Pathologic response and toxicity assessment of chemoradiotherapy with cisplatin versus cisplatin plus gemcitabine in cervical cancer: A randomized Phase II study

Dueñas‐González, Alfonso; Cetina, Lucely; López-Graniel, C.; González-Enciso, Aarón; Gómez-Gonzalez, Ernesto; Rivera-Rubí, Lesbia María; Montalvo-Esquivel, Gonzalo; Muñoz-González, David Eduardo; Robles-Flores, Juan Ubaldo; Vazquez-Govea, Elisa; Garza, Jaime de la; Mohar, Alejandro

doi:10.1016/j.ijrobp.2004.07.676

Cited by 71 publications

(49 citation statements)

References 28 publications

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“…[17][18][19] In these trials, gemcitabine was given after cisplatin, as in the current trial. Likewise, two Phase II studies from Mexico 17 and Honduras 18 utilized gemcitabine (125 mg/m 2 ) given after cisplatin at 40 mg/m 2 with moderate toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…16 There were previous Phase II trials using weekly gemcitabine at a dose of 125 mg/m 2 with cisplatin at a dose of 40 mg/m 2 given concurrently with primary pelvic radiotherapy. [17][18][19] We adopted this dosage for use in a randomized clinical trial (RCT) in Thai women as it may be more effective than single weekly cisplatin and less expensive than single weekly gemcitabine. The overall compliance and side effects were monitored periodically, and any unacceptable adverse effects were reported.…”

Section: Introductionmentioning

confidence: 99%

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Weekly gemcitabine and cisplatin concurrent with pelvic irradiation for primary therapy of cervical cancer: report of the first seven cases in Thai women

et al. 2007

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Weekly gemcitabine and cisplatin concurrent with pelvic irradiation for primary therapy of cervical cancer: report of the first seven cases in Thai women

et al. 2007

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“…However, acute and late toxicity are significant problems, and the incidence of locoregional failure, distant metastasis, and cancer mortality, especially for stage IIB-IVA disease, remain high (6). Furthermore, despite evidence that intensifying concurrent chemotherapy improves survival (7)(8)(9), high rates of gastrointestinal (GI) and hematologic toxicity have limited the adoption of such strategies. Therefore, innovations to reduce toxicity and barriers to treatment intensification are needed to improve the therapeutic ratio of CRT.…”

Section: Introductionmentioning

confidence: 99%

Phase 2 Multicenter Clinical Trial of Bone Marrow–Sparing Intensity Modulated Radiation Therapy With Concurrent Cisplatin for Stage IB-IVA Cervical Cancer

Mell

Sirák

et al. 2016

International Journal of Radiation Oncology*Biology*Physics

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SummaryWe performed an international phase II trial to test the Purpose: To test the hypothesis that intensity modulated radiation therapy (IMRT) reduces acute hematologic and gastrointestinal (GI) toxicity for patients with locoregionally advanced cervical cancer. hypothesis that intensity modulated radiation therapy (IMRT) would reduce the acute toxicity for locoregionally advanced cervical cancer. For the 83 patients enrolled, acute gastrointestinal toxicity was significantly reduced with both IMRT and positron emission tomography-guided bone marrow sparing IMRT (IG-IMRT) compared with historical controls. The incidence of neutropenia was significantly reduced in patients who underwent IG-IMRT. We conclude that IMRT reduces acute toxicity compared with standard treatment in this population and that IG-IMRT warrants testing in randomized trials.Methods and Materials: We enrolled patients with stage IB-IVA cervical carcinoma in a single-arm phase II trial involving 8 centers internationally. All patients received weekly cisplatin concurrently with once-daily IMRT, followed by intracavitary brachytherapy, as indicated. The primary endpoint was the occurrence of either acute grade !3 neutropenia or clinically significant GI toxicity within 30 days of completing chemoradiation therapy. A preplanned subgroup analysis tested the hypothesis that positron emission tomography-based image-guided IMRT (IG-IMRT) would lower the risk of acute neutropenia. We also longitudinally assessed patients' changes in quality of life. Results: From October 2011 to April 2015, 83 patients met the eligibility criteria and initiated protocol therapy. The median follow-up was 26.0 months. The incidence of any primary event was 26.5% (95% confidence interval [CI] 18.2%-36.9%), significantly lower than the 40% incidence hypothesized a priori from historical data (PZ.012). The incidence of grade !3 neutropenia and clinically significant GI toxicity was 19.3% (95% CI 12.2%-29.0%) and 12.0% (95% CI 6.7%-20.8%), respectively. Compared with patients treated without IG-IMRT (nZ48), those treated with IG-IMRT (nZ35) had a significantly lower incidence of grade !3 neutropenia (8.6% vs 27.1%; 2-sided c 2 PZ.035) and nonsignificantly lower incidence of grade !3 leukopenia (25.7% vs 41.7%; PZ.13) and any grade !3 hematologic toxicity (31.4% vs 43.8%; PZ.25). Conclusions: IMRT reduces acute hematologic and GI toxicity compared with standard treatment, with promising therapeutic outcomes. Positron emission tomography IG-IMRT reduces the incidence of acute neutropenia. Ó

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“…Nonetheless, outcomes for patients with advanced disease are still sub-optimal, suggesting that treatment could be intensified for some patients. Preliminary clinical studies of combination chemotherapy given concurrently with RT have demonstrated promising disease control; however, the high rate of HT is a limiting factor (27)(28)(29)(30). Finally, limiting CRT-associated BM injury incurred during definitive therapy may improve tolerance to subsequent chemotherapy given in the adjuvant or recurrent/metastatic setting.…”

Section: Discussionmentioning

confidence: 99%

Normal Tissue Complication Probability Modeling of Acute Hematologic Toxicity in Cervical Cancer Patients Treated With Chemoradiotherapy

Rose

Aydogan

Yeginer

et al. 2009

International Journal of Radiation Oncology*Biology*Physics

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PURPOSE-To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy (CRT), and to develop a normal tissue complication probability (NTCP) model for HT.METHODS AND MATERIALS-We tested associations between hematologic nadirs during CRT and the volume of BM receiving ≥ 10 and 20 Gy (V 10 and V 20 ) using a previously developed linear regression model. The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic radiotherapy. Subsequently, these data were pooled with 37 identically treated patients from a prior study, forming a cohort of 81 patients for NTCP analysis. Generalized linear modeling was used to test associations between hematologic nadirs and dosimetric parameters, adjusting for body mass index. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints.RESULTS-In the validation cohort, significant negative correlations were observed between white blood cell count (WBC) nadir and V 10 (regression coefficient (β)=−0.060, p=0.009) and V 20 (β=−0.044, p=0.010). In the combined cohort, the (adjusted) β estimates for log(WBC) vs. V 10 and V 20 were: −0.022 (p=0.025) and −0.021 (p=0.002), respectively. Patients with V 10 ≥ 95% were more likely to experience grade ≥ 3 leukopenia (68.8% vs. 24.6%, p<0.001) as were patients with V 20 > 76% (57.7% vs. 21.8%, p=0.001). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conflicts of Interests:NonePresented at the 51st meeting of the American Society of Radiation Oncology, Chicago, IL, 2009 NIH Public Access CONCLUSIONS-These findings support the hypothesis that HT increases with increasing pelvic BM volume irradiated. Efforts to maintain V 10 < 95% and V 20 < 76% may reduce HT.

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Pathologic response and toxicity assessment of chemoradiotherapy with cisplatin versus cisplatin plus gemcitabine in cervical cancer: A randomized Phase II study

Cited by 71 publications

References 28 publications

Weekly gemcitabine and cisplatin concurrent with pelvic irradiation for primary therapy of cervical cancer: report of the first seven cases in Thai women

Weekly gemcitabine and cisplatin concurrent with pelvic irradiation for primary therapy of cervical cancer: report of the first seven cases in Thai women

Phase 2 Multicenter Clinical Trial of Bone Marrow–Sparing Intensity Modulated Radiation Therapy With Concurrent Cisplatin for Stage IB-IVA Cervical Cancer

Normal Tissue Complication Probability Modeling of Acute Hematologic Toxicity in Cervical Cancer Patients Treated With Chemoradiotherapy

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