The Experimental Study And Clinical Observation Of Lobaplatin In The Intraperitoneal Treatment Of Gastrointestinal Cancer

Currently, surgery is still preferred treatment for gastrointestinal cancer. But for the advanced patients, especially for whose serous membrane was infiltrated, recurrent or metastasis rate is still very high. The common recurrent sites are excised site, surface of liver and peritoneum. The therapeutic effect of introvenous chemotherapy alone is not satisfactory for the patients whose ascites test or peritoneum metastastasis is positve or for patients with refractory ascite. Intraperitoneal chemotherapy has obvious advantages under these circumstances. For it could provide high local drug concentration, low toxicity, and direct interaction. So it is widely used in clinical practice. Cisplatin, carboplatin, oxaliplatin are commonly used drugs. Cisplatin has strong anticancer activity, broad anti-cancer spectrum, but also has significantly kidney toxicity, ototoxicity, neurotoxicity, gastrointestinal toxicity and other adverse effect, and it is easy to induce drug resistance. Oxaliplatin is the third generation platinum drug, the anti-tumor activity is strong and anti-tumor spectrum is relatively narrow, and there is no cross-resistance with cisplatin. Compared with cisplatin, its side effects on renal toxicity, cardiac toxicity and gastrointestinal are significantly reduced; but it has obviously peripheral neurotoxicity. Lobaplatin is also the third generation platinum drug, its anticancer activity is strong, and its renal, neurological and gastrointestinal toxicity are mild compare to the other two drugs. For these advantages, lobaplatin may be used in the intraperitoneal chemotherapy. But currently the reports in the literature is few about it, and there is not sufficient data in vivo efficacy and pharmacokinetic characteristics.Objective:To providing theoretical basis of the feasibility, safety and efficacy of the using of lobaplatin for peritoneal perfusion in the treatment of gastrointestinal tumors through research on the inhibiting experiment on human colon cancer cells HCT-8, organ toxicity assessment on mice organ and the pharmacokinetic characteristics measurement in patients who accepted the intraperitoneal chemotherapy.Method:cell experiment:HCT-8 cells were seeded in 96-well plates at a density of 40,000 per well and were allocated to control group, thermotherapy group, lobaplatin group and laboplatin plus thermotherapy group. For the groups contained with lobaplatin, different drug concentration was setupped. The growth state of cells was observed under microscopy and the inhibition rates of each group were measured with assay.Animal experiments:cleaning degree mice was used for the experiment and were randomly divide into control group, oxaliplatin group, DDP group, lobplatin group, n=15. for each group, the mice was treated with intraperitoneal perfusion with different concentrations of chemotherapy drugs, the general living conditions of the mice and survival rate and so on were observed. And the histological changes of liver, kidney were observed under microscope.Clinical observation:Advance gastric carcinoma patients with peritoneal metastasis that diagnosed by pathology or cytology was select for the study, all patients was treated with intraperitoneal lobaplatin, then concentration of the drug in serum and in ascites are detect to clarify its pharmacokinetic characteristics, and pharmacodynamics. The side effects were observed.Results:The growth statu of HCT-8 cells were worse in experiment groups than that in the control group.Lobaplatin and thermotherapy can both inhibit the growth of tumor cells. In lobaplatin plus thermotherapy group the inhibition effect was mor obviously, synergy effect was observed.Cisplatin and oxaliplatin all can produce damage on the peritoneum, liver and kidney in different digree, but that was reversible. Lobapaltin does not have these side effects.In the Lobapaltin intraperitoneal perfusion treatment patients, high concentration of drug was sustained in ascites. The control effect of ascites was satisfied and the side effects were few.Conclusion:We observed that lobaplatin combined hyperthermia can inhibit cell growth synergistically, and present a concentration-time dependent model. Lobaplatin has mild liver and kidney toxicity compare to cisplatin and oxaliplatin, and can be used for intravenous and intraperitoneal therapy.Intraperitoneal chemotherapy has more obvious advantages in pharmacokinetics than intravenous chemotherapy alone.