OK-432与化疗剂联合腹腔用药治疗癌性腹水的疗效观察与机制探讨

The Efficacy and Mechanism of Intraperitoneal Combined Chemotherapy with OK-432for Malignant Ascites

目的:观察OK-432与MMC、5-FU联合腹腔给药治疗癌性腹水的疗效,并探讨这种联合用药的优势机理。方法:对34例腹腔恶性肿瘤合并癌性腹水患者采用MMC6mg/m2、5-FU0.5g/m2、OK-4325KE腹腔给药,1次/周,观察临床疗效与不良反应。测定了荷瘤小鼠腹水中细胞因子在OK-432腹腔给药前后的变化。结果:OK-432联合5-FU、MMC腹腔给药治疗癌性腹水的总有效率(CR+PR)为70.6%,其中CR为41.2%、PR为29.4%;患者的中位生存期为144天;腹水中癌细胞消失率为35.3%。主要不良反应有发热(6例体温超过38.5℃),粘连性肠梗阻(3例)。OK-432腹腔给药可使荷瘤小鼠腹水中IL-12、IFN-γ的浓度显著升高,IL-10的浓度显著降低(P<0.01)。结论:OK-432在腹腔内可诱导IL-12、IFN-γ的产生、抑制IL-10的分泌,从而增强化疗剂的疗效。与MMC、5-FU联合腹腔应用,能有效地控制恶性腹水,提高患者的生活质量,延长生存期。

Objective:To evaluate the efficacy of combined OK-432with chemotherapy in treatment of patients with malignant ascites and assess the potential mechanisms of the antitumor effect of chemotherapy enhanced by OK-432.Methods:Thirty-four patients with malignant ascites were treated intraperitoneally with MMC6mg /m 2 ,5-FU0.5g /m 2 ,OK-4325KE weekly.Using C3H mouse bearing MH134hepatoma (ascites model),the effect of OK -432on multicytokine production of ascites was investigated with ELISA.Results:The total effective rate(CR+PR)of OK-432plus MMC/5-FU on malignant ascites was70.6%(CR41.2%,PR29.4%)and the median survival time of patients was144days.Furthermore,cytologic examination revealed that tumor cells in the ascites disappeared in35.3%patients after treatment.The side-effect of the regimen included fever(>38.5℃in6cases),adhesive ileus(3cases),The analysis of cytokine kinetics revealed the level of IL-12and IFN-r were increased and IL-10decreased significantly(P<0.01)in the mouse ascites after OK -432administration intraperitoneally.Conclusion:For malignant ascites concomitant administration OK-432and MMC/5-FU could control the effusion effectively,improve the quality of life and prolong the survival time of the patients.The rationale of this regimen was that OK-432could improve the effect of chemotherapy through inducing IL-12/IFN-r production and inhibiting L-10secretion.