Genomic DNA detection frequently-used chemotherapeutic drugs and their adverse drug reactions in children with rhabdomyosarcoma
10.3760/cma.j.issn.2095-428X.2019.21.009
- VernacularTitle: 儿童横纹肌肉瘤常用化疗药物基因组DNA检测及其与药物不良反应的关系
- Author:
Xi CHAI
1
;
Yiwei LIU
2
;
Mei JIN
1
;
Yan SU
1
;
Wen ZHAO
1
;
Qian ZHAO
1
;
Shengcai WANG
3
;
Lejian HE
2
;
Hong QIN
4
;
Huanmin WANG
4
;
Weiping ZHANG
5
;
Ning SUN
5
;
Xiaoling WANG
2
;
Xiaoli MA
1
Author Information
1. Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics(Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Hematology Oncology Center, Beijing Children′s Hospital, Capital Medical University, National Center for Children′s Health, Beijing 100045, China
2. Clinical Research Center, Beijing Children′s Hospital, Capital Medical University, National Center for Children′s Health, Beijing 100045, China
3. Department of Otorhinolaryngology Head and Neck Surgery, Beijing Children′s Hospital, Capital Medical University, National Center for Children′s Health, Beijing 100045, China
4. Department of Oncology Surgery, Beijing Children′s Hospital, Capital Medical University, National Center for Children′s Health, Beijing 100045, China
5. Department of Urological Surgery, Beijing Children′s Hospital, Capital Medical University, National Center for Children′s Health, Beijing 100045, China
- Publication Type:Journal Article
- Keywords:
Rhabdomyosarcoma;
Side effect;
Pharmacogenomics;
Irinotecan
- From:
Chinese Journal of Applied Clinical Pediatrics
2019;34(21):1635-1639
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze and summarize the results of genomic DNA test findings of chemotherapeutic drugs commonly used in pediatric rhabdomyosarcoma (RMS) in children, and to analyze the relationship between adverse reactions to chemotherapy toxicity and genomic DNA polymorphisms, so as to provide evidence for guiding treatment.
Methods:Retrospective analysis was conducted in RMS children admitted at Hematology Oncology Center, Beijing Children′s Hospital, Capital Medical University from January 2017 to June 2018.The criteria for enrollment were definite diagnosis of RMS, regular treatment and follow-up at Hematology Oncology Center, Beijing Children′s Hospital, Capital Medical University, and detection of peripheral blood DNA fluorescence hybridization sequence for several commonly chemotherapy drugs.The toxicity of chemotherapeutic drugs was detected based on the National Cancer Institute routine toxicity criteria (NCI-CTCAE version 4.0). Summary and analysis indicators included primary and metastatic site, size, international RMS clinical stage (TNM-UICC), Intergroup Rhabdomyosarcoma Study(IRS) Clinical Grouping Classification, risk grouping, pathological type, changes in major organ functions, as well as processes of surgery, chemotherapy and radiotherapy, and the association between toxicity and DNA polymorphism of drug genes was analyzed.SPSS 22.0 software was used for χ2 test.
Results:A total of 32 children were enrolled, and 20 cases were male and 12 cases were female, their median age was 50 months (15-120 months). The primary tumor of 9 cases were sited in the chest, abdomen and basin, 8 cases in the head and neck (non-meningeal), 7 cases in bladder prostate, 3 cases in limbs, 2 cases in the meningeal area, 1 case in urogenital tract (non-bladder prostate), 2 cases in other parts.Seventeen cases were embryonic type and 15 cases were alveolar type.Five cases were TNM-Ⅰ stage, 5 cases were TNM-Ⅱ stage, 10 cases TNM -Ⅲ stage, 12 cases were TNM-Ⅳ stage, 21 cases were IRS-Ⅲ, 11 cases were IRS-Ⅳ.Twenty-two cases were moderate-risk (MR), 10 cases were high-risk (HR). Twenty-two cases were detected UGT1A1*6 gene, 18 cases in GG type, 13 cases in GA type, and 1 case in AA type.ABCB1 gene monitoring was performed in 27 children, 14 cases of CT type and 13 cases of TT type; 29 cases were detected GSTP1 gene, 7 cases of GA type and 2 cases of GG type, 19 cases of AA type, 1 case of AG type; 30 cases were detected CYP3A5 gene, 2 cases of GA type, 13 cases of GG type, AG 15 cases.All patients were treated according to the BCH-RMS-2007 protocol using VAC (Vincristine, Doxorubicin, and Cyclophosphamide) as the basis for chemotherapy.From 2017, VAC and VI regimen (Vincristine, Irinotecan) were defined as the standard of backbone chemotherapeutic regimen for MR.Nine cases underwent surgery before chemotherapy and 10 cases had surgery after chemotherapy, among them, 5 cases underwent twice operation.Local radiotherapy was performed on the 12th week of chemotherapy, and the central nervous system involvement cases started in the first week.Hematological toxicity was mainly caused by neutropenia, with 2 cases of grade 3 and 30 cases of grade 4.Liver function damage of grade 2 was 6 cases, grade 3 was 3 cases.Four patients with grade 1 diarrhea, 3 patients with grade 2, 5 patients with grade 3, 3 patients with grade 4.There was significant diffe-rence between the severity of diarrhea and UGT1A1*6 genotype polymorphism(P<0.05).
Conclusions:Chemothe-rapy for RMS patients is highly safety.If the genomic DNA test of chemotherapy drugs show a slow metabolism type, the dose of chemotherapy should be reduced, and the toxicity of chemotherapy drugs should be monitored dynamically.
