Influence of scheduling on therapeutic and toxic effect of AMSA in Lewis lung carcinoma

Abstract

The antitumor activity and toxic effect of AMSA were studied in Lewis lung carcinoma (3LL) at various stages of growth. The total dose of drug injected IP was 15 mg/kg, which is equivalent to the LD10. Different administration schedules were tested, these being single-injection schedules (day 1, 7, or 10 after tumor implantation) and repeated low-dose-injection regimens (days 1, 4, and 7 and days 1-7 after tumor implantation). Tumor weight inhibition, retardation of growth, reduction in the number of metastases, and median survival time of treated mice over controls were analyzed as end-points to evaluate the antitumor activity of AMSA. Early deaths and changes in white blood cell count were considered as parameters of toxicity. Our findings can be summarized as follows: (1) AMSA is only minimally effective against primary 3LL tumor at all the growth stages examined and no schedule-dependency is detected; (2) a greater reduction in metastases (70%-77%) is found when the drug is administered fractionally than when it is given in a single dose (39%-60%); (3) irreversible leukopenia is induced by the single-dose schedule of AMSA administration while after repeated low doses the white blood cell counts are in the same range of those of the control groups. Therefore, because of the schedule-dependency of toxicity and reduction in metastases, fractionated administration of AMSA at this dose level would be suitable for adjuvant chemotherapy.