Randomized phase III trial of radiotherapy or chemoradiotherapy with topotecan and cisplatin in intermediate-risk cervical cancer patients after radical hysterectomy.
BACKGROUND
In cervical cancer patients with intermediate-risk factors, the optimal adjuvant therapy is still controversial. We undertook a randomized trial (ClinicalTrials.gov Identifier: NCT01418859) to compare the efficacy and toxicity of concurrent chemoradiotherapy with topotecan and cisplatin with radiotherapy alone in intermediate-risk cervical cancer patients.


METHODS
Eligible patients were randomly assigned to one of three treatment arms including arm A (radiotherapy only,RT), arm B(concurrent chemoradiotherapy only, CCRT), and arm C (concurrent chemoradiotherapy with following consolidation chemotherapy, CCRT + CT). All eligible patients completed external RT (IMRT or 3D-CRT), receiving 45-50 Gy /25 f uniformly to the pelvis. Concurrent chemotherapy regimen was topotecan 0.75 mg/m(2) for days 1, 2 and 3, followed by cisplatin 25 mg/m(2) for days 1, 2 and 3. Three cycles of consolidation chemotherapy regimen was topotecan 1.5 mg/m(2) for days 1 and 2, and 0.75 mg/m(2) for day 3; followed by cisplatin 25 mg/m(2) for days 1, 2 and 3, repeated every 21 days. Adverse events of each group were investigated and compared.


RESULTS
Thirty-nine patients enrolled onto the remaining regimens: 14 to RT, 15 to CCRT and 10 to CCRT + CT. Six patients (15.4%) did not complete the protocol treatment. Hematologic toxicity was more frequent and more severe in the CCRT and CCRT + CT arms compared with the RT arm. The incidence of grade 3-4 neutropenia was significantly different statistically between the RT, CCRT and CCRT + RT groups (15.4%, 46.7% and 100%, respectively; P = 0.002). Specially, three patients in CCRT + CT arm of all six patients who did not complete the protocol treatment discontinued planned therapy because of persistent grade 4 neutropenia. However, there were no significant differences in grade 3-4 non-hematologic toxicities between the three groups(all P > 0.05). Recurrence-free survival and overall survival of each group were not analyzed on account of a median follow-up of only 16 months.


CONCLUSIONS
Concurrent chemoradiotherapy with topotecan and cisplatin showed severe hematologic toxicity in intermediate-risk cervical cancer patients after radical hysterectomy. Thus, the study was closed ahead of schedule.


BACKGROUND
ClinicalTrials.gov Identifier: NCT01418859 .
Department of Radiation Oncology, First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Yanta District, Xi'an, 710061, China. swz032021511986@163.com.
Wenze
W
Sun
Department of Radiation Oncology, First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Yanta District, Xi'an, 710061, China. wangtaoxjtu@126.com.
Tao
T
Wang
Department of Radiation Oncology, First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Yanta District, Xi'an, 710061, China. shifanxjtu@126.com.
Fan
F
Shi
Department of Radiation Oncology, First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Yanta District, Xi'an, 710061, China. wangjiquanxjtu@126.com.
Jiquan
J
Wang
Department of Radiation Oncology, First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Yanta District, Xi'an, 710061, China. wangjuanxjtu@126.com.
Juan
J
Wang
Department of Radiation Oncology, First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Yanta District, Xi'an, 710061, China. huibeinaxjtu@126.com.
Beina
B
Hui
Department of Radiation Oncology, First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Yanta District, Xi'an, 710061, China. zhangyingbingxjtu@126.com.
Yingbing
Y
Zhang
Department of Radiation Oncology, First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Yanta District, Xi'an, 710061, China. lujinlixjtu@126.com.
Jinli
J
Lu
Department of Radiation Oncology, First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Yanta District, Xi'an, 710061, China. chenhongweixjtu@163.com.
Hongwei
H
Chen
Department of Radiation Oncology, First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Yanta District, Xi'an, 710061, China. liuzmail@163.com.
Zi
Z
Liu
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D059186:Chemoradiotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007044:Hysterectomy; D008875:Middle Aged; D012306:Risk; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000628:therapy*
D019772:Topotecan; D002945:Cisplatin