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Long-Term Disease Control with Triapine-Based Radiochemotherapy for Patients with Stage IB2-IIIB Cervical Cancer.

ABSTRACT: BACKGROUND:National Cancer Institute phase I #7336 and phase II #8327 clinical trials explored the safety and efficacy of triapine (NSC #663249) added to cisplatin radiochemotherapy in untreated patients with advanced-stage cervical cancer. Triapine inhibits ribonucleotide reductase, the rate-limiting enzyme responsible for DNA-building deoxyribonucleotides, and thereby, enhances radiochemosensitivity by prolonging DNA repair time. Here, we report 3-year efficacy endpoints of pelvic locoregional relapse rate, disease-free, and overall survivals. METHODS:Eligible patients with bulky IB-IIIB cervical cancer underwent three-times weekly triapine (25 or 50?mg/m(2)), once-weekly cisplatin (40?mg/m(2)), and conventional daily pelvic radiation followed by brachytherapy. A cumulative incidence method estimated pelvic locoregional relapse rates. Disease-free survival was measured from radiochemotherapy start date to the date of first relapse or cancer-related death. Overall survival was measured from radiochemotherapy start date to the date of any-cause death. The Kaplan-Meier method estimated survivals. FINDINGS:Between 2006 and 2011, 24 untreated patients with cervical cancer met criteria for reporting in this study. A median 3.4?years of follow-up time (range, 0.3-7.6?years) has been observed. All had squamous cancers and the majority had either node-positive stage IB-IIA (33%) or stage IIIB (42%) disease. The 3-year pelvic locoregional relapse rate, disease-free survival, and overall survival were 4% [95% confidence interval (CI), 0-20%], 80% (95% CI: 71-89%), and 82% (95% CI: 74-90%), respectively. INTERPRETATION:Triapine radiochemotherapy was safe, active, and effective in patients with untreated advanced-stage cervical cancer, worthy of randomized clinical trial study.

SUBMITTER: Kunos CA

PROVIDER: S-EPMC4109518 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Long-Term Disease Control with Triapine-Based Radiochemotherapy for Patients with Stage IB2-IIIB Cervical Cancer.

Kunos Charles A CA Sherertz Tracy M TM

Frontiers in oncology 20140724

<h4>Background</h4>National Cancer Institute phase I #7336 and phase II #8327 clinical trials explored the safety and efficacy of triapine (NSC #663249) added to cisplatin radiochemotherapy in untreated patients with advanced-stage cervical cancer. Triapine inhibits ribonucleotide reductase, the rate-limiting enzyme responsible for DNA-building deoxyribonucleotides, and thereby, enhances radiochemosensitivity by prolonging DNA repair time. Here, we report 3-year efficacy endpoints of pelvic loco ...[more]

PMID: 25105092

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Project description:Despite 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.Medical files of all consecutive patients treated with curative intent for LACC in a French Cancer Care Center between 2004 and 2014 were reviewed retrospectively.Ninety-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.Less 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.retrospectively registered.

Project description:BackgroundCervical cancer is the fourth most common cancer in women, with 528,000 estimated new cases globally in 2012. A large majority (around 85%) of the disease burden occurs in low- and middle-income countries (LMICs), where it accounts for almost 12% of all female cancers. Treatment of stage IB2 cervical cancers, which sit between early and advanced disease, is controversial. Some centres prefer to treat these cancers by radical hysterectomy, with chemoradiotherapy reserved for those at high risk of recurrence. In the UK, we treat stage IB2 cervical cancers mainly with chemoradiotherapy, based on the rationale that a high percentage will have risk factors necessitating chemoradiotherapy postsurgery. There has been no systematic review to determine the best possible evidence in managing these cancers.ObjectivesTo determine if primary surgery for stage IB2 cervical cancer (type II or type III radical hysterectomy with lymphadenectomy) improves survival compared to primary chemoradiotherapy.To determine if primary surgery combined with postoperative adjuvant chemoradiotherapy, for stage IB2 cervical cancer increases patient morbidity in the management of stage IB2 cervical cancer compared to primary chemoradiotherapy.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 3), MEDLINE via Ovid (1946 to April week 2, 2018) and Embase via Ovid (1980 to 2018 week 16). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies up to April 2018.Selection criteriaWe searched for randomised controlled trials (RCTs), quasi-RCTs or non-randomised studies (NRSs) comparing surgery to chemoradiotherapy in stage IB2 cervical cancers.Data collection and analysisTwo review authors independently assessed whether potentially relevant studies met the inclusion criteria, abstracted data, assessed risk of bias and analysed data using standard methodological procedures expected by Cochrane.Main resultsWe identified 4968 records from the literature searches, but we did not identify any RCTs that compared primary surgery with chemoradiotherapy in stage IB2 cervical cancer.We found one NRS comparing surgery to chemoradiotherapy in IB2 and IIA2 cervical cancers which met the inclusion criteria. However, we were unable to obtain data for stage IB2 cancers only and considered the findings very uncertain due to a high risk of selection bias.Authors' conclusionsThere is an absence of high-certainty evidence on the relative benefits and harms of primary radical hysterectomy versus primary chemoradiotherapy for stage IB2 cervical cancer. More research is needed on the different treatment options in stage IB2 cervical cancer, particularly with respect to survival, adverse effects, and quality of life to facilitate informed decision-making and individualised care.

Dataset Information

Long-Term Disease Control with Triapine-Based Radiochemotherapy for Patients with Stage IB2-IIIB Cervical Cancer.

Publications

Long-Term Disease Control with Triapine-Based Radiochemotherapy for Patients with Stage IB2-IIIB Cervical Cancer.

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