Study Of Recombinant Human Thrombopoietin On The Secondary Prevention Of Thrombocytopenia-induced By Oxaliplatin-containing Chemotherapy

Objective:To evaluate the clinical efficacy and safety of recombinant human thrombopoietin on the secondary prevention of thrombocytopenia-induced by oxaliplatin-containing chemotherapy,and explore its applicable people.Method:87 patients with digestive tract malignant tumors who were treated with oxaliplatin-containing chemotherapy regimens(XELOX,FOLFOX,SOX)and diagnosed as grade Ⅱ～Ⅲ thrombocytopenia or grade Ⅰ thrombocytopenia recovering after being treated for≥7 days using recombinant human thrombopoietin were prospectively enrolled from August 2019 to August 2020.Those patients were divided into two groups according to the patient’s wishes,namely the rhTPO secondary prevention group(n=39 cases)before subsequent chemotherapy and the rhTPO conventional treatment after subsequent chemotherapy Group(n=48 cases).The method of intergroup control and self-control were used for the comparative analysis of the lowest platelet count,the rate of recurrence of CIT,the reduction rate of chemotherapy drugs,the delay rate of chemotherapy,the length of stay,the hospitalization expenses,the number of subsequent chemotherapy cycles,the total number of tolerable chemotherapy cycles,and the total exposure of oxaliplatin.The lowest platelet value,length of hospitalization and hospitalization expenses before and after prevention in the rhTPO secondary prevention group were also analyzed.The χ2 test,non-parametric rank sum test,independent-samples T test and paired-samples T test were mainly used to compare the general data of the two groups.P>0.05 is considered to be insignificant,P<0.05 is considered to be statistically significant,and P<0.01 is considered to be very statistically significant.Results:1.Comparative between the secondary prevention group and conventional treatment group.(1)The lowest value of platelet:The lowest platelet count in observation period 1 to 3 was(135.0±65.2)xiO9/L in secondary prevention group and(73.9± 12.1)×109/L in conventional treatment group,P=0.000;the lowest platelet count in the first observation period was(134.6± 127.0)×109/L in secondary prevention group and(73.8± 11.7)x109/L in conventional treatment group,P=0.000;the lowest platelet count in the second observation period were(132.0±86.8)×109/L and(76.7± 14.5)×109/L in two group,respectively,P=0.000;the lowest platelet count in the third observation period were(140.1±46.7)×109/L and(75.1±8.5)×109/L in two group,respectively,P=0.002.(2)The rate of recurrence of CIT of the first cycle was 33.3%in secondary prevention group and 52.1%in conventional treatment group(P>0.05),and the rate of recurrence of CIT in the secondary prevention group tended to decrease.(3)The time for platelets to return to normal of the first cycle was(4.0± 1.7)days in secondary prevention group and(6.9± 1.7)days in conventional treatment group(P>0.05),and time platelets to return to normal after the occurrence of CIT again in the secondary prevention group tended to decrease.(4)The rate of reduction of chemotherapy drugs of the first cycle was 17.9%in secondary prevention group and 29.3%in conventional treatment group(iP=0.227),and the rate of reduction of chemotherapy tended to decrease.(5)The rate of chemotherapy delay of the first cycle was 23.1%in secondary prevention group and 95.8%in conventional treatment group(P=0.000).(6)The tolerable median follow-up chemotherapy cycles are 3 cycles in secondary prevention group and 2 cycles in conventional treatment group(P=0.000).(7)The median total number of chemotherapy cycles was both 6 cycles in two groups,P=0.619.(8)The total exposure to oxaliplatin was(982.8±290.7)mg in secondary prevention group and(947.2±332.3)mg in conventional treatment group(P=0.600).(9)The length of hospital stay in the secondary prevention group tended to decrease.The total length of median hospital stay in the secondary prevention group was 26 days and 38 days in the conventional treatment group,P=0.024;the median length of stay in the first observation period was 4 days in secondary prevention group and 11 days in conventional treatment group,P=0.000;the median length of stay in the second observation period were 4 days and 8 days in two group,respectively,P=0.816;the length of stay in the third observation period were 5 days and 7 days in two group,respectively,P=0.281.(10)The total hospitalization costs were(86505.2±31254.2)yuan in the secondary prevention group and(92011.1±56303.8)yuan in the conventional treatment group,respectively,P=0.738;the hospitalization expenses in the first observation period was(13132.6±5235.7)yuan in secondary prevention group and(21057.819581.6)yuan in conventional treatment group,P=0.000;the hospitalization expenses in the second observation period were(12676.0±6643.4)yuan and(13257.5±7551.7)yuan in two group,respectively,P=0.784;the hospitalization expenses in the third observation period were(9430.9±3386.1)yuan and(9126.9±3388.9)yuan in two group,respectively,P=0.533.2.Comparation of clinical efficacy before and after prevention.(1)The lowest value of platelet:The lowest platelet count was(161.9163.0)×109/L in the first preventive cycle and(63.9±13.2)×109/L in cycle before prevention,P=0.000;the lowest platelet count was(132.1±86.6)×109/L in second preventive cycle and(62.0±12.5)×109/L in cycle before prevention,P=0.003;the lowest platelet count was(140.1 146.7)×109/L in third preventive cycle and(65.3±16.7)×109/L in cycle before prevention,P=0.001.(2)The length of hospital stay:The median length of hospital stay was 4 days in the first preventive cycle and 10 days in cycle before prevention,P=0.001;the median length of stay was 4 days in second preventive cycle and 8 days in cycle before prevention,P=0.463;the median length of hospital stay was 4 days in third preventive cycle and 12 days in cycle before prevention,P=0.027.(3)The hospitalization expense:The hospitalization expense was(13042.3±5293.3)yuan in the first preventive cycle and(20358.5±6463.5)yuan in cycle before prevention,P=0.000;the hospitalization expense was(11817.6±5567.7)yuan in second preventive cycle and(19199.4±7439.6)yuan in cycle before prevention,P=0.000;the hospitalization expense was(13859.5±7640.6)yuan in third preventive cycle and(18403.6±9683.9)yuan in cycle before prevention,P=0.176.3.The efficacy of secondary prevention in different populations.(1)The lowest platelet was(127.1 ±54.4)×109/L in people with grade Ⅱ～Ⅲ CIT and(142.3±72.6)×109/L in those with grade I CIT recovering after being treated for≥7 days using recombinant human thrombopoietin in the first preventive cycle,P=0.516;(126.3±42.3)×109/L and(109.2±50.9)×109/L in the second preventive cycle,P=0.504;(158.2±53.7)×109/L,and(110.7±55.2)×109/L in the third preventive cycle,P=0.390.(2)The lowest platelet count in first preventive cycle were(138.6±30.6)×109/L in people receiving oral fluorouracil chemotherapy and(180.4±94.6)×109/L in people receiving intravenous fluorouracil,P=0.128;(104.8±25.2)×109/L and(119.5±32.3)x109/L in second preventive cycle,P=0.378;the lowest platelet values in the third cycle of prevention were(172.0±54.2)×109/L,(122.3±60.1)×109/L in third preventive cycle,P=0.403.4.The safety of recombinant human thrombopoietin on the secondary prevention of thrombocytopenia-induced by oxaliplatin-containing chemotherapy is good.Conclusion:(1)For patients with thrombocytopenia-induced by oxaliplatin-containing regimens,the secondary preventive treatment of rhTPO has good efficacy.And the safety is good.(2)The use of recombinant human thrombopoietin on the secondary prevention of thrombocytopenia can reduce the severity of thrombocytopenia,shorten the time from the occurrence of CIT to the platelet return to normal,shorten the length of stay,reduce the hospitalization expenses,decrease the occurrence of chemotherapy delay,ensure the intensity of chemotherapy dose and efficacy of chemotherapy.(3)The patients with digestive tract malignant tumors who are diagnosed as grade II-III CIT and who were diagnosed as grade≥Ⅰ CIT and treated with rhTPO for platelet-increasing therapy for≥7 days may be suitable for preventive use of thrombopoietin and may be the potential advantage groups.(4)The regimes of given 2,4,6,8 days rhTPO(15000 U/d)secondary prevention in patients receiving chemotherapy of XELOX and SOX,and 2,4,6 days rhTPO(15000 U/d)secondary prevention in patients receiving chemotherapy of FLOFOX were clinically practical.(5)This study is a small-sample,single-center clinical study,and the sample size needs to be further expanded for verification.