The Enhanced Therapeutic Effect of cis-Platinum (II) Diamminodichloride against L1210 Leukemia when Combined with Cyclophosphamide or 1,2-bis(3,5-Dioxopiperazine-1-yl)propane or Several other Antitumor Agents

Abstract

Mice with early or advanced leukemia L1210 were treated with the inorganic antitumor agent, cis-platinum(II) diamminodichloride [cis-Pt(II)], alone or combined with each of 13 other antileukemic drugs. Against early L1210 leukemia, combinations of cis-Pt(II) plus cyclophosphamide, isophosphamide, 1,2-bis(3,5-dioxopiperazine-1-yl)ρropane [ICRF-159] or emetine elicited increases in life-span at least double those achieved with the more effective of the individual drugs. Combinations of cis-Pt(II) plus 9 other antileukemic drugs showed some degree of therapeutic advantage over individual drug treatment. The combination of cis-Pt(II) plus urea, 1,3-bis(2-chloroethyl)-1-nitroso (BCNU) was not more effective than treatment with BCNU alone. Studies of the combination of cis-Pt(II) plus cyclophosphamide or ICRF-159 were extended to treatment of advanced L1210 leukemia and showed that the advantage of combination therapy over single-drug treatment was retained against systemic disease.