The Clinical Study Of First And Second Line Treatment Of Irinotecan Combined With Platinum In Small Cell Lung Cancer

Objective To observe the efficacy and safety of irinotecan combined with platinum in initial and recurrence small cell lung cancer, to explore the relationship between the genic polymorphism of UGT1A1and diarrhea.Method98previously-untreated extensive-stage small cell lung cancer patients were randomly assigened to irinotecan and cisplatin (IP) or etoposide and cisplatin(EP) group. All patients received at least two cycles of chemotherapy. The therapeutic effect and toxicity were carefully evaluated. UGT1A1*28and UGT1A1*6genotype of IP group were detected and relationships between the UGTIA1gene polymorphisms and toxicity were analyzed in second part of the study.87relaps SCLC patients were enrolled,43of them were treated with irinotecan and nedaplatin (IN), and rest of patients were treated with cyclophosphamide, epirubicinn and vincristine(CAV). The efficacy and toxicity were evaluated after the treatment.Results For the initial treatment of patients in extensive stage SCLC, the disease control rates (DCR) of IP group was81.3%, while the EP group was72%.There was significant difference between the two groups (P=0.043). The median PFS and median OS of IP group were6.8months and15.8months, the one-year and two-year survival rate was70.3%and25.2%respectively. The median PFS and median OS of EP group were6months and14.8months, the one-year and two-year survival rate were58.7%and15.4%respectively. There was no significant difference between the two groups. The incidence of diarrhea in IP group was54.1%, EP group was20.0%, there was significant difference (P=0.018). The Logistic multivariate analysis showed that UGTIAI*28genotype, ECOG status and the duaration of chemotherapy significantly impact on the level of â… -â…£ Grade delayed diarrhea. For the patients of recurrencent SCLC, the ORR of IN group was39.5%and20.5%in CAV group, there was significant difference (P=0.031) between the two groups. The median PFS and OS of IN group was3.3months and6.3months respectively. The one-year and two-year survival rate of IN group were24.1%and10.2%. The median PFS and OS of CAV group were2.4months and4.0months. the one-year and two-year survival rate of CAV were18.5%and8.1% respectively. No significant differences can be found between the two groups (P>0.05). There was no significant difference between the two groups in thems of hematological toxicity (P>0.05). The diarrhea incidence of IN group was37.2%vs11.4%in CAV group, there was significant difference (P=0.003). The alopecia of the CAV group was40.9%, significantly higher than the IN group which was18.6%,(P=0.005).Conclusion Irinotecan combined with platinum regimen were effective in small cell lung cancer of first and second line setting. UGT1A1gene polymorphism was relevant with delayed diarrhea.