ABSTRACT
Objective To determine the maximum tolerated dose ( MTD) and dose?limiting toxicity ( DLT) of weekly PTX and DDP concurrent postoperative radiotherapy in Chinese women with high?and intermediate?risk early cervical cancer. Methods Women with high risks postoperative cervical carcinoma, ECOG≤2 were eligible. Pelvis RT (6/10 MV X?ray,3DCRT 40 Gy/20f,para?metrial boost 10?20 Gy/5?10f) was followed by 2?4f brachytherapy applications ( 192 Ir,5 Gy/f) . Concurrent weekly chemotherapy was started at DDP 20 mg/m2 and PTX 10 mg/m2 weekly,and escalated in three?patient cohorts according to 3+3 methods. Results 25 patients were enrolled and treated over seven doses levels until dose?limiting toxicity (DLT) was reached. Median age was 48 years (range,34?66).All of patients finished RT in 7 weeks. Grade 3,4 non?hematologic toxicities were diarrhea and observed in two patients (4 cycles,DLT) at level 7.Grade 3,4 hematologic,principally leukopenia and neutropenia,and occurs late cycles. One grade 4 leukopenia and neutropenia was observed at dose level 6 but not seen in three additional patients. No one was delayed treatment time by concurrent chemotherapy.22 patients finished 6 cycles. Median follow?up is 59. 5 months. Three patients have died of cancer metastasis and recurrence. One patient has died of respiratory failure. Conclusions Combination PTX and DDP administered concurrently with pelvic EBRT can be safely administered at the MTD of DDP 35 mg/m2 and PTX 30 mg/m2 weekly for six cycles in Chinese women with postoperative cervical cancer.
ABSTRACT
Objective To investigate the proteomics differences between the high-sensitivity(HS) and the low-sensitivity(LS)groups of cervical carcinoma treated by concurrent chemoradiotherapy,and to confirm the sensitivity associated proteins in intermediate stage and advanced cervical carcinoma.Methods Fresh carcinoma tissues were collected from 10 untreated cervical carcinoma patients.According to the response to concurrent chemoradiotherapy,the tissues were classified into HS group and LS group.In the first part of our experiment,protein separation was performed using two-dimensional gel electrophoresis(2-DE)with Amersham 18 am linear pH 3-10 immobilized pH gradient(IPG)strips.The images of the gels were analyzed by PD-quest 7.0 software to find the differentially expressed protein-spots in each group.Then the differentially expressed protein-spots were incised from the gels and digested by trypsin.The peptide mass flngerprintings(PMF)was acquired by matrix assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS).The proteins were identified by data searched in the Mascot-database.Two differentially expressed proteins were assayed by western blot and immunohistochemical methods.Results Most of the gels were clear and successfully analyzed by PD-quest 7.0 software.Most of the protein-spots concentrated on the area of 20-100 KDa(Mw)and pH4-8.The average number of the protein-spots was 781±74 in HS group and 766±52 in LS group.The match rate was 87.6%between the two groups.Eight proteins highly in HS group but lowly expressed in LS group included hemoglobin subunit beta,caspase-14 precursor,calmodulin-like,S100-A9 protein(MRP-14),galectin-7,HSKERC4,keratin 19 and actin.Ten proteins highly in LS group but lowly expression in HS group included anti HBs antibody light-chain Fab,laminB1,WARS protein,flavin reductase,glutamate dehydrogenase 1,nuclear matrix protein 238,retinal dehydrogenase 1,AFl 65172,subunit of replicative DNA polymerase and HSP70.The higher expression of HSP70 in LS group and galectin7 in HS groups were further confirmed by western blot and immunohistochemical method.Conclusions The 2-DE gels images are successfully acquired from high-sensitivity group and low-sensitivity group of intermediate stage and advanced cervical carcinoma tissues treated by concurrent chemoradiotherapy.Some differentially expressed proteins between the two groups can be further confirmed by western blot and immunohistochemical method.