Impact of the Addition of Concurrent Chemotherapy to Pelvic Radiotherapy in Surgically Treated Stage IB1-IIB Cervical Cancer Patients With Intermediate-Risk or High-Risk Factors: A 13-Year Experience

Okazawa, Makoto; Mabuchi, Seiji; Isohashi, Fumiaki; Сузукі, Осаму; Yoshioka, Yasuo; Sasano, Tomoyuki; Ohta, Yukinobu; Kamiura, Shoji; Ogawa, Kazuhiko; Kimura, Tadashi

doi:10.1097/igc.0b013e31828703fd

Cited by 52 publications

(35 citation statements)

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“…Of these, 30 patients in CCRT-group and 21 patients in RT-group were included in our previous clinical studies [2127]. At our institutions, nedaplatin is employed as a radiosensitizing agent for patients with cervical cancer [2127282930]. In CCRT-group, weekly nedaplatin (40 mg/m 2 ) was administered intravenously during the course of pelvic radiotherapy.…”

Section: Methodsmentioning

confidence: 99%

Chemoradiotherapy followed by consolidation chemotherapy involving paclitaxel and carboplatin and in FIGO stage IIIB/IVA cervical cancer patients

et al. 2017

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ObjectiveTo evaluate the efficacy and toxicity of paclitaxel plus carboplatin (TC)-based concurrent chemoradiotherapy (CCRT) followed by consolidation chemotherapy in the International Federation of Gynecology and Obstetrics (FIGO) stage IIIB/IVA cervical cancer patients.MethodsWe reviewed the medical records of FIGO stage IIIB/IVA cervical cancer patients (n=30) who had been intended to be treated with TC-based CCRT followed by consolidation chemotherapy (TC-CCRT-group) from April 2012–May 2016. Patients who had been treated with CCRT involving a single platinum agent (CCRT-group; n=52) or definitive radiotherapy alone (RT-group; n=74) from January 1997–September 2012 were also identified and used as historical controls. Survival was calculated using the Kaplan-Meier method and compared using the log-rank test.ResultsOf the 30 patients included in the TC-CCRT-group, 22 patients (73.3%) completed the planned TC-based CCRT. The most frequently observed acute grade 3/4 hematological toxicities were leukopenia and neutropenia, and diarrhea was the most common acute grade 3/4 non-hematological toxicity. After a median follow-up of 35 months, 9 patients (30.0%) had developed recurrent disease. The patients’ estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 67.9% and 90.8%, respectively. In comparisons with historical control groups, the survival outcomes of TC-CCRT-group was significantly superior to CCRT-group in terms of OS (p=0.011) and significantly superior to RT-group in terms of both PFS (p=0.009) and OS (p<0.001).ConclusionTC-based CCRT followed by consolidation chemotherapy is safe and effective. A randomized controlled study needs to be conducted to further evaluate the efficacy of this multimodal approach in this patient population.

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Section: Methodsmentioning

confidence: 99%

Chemoradiotherapy followed by consolidation chemotherapy involving paclitaxel and carboplatin and in FIGO stage IIIB/IVA cervical cancer patients

et al. 2017

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“…An early study reported that, in patients with LVSI and deep stromal invasion, the 3-year RFS (recurrence-free survival) of the concurrent chemoradiation group was significantly greater than that of the radiation group [ 16 ]. Some retrospective studies in recent years also have showed the benefit of adding chemotherapy to radiation in patients with intermediate-risk factors and the levels of all toxicities were acceptable [ 17 - 20 ]. A statistically significant difference was found in the 3-year RFS rate among the no further treatment, RT, and CCRT groups (67.5%, 90.5%, and 97.5%, respectively; p <0 .05) in the study of Ryu SY et al [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…A statistically significant difference was found in the 3-year RFS rate among the no further treatment, RT, and CCRT groups (67.5%, 90.5%, and 97.5%, respectively; p <0 .05) in the study of Ryu SY et al [ 18 ]. Okazawa M et al reviewed the medical records of 316 patients with stage IB1-IIB cervical cancer who had been treated with adjuvant radiotherapy (RT) (n = 124, RT group) or adjuvant CCRT (n = 192, CCRT group) after radical hysterectomy and found that CCRT was superior to RT with regard to recurrence rate and PFS in patents with 2 or more intermediate risk factors, while the patients with only 1 intermediate risk factor showed no survival benefit of CCRT over RT [ 20 ]. However, due to the lack of randomized trials, the benefit of concurrent chemoradiation over radiation in cervical cancer patients with intermediate-risk factors remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, the major toxicities of combined chemotherapy were bone marrow depression, mild to moderate gastrointestinal troubles, mild to moderate nephrotoxicities, total alopecia (in etoposide-cisplatin group), relatively low incidence of neurotoxicities and hepatotoxicities, rare incidence of pulmonary and cardiac toxicities and some reported secondary malignancies (acute leukemia and some solid tumors). In previous studies the levels of all these toxicities of combined chemotherapy were acceptable and most are reversible and transient [ 17 - 20 ]. Nevertheless, the results of the present study found that hematologic toxicity was significantly more frequent and more severe in the CCRT and CCRT + CT arms compared with the RT arm.…”

Section: Discussionmentioning

confidence: 99%

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Randomized phase III trial of radiotherapy or chemoradiotherapy with topotecan and cisplatin in intermediate-risk cervical cancer patients after radical hysterectomy

et al. 2015

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BackgroundIn cervical cancer patients with intermediate-risk factors, the optimal adjuvant therapy is still controversial. We undertook a randomized trial (ClinicalTrials.gov Identifier: NCT01418859) to compare the efficacy and toxicity of concurrent chemoradiotherapy with topotecan and cisplatin with radiotherapy alone in intermediate-risk cervical cancer patients.MethodsEligible patients were randomly assigned to one of three treatment arms including arm A (radiotherapy only,RT), arm B(concurrent chemoradiotherapy only, CCRT), and arm C (concurrent chemoradiotherapy with following consolidation chemotherapy, CCRT + CT). All eligible patients completed external RT (IMRT or 3D-CRT), receiving 45-50Gy /25f uniformly to the pelvis. Concurrent chemotherapy regimen was topotecan 0.75 mg/m2 for days 1, 2 and 3, followed by cisplatin 25 mg/m2 for days 1, 2 and 3. Three cycles of consolidation chemotherapy regimen was topotecan 1.5 mg/m2 for days 1 and 2, and 0.75 mg/m2 for day 3; followed by cisplatin 25 mg/m2 for days 1, 2 and 3, repeated every 21 days. Adverse events of each group were investigated and compared.ResultsThirty-nine patients enrolled onto the remaining regimens: 14 to RT, 15 to CCRT and 10 to CCRT + CT. Six patients (15.4%) did not complete the protocol treatment. Hematologic toxicity was more frequent and more severe in the CCRT and CCRT + CT arms compared with the RT arm. The incidence of grade 3-4 neutropenia was significantly different statistically between the RT, CCRT and CCRT + RT groups (15.4%, 46.7% and 100%, respectively; P = 0.002). Specially, three patients in CCRT + CT arm of all six patients who did not complete the protocol treatment discontinued planned therapy because of persistent grade 4 neutropenia. However, there were no significant differences in grade 3-4 non-hematologic toxicities between the three groups(all P > 0.05). Recurrence-free survival and overall survival of each group were not analyzed on account of a median follow-up of only 16 months.ConclusionsConcurrent chemoradiotherapy with topotecan and cisplatin showed severe hematologic toxicity in intermediate-risk cervical cancer patients after radical hysterectomy. Thus, the study was closed ahead of schedule.Trial registrationClinicalTrials.gov Identifier: NCT01418859.

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“…Since 1999, the treatment of cervical cancer has involved comprehensive treatment that combines surgery and radiotherapy with chemotherapy. Neoadjuvant chemotherapy reduces the gross tumor volume, extends the 5-year survival rate, and decreases the recurrence rate, and has thus attracted extensive attention for various studies (Hamed et al, 2012;Lai et al, 2013;Okazawa et al, 2013). However, the multidrug resistance (MDR) of tumor cells to chemotherapy influences the clinical application and efficacy of treatments.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of the reversal effect of mifepristone on drug resistance of the human cervical cancer cell line HeLa/MMC

Chen¹,

Duan²,

Zuo³

2014

Genet. Mol. Res.

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ABSTRACT. We examined the ability of mifepristone to reverse the in vitro drug resistance of human cervical cancer cells resistant to mitomycin-C (HeLa/MMC) cells and investigated the mechanism of this effect. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the drug resistance of HeLa/ MMC cells and the reversed drug resistance in vitro. Expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and glucosylceramide synthase (GCS) were measured in HeLa and HeLa/ MMC cells. The resistance index of HeLa/MMC cells on MMC was reduced from 5.02 to 1.46 after 10 mg/mL mifepristone exposure. A combination of mifepristone upregulated the Bax/Bcl-2 protein expression ratio and apoptosis in HeLa/MMC cells. GCS expression was significantly higher in HeLa/MMC cells than in HeLa cells (P < 0.01), but distinctly declined in both cell lines after mifepristone application (P < 0.01). Mifepristone reversed the resistance of HeLa/MMC cells to MMC in vitro; the overexpression of the GCS gene and the increased expression of apoptosis-related protein Bcl-2 may play important roles

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Impact of the Addition of Concurrent Chemotherapy to Pelvic Radiotherapy in Surgically Treated Stage IB1-IIB Cervical Cancer Patients With Intermediate-Risk or High-Risk Factors: A 13-Year Experience

Abstract: Postoperative CCRT improved the prognosis of FIGO stage IB1-IIB cervical cancer patients in the high-risk group and patients who displayed 2 or more intermediate-risk factors. Patients who displayed deep stromal invasion alone also derived clinical benefit from adjuvant treatment.

Cited by 52 publications

References 25 publications

Chemoradiotherapy followed by consolidation chemotherapy involving paclitaxel and carboplatin and in FIGO stage IIIB/IVA cervical cancer patients

Chemoradiotherapy followed by consolidation chemotherapy involving paclitaxel and carboplatin and in FIGO stage IIIB/IVA cervical cancer patients

Randomized phase III trial of radiotherapy or chemoradiotherapy with topotecan and cisplatin in intermediate-risk cervical cancer patients after radical hysterectomy

Mechanism of the reversal effect of mifepristone on drug resistance of the human cervical cancer cell line HeLa/MMC

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