Mecobalamin Tablets Combined With Pyridoxine For Capecitabine-associated Hand Foot Syndrome:a Clinical Observation And Study

Objective:To compare the efficacy of mecobalamin tablets combined with large doses of pyridoxine in preventing or delaying the onset of hand foot syndrome (HFS) in capecitabine treated patients.Methods:Collecting datas of 80 inpatients or outpatients wih histologically confirmed gastric cancer, colorectal cancer or breast cancer receiving single agent capecitabine or combination chemotherapy contianing capecitabine in Gastrointestinal Surgery of Shandong Provincial Hospital affiliated to Shandong University, from December 2013 to February 2015, which age form 18 to 85, KPS from 80 to 100. Capecitabine started at 2500mg/m2 daily from 1 to 14 days every 3 weeks for 6 to 8 cycles. The patients were randomly assigned to two groups. Group A were prophylaxis group received mecobalamin tablets (0.5mg, po,3 times daily) combined with large doses of pyridoxine(100mg, po,3 times daily) for HFS prophylaxis. Group B were control group only received large doses of pyridoxine(100mg, po,3 times daily) for HFS prophylaxis. The primary endpoint was to compare the incidence of HFS between Group A and Group B. The secondary endpoints were to compare the time of HFS begining and adverse reaction between Group A and Group B. The datas were analysized using SPSS 19.0, which classified variable analysized by χ2 test or Fisher’s exact test, which numerical variable analysized by t test. The time of HFS begining described by Kaplan-Meier method and group comparing testing by Log-rank test. The test standard a=0.05(two side) and P<0.05 represent had statistical significance.Results:There were 76 patients completed the study. Because the reasons of losing, poor compliance or income, four patients exited the study including one in Group A and three in Group B. The baseline characteristics (such as sex、KPS、pathology, et al) were generally similar compared 39 patients in Group A and 37 patients in Group B (P>0.05).1.The incidence of HFS in Group A and Group B were 12.8%、32.4%, there were a significant difference among the two groups(χ2=4.21 P=0.04<0.05). Group A do not occurs grade three HFS and did not have any patients induced the dose of capecitabine. One patient in Group A occurs grade three HFS and the dose of capecitabine induced to 75% of primary doses.2.The occurrence time of HFS in Group A and Group B were 81.40+6.07 days and 71.08±7.17 days, the median time to the development of HFS in Group A and Group B were 84 days and 72 days, there were a significant difference among the two groups through the Log-rank test(χ2=5.807 P=0.016<0.05).3.The adverse reaction main had nausea、vomiting、myelosuppression、diarrhea、 constipation、fatigue、dizzy、stomatitis except HFS. The grade of nausea and vomiting according to WHO standard, Group A had 21 patients in grade 1,7 patients in grade 2, 2 patients in grade 3,1 patients in grade 4. Group B had 18 patients in grade 1,9 patients in grade 2,1 patient in grade 3, no patients in grade 4. The incidence of nausea and vomiting and grade 3-4 incidence of nausea and vomiting were 79.5%VS75.7% and 7.7%VS2.7% compared with two groups. The were not a significant difference among the two groups (χ2=0.16 P=0.690>0.05 and χ2=0.21 P=0.646>0.05). The grade of myelosuppression according to WHO standard, Leucopenia:Group A had 8 patients in grade 1,2 patients in grade 2. Group B had 10 patients in grade 1,2 patients in grade 2; Thrombocytopenia:Group A had 5 patients in grade 1,1 patients in grade 2. Group B had 4 patients in grade 1, no patients in grade 2; Neutrophil count decreased:Group A had 11 patients in grade 1,7 patients in grade 2. Group B had 7 patients in grade 1,3 patients in grade 2. The were not a significant difference among the two groups(P>0.05). Besides, Group A:10 patients occured diarrhea 、2 patients occured constipation、3 patients occurred stomachache> 2 patients occured fatigue、2 patients occured dizzy、1 patients occured stomatitis. Group B:8 patients occured diarrhea、1 patients occured constipation、2 patients occurred stomachache、1 patients occured fatigue、4 patients occured dizzy、2 patients occured stomatitis. The incidence of adverse including diarrhea、constipation、 stomachache、fatigue、dizzy、stomatitis did not have a significant difference among the two groups(P>0.05).Conclusion:1.It can decreased the incidence of HFS compared with Group A and Group B.2. It can prolong the occurrence time of HFS compared with Group A and Group B.3.The incidence of nausea and vomiting in Group A was higher than Group B, but the were not a significant difference among the two groups(P>0.05). The incidence of adverse reactions including myelosuppression、diarrhea、constipation、stomachache、 fatigue、dizzy、stomatitis did not have a significant difference among the two groups(P>0.05). It prompt us that mecobalamin tablets combined with large doses of pyridoxine in preventing or delaying the onset of hand foot syndrome (HFS) in capecitabine treated patients have better security.