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A Phase-III Randomized Controlled Trial of Nedaplatin Versus Cisplatin Concurrent Chemoradiotherapy in Patients with Cervical Cancer
15 Pages Posted: 31 Mar 2022
More...Abstract
Background: Cisplatin-based concurrent chemoradiotherapy is the standard care for cervical cancer patients. Unfortunately, this regimen is accompanied by side effects, including gastrointestinal reactions, nephrotoxicity, and ototoxicity. Nedaplatin-based concurrent chemotherapy is an alternative regimen to reduce the cisplatin-induced toxic effects. Thus, in this trial, we evaluated the non-inferiority of a nedaplatin-based concurrent chemoradiotherapy regimen and a cisplatin-based concurrent chemoradiotherapy regimen for patients with stage IB-IVA cervical cancer.
Methods: Patients aged between 28 and 82 years with pathologically diagnosed cervical cancer (stage IB-IVA) were randomly chosen for the study. All the patients have good hematologic, renal and hepatic function, and an Eastern Cooperative Oncology Group (ECOG) score of 0-2. Randomization was performed based on Microsoft Excel to assign patients (1:1) to the group of cisplatin and nedaplatin. Patients in both groups received radiotherapy (IMRT, 45-50.4 Gy in total) and a weekly-based intravenous nedaplatin 30 mg/m² or cisplatin 30 mg/m² concurrently. The primary endpoint was overall survival in the intent-to-treat population. All the randomly assigned patients who received at least one dose of the regimen received a safety analysis. This trial is registered on the Chinese Clinical Trial Registry, and the trial number is ChiCTR1800017108.
Findings: 160 patients who received treatment between May 10, 2018, and August 31, 2020, were included in the modified intention-to-treat analysis (80 in the nedaplatin group and 80 in the cisplatin group). The 3-year overall survival in the nedaplatin group (median 30.5 months) was not significantly different from that in the cisplatin group (28.5 months; hazard ratio 0.131, 95% CI 0.016–1.068; p=0.058, one-sided stratified log-rank test). The 3-year progression-free survival rate was higher in the nedaplatin group (median 30 months) than in the cisplatin group (28 months; hazard ratio 3.963, 95% CI 1.303–12.053; p=0.015), whereas FIGO (International Federation of Gynaecology and Obstetrics) stage classification has no difference in the two groups. No significant difference in the haematological toxicity and side effects was observed between the two groups. Vomiting (40 of 78 patients in the nedaplatin group and 61 of 79 in the cisplatin group), nausea (44 vs. 67), and anorexia (52 vs. 71) were more common in the cisplatin group; while effects on liver function, including total bilirubin (7 vs. 3), alanine aminotransferase (7 vs. 2), and aspartate aminotransferase (6 vs. 2) were more common in the nedaplatin group. Four patients in the cisplatin group had grade I creatinine elevations, while none in the nedaplatin group had abnormal creatinine levels. Two patients in the nedaplatin group discontinued concurrent chemotherapy due to infusion; and one patient in the cisplatin group discontinued due to infusion-induced dizziness. No treatment-related deaths occurred in the treatment.
Interpretation: Our findings suggest that nedaplatin has a milder gastrointestinal reaction but a more significant effect on liver function than cisplatin. In cervical cancer patients, nedaplatin-based concurrent chemoradiotherapy could serve as an alternative treatment for cisplatin-based concurrent chemoradiotherapy. Further research is required to explore the possibility of nedaplatin-based concurrent chemoradiotherapy as inductionchemotherapy, adjuvant chemotherapy
Trial Registration: This trial is registered on the Chinese Clinical Trial Registry, and the trial number is ChiCTR1800017108.
Funding: Youth Project of Shanghai Municipal Health Commission; Basic Research Project of the
Sixth People's Hospital Affiliated to Shanghai Jiao Tong University.
Declaration of Interest: The authors declare no conflict of interest.
Ethical Approval: The ethics committee approved the study protocol in our center, with all patients provided written informed consent.
Keywords: Cervical cancer, Nedaplatin, Cisplatin, Chemoradiotherapy
Suggested Citation: Suggested Citation