Dataset Information

Phase III study of cisplatin with or without S-1 in patients with stage IVB, recurrent, or persistent cervical cancer.

ABSTRACT:

Background

This open-label phase III trial evaluated efficacy and safety of S-1 plus cisplatin vs. cisplatin alone as first-line chemotherapy in patients with stage IVB, recurrent, or persistent cervical cancer.

Methods

Patients were randomised (1:1) to S-1 plus cisplatin (study group) or cisplatin alone (control group). In each cycle, cisplatin 50 mg/m² was administered on Day 1 in both groups. S-1 was administered orally at 80-120 mg daily on Days 1-14 of a 21-day cycle in the study group. The primary endpoint was overall survival (OS).

Results

A total of 375 patients were enrolled, of whom 364 (188, study group; 176, control group) received treatment. Median OS was 21.9 and 19.5 months in the study and control groups, respectively (log-rank P = 0.125; hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.67-1.05). Median progression-free survival (PFS) was 7.3 and 4.9 months in the study and control groups, respectively (HR 0.62, 95% CI 0.48-0.80, P < 0.001). The adverse event (AE) rate increased in the study group despite the absence of any unexpected AEs.

Conclusions

S-1 plus cisplatin did not show superiority over cisplatin alone in OS but significantly increased PFS in patients with stage IVB, recurrent, or persistent cervical cancer. Since the standard therapy has changed in the course of this study, further studies are warranted to confirm the clinical positioning of S-1 combined with cisplatin for this population.

SUBMITTER: Aoki Y

PROVIDER: S-EPMC6162273 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:PurposeCombining cisplatin or cetuximab with radiation improves overall survival (OS) of patients with stage III or IV head and neck carcinoma (HNC). Cetuximab plus platinum regimens also increase OS in metastatic HNC. The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiation-cisplatin platform improves progression-free survival (PFS).Patients and methodsEligible patients with stage III or IV HNC were randomly assigned to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Acute and late reactions were scored using Common Terminology Criteria for Adverse Events (version 3). Outcomes were correlated with patient and tumor features and markers.ResultsOf 891 analyzed patients, 630 were alive at analysis (median follow-up, 3.8 years). Cetuximab plus cisplatin-radiation, versus cisplatin-radiation alone, resulted in more frequent interruptions in radiation therapy (26.9% v. 15.1%, respectively); similar cisplatin delivery (mean, 185.7 mg/m2 v. 191.1 mg/m2, respectively); and more grade 3 to 4 radiation mucositis (43.2% v. 33.3%, respectively), rash, fatigue, anorexia, and hypokalemia, but not more late toxicity. No differences were found between arms A and B in 30-day mortality (1.8% v. 2.0%, respectively; P = .81), 3-year PFS (61.2% v. 58.9%, respectively; P = .76), 3-year OS (72.9% v. 75.8%, respectively; P = .32), locoregional failure (19.9% v. 25.9%, respectively; P = .97), or distant metastasis (13.0% v. 9.7%, respectively; P = .08). Patients with p16-positive oropharyngeal carcinoma (OPC), compared with patients with p16-negative OPC, had better 3-year probability of PFS (72.8% v. 49.2%, respectively; P < .001) and OS (85.6% v. 60.1%, respectively; P < .001), but tumor epidermal growth factor receptor (EGFR) expression did not distinguish outcome.ConclusionAdding cetuximab to radiation-cisplatin did not improve outcome and hence should not be prescribed routinely. PFS and OS were higher in patients with p16-positive OPC, but outcomes did not differ by EGFR expression.

Project description:ObjectiveWe aimed to analyse the clinical value of primary site surgery in improving the cancer-specific survival (CSS) and overall survival (OS) of initial metastatic cervical cancer patients.DesignA population-based retrospective study.SettingNational Cancer Institute's Surveillance, Epidemiology and End Results database.ParticipantsWe analysed 1390 patients with the International Federation of Gynecology and Obstetrics 2009 stage IVB cervical cancer with complete clinical data treated between 2010 and 2016.InterventionsPrimary site surgery.MeasuresPropensity score matching (PSM) with a ratio of 1:2 was used to balance measure covariates of comparison groups. Survival time was calculated using Kaplan-Meier methods and compared by the log-rank test. To eliminate the bias of site-specific metastasis, clinicopathological factors and subsequent therapy on survival analysis, subgroup analyses stratified by metastasis type, clinicopathological factors and subsequent therapy were employed to evaluate the effect of cervical surgery on survival. Combination of directed acyclic graph and change-in-estimate procedures was performed to indentified confounders, and Cox regression was used to assess the survival benefit of cervical surgery for primary metastatic cervical cancer patients. The consistency of our findings was evaluated through sensitivity analysis.ResultsMatching resulted in two comparison groups with minor differences in most variables. Pre-and-post-PSM, the median CSS and OS in the surgery group were 1.3 and 1.5, 1.1 and 1.2 times of those in the non-surgery group, respectively. Primary site surgery conferred prognosis superiority for patients with metastases to distant lymph node and other sites rather than organ metastases. After PSM and adjusting confounders, local surgery reduced the cancer related and overall mortality rates by 31% and 30%, respectively.ConclusionsSurgical procedures could promote survival in patients with primary metastatic cervical cancer and should be considered a therapeutic option for carefully chosen patients.

Project description:BackgroundNo novel chemotherapeutic combinations have demonstrated superior efficacy to etoposide/cisplatin (EP), a standard treatment regimen for extensive-stage small cell lung carcinoma (ES-SCLC) over the past decade. We aimed to compare the efficacy and safety of belotecan/cisplatin (BP) and EP regimens in chemotherapy- and radiotherapy-naïve patients with previously untreated ES-SCLC.MethodsWe conducted a multi-center, randomized, open-label, parallel-group, phase III clinical study. A total of 157 patients were recruited at 14 centers with 147 patients meeting the inclusion/exclusion criteria and randomized to either BP (n = 71) or EP (n = 76) treatment arms. A non-inferior response rate (RR) in the BP arm, analyzed by intent-to-treat analysis according to Response Evaluation Criteria in Solid Tumors version 1.0 criteria, was used as the primary endpoint. The secondary endpoints were progression-free survival (PFS) and overall survival (OS).ResultsIn the BP arm, one patient had a complete response, 41 had a partial response (PR), and 17 had stable disease (SD). In the EP arm, 35 patients had PR and 28 had SD. The RR in the BP arm was non-inferior to the EP regimen in patients with ES-SCLC (BP: 59.2 %, EP: 46.1 %, difference: 13.1 %, 90 % two-sided confidence interval: -0.3-26.5, meeting the predefined non-inferiority criterion of -15.0 %). No significant differences in OS or PFS were observed between the treatment arms. Hematologic toxicities, including grade 3/4 anemia and thrombocytopenia, were significantly more prevalent in the BP arm than the EP arm.ConclusionsThe RR to the BP regimen was non-inferior to the EP regimen in chemotherapy- and radiotherapy-naïve patients with previously untreated ES-SCLC. Hematologic toxicities were significantly more prevalent in the BP group, indicating that BP should be used with care, particularly in patients with a poor performance status. Further studies assessing PFS and OS are required to validate the superiority of the BP regimen.Trial registrationClinicalTrials.gov identifier NCT00826644 . Date of Registration: January 21, 2009.