Ira Kline

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

Mice with early or advanced leukemia L1210 were treated with the inorganic antitumor agent, cis -platinum(II) diamminodichloride [ cis -Pt(II)], alone or combined wi

Evaluation of chemical agents against the plasma cell tumor LPC-1 in mice

Abstract Utilizing the advanced stage of an ascitic plasma cell tumor LPC-1 in mice, thirty-one drugs, plus cyclophosphamide employed as a positive standard, were tested for their ability to prolong the survival time of the animals. A determination was also made of the effect of the drugs on the biochemical parameter, abnormal protein production. Four drugs had an effect on both of these indices, i.e. tryptophan mustard (NSC-62403), aniline mustard (NSC-18429), cyclophosphamide (NSC-26271) and 5-fluorouracil (NSC-19893). Two of these, tryptophan mustard and cyclophosphamide, have been shown to be active clinically against plasma cell tumors. Nine additional compounds caused a significant increase in survival time but did not cause the abnormal protein to disappear. The current study indicates that the LPC-1 tumor offers a suitable test system for screening compounds for clinical trial against myeloma. A comparison is also made of the relative activities of the compounds in the L1210 leukemia, Walker 256 carcinosarcoma (IM) and LPC-1 systems in relation to clinical experience.

Enhanced response of leukemic (L1210) mice to combination chemotherapy with 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide (NSC-45388) and 5-fluorouracil (NSC-19893)

Clinical interest in 5‐fluorouracil prompted investigation of the therapeutic benefits of combination treatment with 5‐(3,3‐dimethyl‐1‐triazeno) imidazole‐4‐carboxamide (DIC). Daily combination treatment was superior to DIC or 5‐FU alone in BDF1 mice with early leukemia L1210. The maximum increase in life‐span elicited by this combination was 50 to 155% greater than that produced by 5‐FU alone. Against advanced L1210, the efficacy of DIC alone was diminished and the efficacy of 5‐FU was retained, but combination therapy was only 30% more effective than treatment with 5‐FU. Single drug therapy was comparable in DBA/2 and BDF1 mice, but combination treatment was more effective in BDF1 mice. The most effective daily combination generally utilized the optimal 5‐FU dose and relatively ineffective DIC doses. Apparently, the addition of relatively low doses of DIC to an optimal dose of 5‐FU contributed to effective treatment of the disease without, at the same time, increasing toxicity to the host.