Randomized phase III trial of radiotherapy or chemoradiotherapy with topotecan and cisplatin in intermediate-risk cervical cancer patients after radical hysterectomy
Mené sur 39 patientes atteintes d'un cancer de l'utérus à risque intermédiaire de récidive et traitées par hystérectomie, cet essai de phase III compare la toxicité de trois stratégies thérapeutiques comportant une radiothérapie en combinaison ou non avec une chimiothérapie concomitante par topotécan et cisplatine
Résumé en anglais
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 45-50Gy /25f uniformly to the pelvis. Concurrent chemotherapy regimen was topotecan 0.75 mg/m2 for days 1, 2 and 3, followed by cisplatin 25 mg/m2 for days 1, 2 and 3. Three cycles of consolidation chemotherapy regimen was topotecan 1.5 mg/m2 for days 1 and 2, and 0.75 mg/m2 for day 3; followed by cisplatin 25 mg/m2 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. Trial registration ClinicalTrials.gov Identifier: NCT01418859.
