Phase III, Open-Label, Randomized Study Comparing Concurrent Gemcitabine Plus Cisplatin and Radiation Followed by Adjuvant Gemcitabine and Cisplatin Versus Concurrent Cisplatin and Radiation in Patients With Stage IIB to IVA Carcinoma of the Cervix

Mahidol University, Krung Thep, Bangkok, Thailand
Journal of Clinical Oncology (Impact Factor: 18.43). 03/2011; 29(13):1678-85. DOI: 10.1200/JCO.2009.25.9663
Source: PubMed


To determine whether addition of gemcitabine to concurrent cisplatin chemoradiotherapy and as adjuvant chemotherapy with cisplatin improves progression-free survival (PFS) at 3 years compared with current standard of care in locally advanced cervical cancer.
Eligible chemotherapy- and radiotherapy-naive patients with stage IIB to IVA disease and Karnofsky performance score ≥ 70 were randomly assigned to arm A (cisplatin 40 mg/m(2) and gemcitabine 125 mg/m(2) weekly for 6 weeks with concurrent external-beam radiotherapy [XRT] 50.4 Gy in 28 fractions, followed by brachytherapy [BCT] 30 to 35 Gy in 96 hours, and then two adjuvant 21-day cycles of cisplatin, 50 mg/m(2) on day 1, plus gemcitabine, 1,000 mg/m(2) on days 1 and 8) or to arm B (cisplatin and concurrent XRT followed by BCT only; dosing same as for arm A).
Between May 2002 and March 2004, 515 patients were enrolled (arm A, n = 259; arm B, n = 256). PFS at 3 years was significantly improved in arm A versus arm B (74.4% v 65.0%, respectively; P = .029), as were overall PFS (log-rank P = .0227; hazard ratio [HR], 0.68; 95% CI, 0.49 to 0.95), overall survival (log-rank P = .0224; HR, 0.68; 95% CI, 0.49 to 0.95), and time to progressive disease (log-rank P = .0012; HR, 0.54; 95% CI, 0.37 to 0.79). Grade 3 and 4 toxicities were more frequent in arm A than in arm B (86.5% v 46.3%, respectively; P < .001), including two deaths possibly related to treatment toxicity in arm A.
Gemcitabine plus cisplatin chemoradiotherapy followed by BCT and adjuvant gemcitabine/cisplatin chemotherapy improved survival outcomes with increased but clinically manageable toxicity when compared with standard treatment.

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    • "Dans la série de l'institut Gustave-Roussy, deux tiers des patientes en situation de rechute étaient atteintes de métastases, dans la moitié des cas isolées, ce qui soulève la nécessité de traitements systémiques plus agressifs [19]. Une des voies de recherche consiste à intensifier la chimiothérapie concomitante , avec de la gemcitabine, du cétuximab (essai de phase II cétuxicol) ou d'adjonction d'un agent antiviral (essai de phase I HPV-RX) [21]. Une autre voie, est l'adjonction d'une chimiothérapie adjuvante. "
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    ABSTRACT: Intensity modulated radiation therapy has demonstrated its ability to prevent xerostomia in the treatment of head and neck cancers, as well as post-radiation related proctitis in prostate cancer. In the management of cervical carcinomas, many published dosimetric studies have shown its ability to limit the irradiation of organs at risk. However, clinical data remain limited to comparisons of cohorts, mostly retrospective, but promising. This review aims to update the current state of knowledge. © 2014 Société française de radiothérapie oncologique (SFRO).
    Cancer/Radiothérapie 01/2014; 18(2). DOI:10.1016/j.canrad.2013.11.012 · 1.41 Impact Factor
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    • "The 3-year RFS and OS rates were estimated to be 67% and 72%, respectively [34]. These encouraging results led to a large randomized, phase III trial [33] (Table 1) designed to determine whether the addition of gemcitabine to concurrent cisplatin chemoradiotherapy could improve outcome compared with current standard of care in locally advanced cervical cancer: five hundred and fifteen patients with stage IIB-IVA disease were randomly assigned to either cisplatin and gemcitabine, weekly for 6 weeks with concurrent external-beam radiotherapy, followed by brachytherapy and then two adjuvant cycles of cisplatin plus gemcitabine, (arm A) or to cisplatin and concurrent radiotherapy followed by brachytherapy only at the same doses (arm B). PFS at 3 years was significantly improved in arm A versus arm B (74.4% versus 65.0%, resp.; P = 0.029) as were overall PFS (hazard ratio (HR) = 0.68; 95% CI, 0.49 to 0.95; P = 0.0227) and OS (HR = 0.68; 95% CI, 0.49 to 0.95; P = 0.0224). "
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    Obstetrics and Gynecology International 05/2013; 2013(5):536765. DOI:10.1155/2013/536765
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    • "We have to consider advanced stage or pelvic LN positive cases as systemic disease, rather than locally advanced cancer. Adjuvant chemotherapy after CCRT may improve the outcome of advanced cancer with extra pelvic disease [18,19]. "
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    ABSTRACT: To evaluate the clinical efficacy of concurrent chemoradiotherapy (CCRT) using daily low-dose cisplatin for cervical cancer. Fifty-one patients with locally advanced cervical cancer (FIGO stage IB2, bulky IIA, IIB-IVA) who were treated with CCRT as primary therapy at Kurume University Hospital between 2000 and 2007 were retrospectively reviewed. CCRT consisted of 5 mg/m(2)/day of cisplatin 5 days per week, and external beam radiotherapy (EBRT) administrated to whole pelvis to 45-50.6 Gy. High-dose-rate intracavitary brachytherapy was delivered in a single dose of 4-5 Gy at point A, once a week after 20-30 Gy of EBRT. The median follow-up duration was 42 months (range, 5 to 116 months). The overall response rate was 94.1%. Five year overall survival rate was 71.5% and 46.2% in stage I or II, and stage III or IVA, respectively. During follow-up period, 30 recurrences (58.8%) were found, the local failure rate was 39%, and distant failure rate was 35.2%, and both (local and distant) were 15.7%. Hematological toxicities were the most frequent acute toxicities. Grade 3 and 4 neutropenia was observed in 37.3%. Late intestinal toxicities appeared in 7 cases (13.7%), which occurred between 6 and 114 months after treatment. Four cases required bowel surgery. CCRT using daily low-dose cisplatin was tolerable and showed favorable initial response as the primary therapy for locally advanced uterine cervical cancer. But there was no remarkable long-term benefit for patients' survival or local disease control in this study. The incidence of late intestinal toxicity still requires further investigation.
    Journal of Gynecologic Oncology 04/2013; 24(2):108-13. DOI:10.3802/jgo.2013.24.2.108 · 2.49 Impact Factor
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