Relationship between outcomes and relative dose intensity of lenvatinib treatment in patients with advanced hepatocellular carcinoma

Background and aims:Lenvatinib(LEN)is a newly developed tyrosine kinase inhibitor,and is approved as a first-line treatment for advanced hepatocellular carcinoma(HCC)in Japan.This retrospective multi-center study investigated the effect of the relative dose intensity(RDI)of LEN on response rate,progression-free survival(PFS),and overall survival(OS).Methods:This retrospective study enrolled 123 patients with advanced HCC who were treated with LEN at six hospitals in Japan between March 2018 and December 2019.These patients were divided into two groups:RDI≥70%(RDI 70 group,N=70)or RDI<70%(control group,N=53)in the first 30 days.The following data were compared between groups:patient backgrounds,adverse events,treatment out-comes,PFS,and OS.PFS and OS were analyzed using the Kaplan-Meier method,followed by the log-rank test.To identify significant factors that contributed to response,PFS,and OS,multivariate analysis was performed using factors for which P-values were<0.10 in univariate analysis.Results:The proportion of patients with Child-Pugh class 5A was significantly greater in the RDI 70 group than that in the control group(64.3%vs.28.3%,P<0.01).Dose interruption due to adverse events was significantly more common in the control group.The response rate was significantly higher in the RDI 70 group than that in the control group(35.7%vs.11.3%,P<0.01).Median PFS was significantly longer in the RDI 70 group(9.4 vs.4.7 months,P<0.01).Multivariate analysis showed that RDI≥70%(hazard ratio(HR)=0.55,P=0.025),hypertension grade≥2(HR=0.47,P=0.019),and response(HR=0.52,P=0.033)were independently associated with improved PFS.Median OS was also significantly longer in the RDI 70 group(20.0 vs.13.3 months,P=0.045).Multivariate analysis showed that female sex(HR=0.33,P=0.034)and disease control(HR=0.31,P<0.01)were independently associated with improved OS.RDI≥70%was not statistically significant in multivariate analysis.Conclusions:Our study revealed the importance of achieving RDI≥70%in the first 30 days of treatment to maximize the effects of LEN。

Oral Xeloda plus bi-platinu two-way combined chemotherapy in treatment of advanced gastrointestinal malignancies

AIM： To compare the effect, adverse events, cost-effectiveness and dose intensity （DI） of oral Xeloda vs calcium folinate （CF）/5-FU combination chemotherapy in patients with advanced gastrointestinal malignancies, both combined with bi-platinu two-way chemotherapy.METHODS： A total of 131 patients were enrolled and randomly selected to receive either oral Xeloda （X group） or CF/5-FU （control group）. Oral Xeloda 1 000 mg/m^2 was administered twice daily from d 1 to 14 in X group, while CF 200 mg/m^2 was taken as a 2-h intravenous infusion followed by 5-FU 600 mg/m^2 intravenously for 4-6 h on d 1-5 in control group. Cisplatin and oxaliplatin were administered in the same way to both the groups： cisplatin 60-80 mg/m^2 by hyperthermic intraperitoneal administration, and oxaliplatin 130 mg/m^2 intravenouslyfor 2 h on d 1. All the drugs were recycled every 21 d, with at least two cycles. Pyridoxine 50 mg was given t.i.d. orally for prophylaxis of the hand-foot syndrome （HFS）. Then the effect, adverse events, cost-effectiveness and DI of the two groups were evaluated.RESULTS： Hundred and fourteen cases （87.0%） finished more than two chemotherapy cycles. The overall response rate of them was 52.5% （X group） and 42.4% （control group） respectively. Tumor progression time （TTP） was 7.35 mo vs5.95 too, and 1-year survival rate was 53.1% vs 44.5%. There was a remarkable statistical significance of TTP and 1-year survival between the two groups. The main Xelocla-related adverse events were myelosuppression, gastrointestinal toxicity, neurotoxicity and HFS, which were mild and well tolerable. Therefore, no patients withdrew from the study due to side effects before two chemotherapy cycles were finished. Both groups finished pre-arranged DI and the relative DI was nearly 1.0. The average cost for 1 patient in one cycle was ￥9 137.35 （X group） and ￥8 961.72 （control group）, or US ＄1 100.89 in X group and ＄1 079.73 in control group. To add 1% to the response rate costs ￥ 161.44 vs ￥210.37 respectively （US ＄19.45 vs ＄25.35）. One-month prolongation of TTP costs ￥1 243.18 vs ￥1 506.17 （US ＄149.78 vs ＄181.47）. Escalation of 1% of 1-year survival costs ￥172.74 vs ￥201.64 （US ＄20.75 vs ＄24.29）. CONCLUSION： Oral Xeloda combined with bi-platinu two-way combination chemotherapy is efficient and tolerable for patients with advanced gastrointestinal malignancies; meanwhile the expenditure is similar to that of CF/5-FU combined with bi-platinu chemotherapy, and will be cheaper if we are concerned about the increase of the response rate, TTP or 1-year-survival rate pharmacoeconomically.