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Phase III randomized trial of weekly cisplatin and irradiation versus cisplatin and tirapazamine and irradiation in stages IB2, IIA, IIB, IIIB, and IVA cervical carcinoma limited to the pelvis: a Gynecologic Oncology Group study.

ABSTRACT: This prospective, randomized phase III intergroup trial of the Gynecologic Oncology Group and National Cancer Institute of Canada Clinical Trials Group was designed to test the effectiveness and safety of adding the hypoxic cell sensitizer tirapazamine (TPZ) to standard cisplatin (CIS) chemoradiotherapy in locally advanced cervix cancer.Patients with locally advanced cervix cancer were randomly assigned to CIS chemoradiotherapy versus CIS/TPZ chemoradiotherapy. Primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and tolerability.PFS was evaluable in 387 of 402 patients randomly assigned over 36 months, with enrollment ending in September 2009. Because of the lack of TPZ supply, the study did not reach its original target accrual goal. At median follow-up of 28.3 months, PFS and OS were similar in both arms. Three-year PFS for the TPZ/CIS/RT and CIS/RT arms were 63.0% and 64.4%, respectively (log-rank P = .7869). Three-year OS for the TPZ/CIS/RT and CIS/RT arms were 70.5% and 70.6%, respectively (log-rank P = .8333). A scheduled interim safety analysis led to a reduction in the starting dose for the TPZ/CIS arm, with resulting tolerance in both treatment arms.TPZ/CIS chemoradiotherapy was not superior to CIS chemoradiotherapy in either PFS or OS, although definitive commentary was limited by an inadequate number of events (progression or death). TPZ/CIS chemoradiotherapy was tolerable at a modified starting dose.

SUBMITTER: DiSilvestro PA

PROVIDER: S-EPMC3912330 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Phase III randomized trial of weekly cisplatin and irradiation versus cisplatin and tirapazamine and irradiation in stages IB2, IIA, IIB, IIIB, and IVA cervical carcinoma limited to the pelvis: a Gynecologic Oncology Group study.

DiSilvestro Paul A PA Ali Shamshad S Craighead Peter S PS Lucci Joseph A JA Lee Yi-Chun YC Cohn David E DE Spirtos Nicola M NM Tewari Krishnasu S KS Muller Carolyn C Gajewski Walter H WH Steinhoff Margaret M MM Monk Bradley J BJ

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20140106 5

<h4>Purpose</h4>This prospective, randomized phase III intergroup trial of the Gynecologic Oncology Group and National Cancer Institute of Canada Clinical Trials Group was designed to test the effectiveness and safety of adding the hypoxic cell sensitizer tirapazamine (TPZ) to standard cisplatin (CIS) chemoradiotherapy in locally advanced cervix cancer.<h4>Patients and methods</h4>Patients with locally advanced cervix cancer were randomly assigned to CIS chemoradiotherapy versus CIS/TPZ chemorad ...[more]

PMID: 24395863

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Project description:BackgroundDespite screening campaigns, cervical cancers remain among the most prevalent malignancies and carry significant mortality, especially in developing countries. Most studies report outcomes of patients receiving the usual standard of care. It is possible that these selected patients may not correctly represent patients in a real-world setting, which may be a limitation in interpreting outcomes. This study was undertaken to identify prognostic factors, management strategies and outcomes of locally advanced cervical cancers (LACC) treated in daily clinical practice.MethodsMedical files of all consecutive patients treated with curative intent for LACC in a French Cancer Care Center between 2004 and 2014 were reviewed retrospectively.ResultsNinety-four patients were identified. Performance status was ≥ 2 in 10.6%. Median age at diagnosis was 63.0. Based on the International Federation of Gynecology and Obstetrics classification, tumours were classified as follows: 10.6% IB2, 22.3% IIA, 51.0% IIB, 4.3% IIIA and 11.7% IIIB. Pelvic lymph nodes were involved in 34.0% of cases. Radiotherapy was delivered for all patients. Radiotherapy technique was intensity modulated radiation therapy or volumetric modulated arc therapy in 39.4% of cases. A concurrent cisplatin chemotherapy was delivered in 68.1% of patients. Brachytherapy was performed in 77.7% of cases. The recommended standard care (concurrent chemoradiotherapy with at least five chemotherapy cycles during radiotherapy, followed by brachytherapy) was delivered in 43.6%. The median overall treatment time was 56 days. Complete tumour sterilisation was achieved in 55.2% of cases. Mean follow-up was 54.3 months. Local recurrence rate was 18.1%. Five-year overall survival was 61.9% (95% Confident Interval (CI) = 52.3-73.2) and five-year disease-specific survival was 68.5% (95% CI = 59.2-79.2). Poor performance status, lymph nodes metastasis and absence of concurrent chemotherapy were identified as poor prognostic factors in multivariate analysis.ConclusionsLess than 50% of patients received the standard care. Because LACC patients and disease are heterogeneous, treatment tailoring appears to be common in current clinical practice. However, guidelines for tailoring management are not currently available. More data about real-world settings are required in order to to optimise clinical trials' aims and designs, and make them translatable in daily clinical practice.Trial registrationretrospectively registered.

Project description:BackgroundThis study was to compare the efficacy and safety between neoadjuvant chemotherapy followed by radical surgery (NACT+RS) and radiotherapy only (RT) or concurrent chemoradiotherapy (CCRT) for treatment of patients with stage IB2, IIA, or IIB cervical cancer.MethodThe electronic databases of PubMed, Embase, and the Cochrane Library were searched to screen relevant studies from their inception to October 2018. Clinical data including overall survival (OS), disease-free survival (DFS), and adverse events were extracted. Egger's test was used to evaluate the publication bias, and sensitivity analysis was conducted to estimate the robustness of results.ResultsFinally, three randomized controlled trials (RCTs) and two case-control studies consisting of 1,275 patients with stage IB2, IIA, or IIB cervical cancer were included in the current study. Overall, pooled results showed no significant differences in OS ((hazard ratio (HR) = 0.603, 95%CI = 0.350 - 1.038) and DFS (HR = 0.678, 95%CI = 0.242 - 1.904) for patients treated with NACT+RS compared with RT only or CCRT, but the subgroup analysis showed that the OS and DFS were significantly longer in the NACT+RS groups than the RT or CCRT group (OS: HR = 0.431, 95%CI = 0.238 - 0.781, p = 0.006; DFS: HR = 0.300, 95%CI = 0.187 - 0.482, p < 0.001) for the population with median follow-up time of more than 60 months. For adverse events, the incidence of thrombocytopenia in the NACT+RS group was significantly higher than that in the RT only or CCRT group (relative risk (RR) = 3.240, 95% CI 1.575-6.662), while the incidence of diarrhea was significantly lower than that in the RT only or CCRT group (RR = 0.452, 95% CI =0.230-0.890).ConclusionThese findings suggest that the short-term therapeutic effects of the two treatments may be possibly equal for patients with stage IB2-IIB cervical cancer, but the long-term effects for improving OS and DFS may be better using NACT+RS compared with the RT only or CCRT.

Project description:Background: The systemic immune-inflammation index (SII) has been identified as a predictor of chemotherapy efficacy for a variety of cancers, and we aimed to determine its ability to predict the response to chemotherapy and its long-term prognosis for patients with cervical squamous cell carcinoma (CSCC) who have underwent platinum-based neoadjuvant chemotherapy (NACT). Methods: The date from 210 patients (133 in the training cohort and 77 in the validation cohort) with CSCC who received NACT were analyzed retrospectively. The association between SII and the pathological complete response (pCR) was determined using Pearson's chi-square test, receiver operating characteristic (ROC) curve, and Logistic regression analysis. The Kaplan-Meier method and Cox proportional regression model were used to assess the relationship between SII and progression-free survival (PFS) or overall survival (OS). Results: The calculated optimal SII cutoff values for pCR and survival were 568.7051 and 600.5683, respectively, and patients were divided into two groups: a low SII group (≤568.7051 or ≤600.5683) and a high SII group (>568.7051 or >600.5683). A high SII was associated significantly with a lower pCR. Further analysis determined that SII was a more efficient predictor of pCR than the prognostic nutritional index, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio. Upon multivariate logistic analysis, SII proved to be an independent risk factor to predict the pCR of patients with CSCC. Kaplan-Meier analysis demonstrated that PFS and OS rates were significantly higher in the low-SII group compared with those in the high-SII group. Additional multivariate analysis indicated that the SII is an independent prognostic factor for patients with CSCC treated with NACT. Conclusion: The results confirmed that the pre-treatment SII is not only an independent predictor of pCR but also an independent prognostic factor of CSCC patients treated with platinum based NACT.

Dataset Information

Phase III randomized trial of weekly cisplatin and irradiation versus cisplatin and tirapazamine and irradiation in stages IB2, IIA, IIB, IIIB, and IVA cervical carcinoma limited to the pelvis: a Gynecologic Oncology Group study.

Publications

Phase III randomized trial of weekly cisplatin and irradiation versus cisplatin and tirapazamine and irradiation in stages IB2, IIA, IIB, IIIB, and IVA cervical carcinoma limited to the pelvis: a Gynecologic Oncology Group study.

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