The antitumor activity of
ASTA Z 7557, a stabilized primary metabolite of
cyclophosphamide, was evaluated in comparison with
cyclophosphamide (CP) against different rodent
tumor systems. At equimolar doses, which corresponded in mg/kg to the optimal doses of each compound,
Z 7557 showed a higher therapeutic activity than CP when both drugs were administered intraperitoneally (ip) during 5 consecutive days. The
drug remained active against a P388 subline totally resistant to CP, but to a much lesser extent. The ip-implanted
B16 melanoma was highly sensitive to 100 and 50 mg/kg administered during 9 consecutive days: an increase in lifespan (ILS) of 244% was produced and 5 mice out of 10 were cured. This treatment administered against
Lewis lung carcinoma (LL) transplanted intravenously (iv) induced an ILS of 179% and 3 mice out of 10 survived on day 60. This effect was slightly inferior to that produced by 50 mg/kg of CP, but is balanced by the number of long-term survivors recorded after administration of low doses of
Z 7557. When mice bearing the subcutaneously (sc) implanted colon 38 (C38)
tumor were treated with 200 mg/kg on days 2 and 9, the
tumor growth was inhibited by 83% in comparison to the control mice. The wide range of activity of
Z 7557, its stability and its different chemical reactivity as compared to CP appear to justify interest in this activated oxazaphosphorine.