoma. Schedule dependency and dose-response evaluations involving
Taxol were studied in the SC M109 model.
Taxol was given IV, and all treatments were of 7 days' duration. Each schedule was evaluated using several dose levels designed to incorporate the likely optimal (and maximum tolerated) dose(s). On the best schedule, daily
injections for 7 days,
Taxol exhibited a flat dose response; that is, good activity was obtained at
Taxol dose levels that were only a fraction of its maximum tolerated dose. This profile provided an advantageous opportunity to evaluate
Taxol-based
combination chemotherapy. In a format in which
Taxol was given every day on days 1 through 5, IV, and other drugs were given on days 1 and 5 (IV or intraperitoneally, IP) versus SC M109, dose titrations of each agent were evaluated singularly and in various
Taxol-based combinations. The combination of
Taxol plus
cisplatin yielded a delay in
tumor growth (17.8 days) that was minimally superior (P < .05) to the best delays caused by either
drug alone (e.g., 13.5 days for
Taxol); there was no enhancement of lifespan beyond that obtained using
Taxol alone.(ABSTRACT TRUNCATED AT 250 WORDS)