Evaluation of single agents and combinations of chemotherapeutic agents in mouse colon carcinomas
Evaluation of single agents and combinations of chemotherapeutic agents in mouse colon carcinomas
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单药和联合化疗药物对小鼠结肠癌的疗效评价
作者：
Phd T. H. CORBETT;J. D. D. P. GRISWOLD;B. J. Roberts;Dvm J. C. PECKHAM;Phd F. M. Schabel;Gwendolyn Gamble;Tina Ayer;Billy Golden;John Maura;Patricia Blair;Michael Chambers;Joynetta Seay;Karren Weeks;C. Andrews;Delois Huntington;Rosa Griffin;Albert Moody
测试了单一药剂和药剂组合对小鼠中四种可移植结肠肿瘤的抗肿瘤活性。最令人印象深刻的抗肿瘤活性是使用胍和胍+ 5-FU联合治疗结肠腺癌No. 38。当以Q7 d时间表（两个实验）同时注射组合时，获得抗肿瘤增强作用，但不以交替给药时间表（两种药剂的注射间隔3或4天）注射。安古定仅在对5-FU非常敏感的结肠肿瘤中具有高度活性。高5-FU敏感性和高胍敏感性之间的相关性可能是巧合或可能具有预测价值。针对一种或多种结肠肿瘤的其它活性单一药剂和药剂组合包括5-FU、5-FUdR、MeCCNU、BCNU、高三尖杉酯碱、ara-C、顺式-Pt-II、二脱水卫矛醇、哌嗪二酮、环磷酰胺; MeCCNU + 5-FU;阿霉素+ 5-FU;阿霉素+环磷酰胺;阿霉素+ palmO-ara-C;环磷酰胺+丙卡巴肼;和5-FU + palmO-ara-C。(The 5-FU + palmO-ara-C的组合仅在交替时间表上增强。转移性结肠肿瘤的手术-化疗辅助治疗的结果表明，如果一种药物或组合对中度晚期肿瘤肿块具有高度活性，则该治疗在手术后对残留转移性疾病也具有高度活性。匡威亦然。也就是说，如果药剂或组合对中度晚期疾病无活性或仅有少量活性，则手术后对残余转移性疾病的治疗也相对无效。基于26号结肠肿瘤的手术辅助实验，有条件地推荐以下药物和组合：MeCCNU + 5-FU; MeCCNU + Ara-C;环磷酰胺+ Ara-C; BCNU+ 5-FU和MeCCNU。还假设那些对晚期疾病有活性的药物在手术后可能对残留的转移细胞有活性。因此，对晚期结肠腺癌38号具有高度活性的药物可能是辅助治疗的候选药物。在此基础上，推荐使用胍和胍+ 5-FU。
Single agents and combinations of agents were tested for antitumor activity against four transplantable colon tumors in mice. The most impressive anti‐tumor activity was obtained with anguidine and the combination of anguidine + 5‐FU against colon adenocarcinoma No. 38. Antitumor potentiation was obtained when the combination was injected simultaneously on a Q7d schedule (two experiments), but not on an alternating schedule of administration (3 or 4 days separating injections of the two agents). Anguidine was highly active only in a colon tumor that was very responsive to 5‐FU. The correlation between high 5‐FU sensitivity and high anguidine sensitivity may be coincidental or could be of predictive value. Other active single agents and combinations of agents against one or more of the colon tumors include 5‐FU, 5‐FUdR, MeCCNU, BCNU, homoharringtonine, ara‐C, Cis‐Pt‐II, dianhydrogalactitol, piperazinedione, cyclophosphamide; MeCCNU + 5‐FU; Adriamycin + 5‐FU; Adriamycin + cyclophosphamide; Adriamycin + palmO‐ara‐C; cyclophosphamide + procarbazine; and 5‐FU + palmO‐ara‐C. (The combination of 5‐FU + palmO‐ara‐C was potentiating only on an alternating schedule.) The results of surgery‐chemotherapy adjuvant treatment of metastatic colon tumors established that if an agent or a combination was highly active against moderately advanced tumor masses, this treatment was also highly active after surgery against residual metastatic disease. The converse was also true. That is, if the agent or combination was inactive or marginally active against moderately advanced disease, the treatment was also relatively ineffectual after surgery against residual metastatic disease. Based on surgical‐adjuvant experiments with colon tumor No. 26, the following agents and combinations are conditionally recommended: MeCCNU + 5‐FU; MeCCNU + Ara‐C; cyclophosphamide + Ara‐C; BCNU+ 5‐FU and MeCCNU. It is also assumed that those agents active against the advanced disease are likely to be active after surgery against residual metastatic cells. Thus, agents highly active against advanced‐stage colon adenocarcinoma No. 38 are possible candidates for adjuvant therapy. On this basis, anguidine and anguidine + 5‐FU are recommended.