Fisher B, Wolmark N, Rubin H, Saffer E
J Natl Cancer Inst. 1975 Nov;55(5):1147-53. doi: 10.1093/jnci/55.5.1147.
Studies from this laboratory have indicated that the administration of cyclophosphamide (CY) and Corynebacterium parvum (CP) over a prolonged time to C3H mice with established measurable tumors resulted in complete arrest of tumor growth as well as partial and complete regressions in many instances. The present investigations on optimal dosage, route, frequency, and sequence of administration of CY and CP in the model system were performed to obtain information that could be useful in the design of chemotherapeutic and immunotherapeutic regimens for the treatment of human tumors. Findings have suggested the need for administration of CP in more than one instance. Although a single dose of CP in combination with weekly injections of CY had a significantly prolonged inhibitory effect, weekly doses of CP and CY were more effective. We also concluded that the time between doses of an immunostimulating agent (I-I interval) as well as between administration of chemotherapy (C-C interval) may be critical for an optimal result. In this model system, C-C and I-I intervals of 7 days inhibited tumor growth most effectively. The time between administration of chemotherapy and immunotherapy (C-I interval) has been considered critical. Whereas slightly better results were achieved in these studies when the immunotherapy was administered 4 days after the CY or when the C-I interval was +4 days, almost equally good results were obtained when both agents were given on the same day, which signified that the C-I interval may not be as critical as other investigators have reported. The present findings confirmed and extended our prior observations and indicated that the iv and ip routes of administration were superior to the im and sc routes in our model. The observed tumor growth inhibition was a result of both chemotherapeutic and immunotherapeutic modalities; also, the inhibitory properties of the regimen were more related to the chemotherapeutic component. Finally, almost identical tumor growth inhibition was observed when CP obtained from two different laboratories was used in conjunction with CY.
本实验室的研究表明，对患有可测量肿瘤的C3H小鼠长期给予环磷酰胺（CY）和短小棒状杆菌（CP），会导致肿瘤生长完全停滞，并且在许多情况下会出现部分或完全消退。在该模型系统中，对CY和CP的最佳剂量、给药途径、给药频率和给药顺序进行了当前研究，以获取有助于设计治疗人类肿瘤的化疗和免疫治疗方案的信息。研究结果表明需要多次给予CP。虽然单剂量CP与每周注射CY联合使用具有显著延长的抑制作用，但每周剂量的CP和CY更有效。我们还得出结论，免疫刺激剂给药间隔时间（I-I间隔）以及化疗给药间隔时间（C-C间隔）对于获得最佳结果可能至关重要。在该模型系统中，7天的C-C和I-I间隔最有效地抑制肿瘤生长。化疗和免疫治疗给药间隔时间（C-I间隔）被认为至关重要。虽然在这些研究中，当免疫治疗在CY给药后4天进行或C-I间隔为+4天时取得了稍好的结果，但当两种药物在同一天给药时也获得了几乎同样好的结果，这表明C-I间隔可能不像其他研究者报道的那样关键。当前研究结果证实并扩展了我们之前的观察结果，表明在我们的模型中，静脉注射和腹腔注射给药途径优于肌肉注射和皮下注射途径。观察到的肿瘤生长抑制是化疗和免疫治疗两种方式的结果；此外，该方案的抑制特性与化疗成分的关系更大。最后，当使用从两个不同实验室获得的CP与CY联合使用时，观察到几乎相同的肿瘤生长抑制效果。
