Highlights
- •Paclitaxel–carboplatin and bevacizumab therapy is a tolerable treatment for advanced or recurrent cervical cancer.
- •A history of radiation therapy is a risk of fistula and perforation.
- •Bevacizumab maintenance therapy for advanced and recurrent cervical cancer is considered safe and may be effective.
Abstract
Objective
This multicenter, open-label, phase II study aimed to evaluate the efficacy and safety
of paclitaxel–carboplatin, bevacizumab, and bevacizumab-based maintenance therapy
for metastatic, recurrent, and persistent uterine cervical cancer.
Methods
Patients with measurable diseases that were not adapted to regional therapies, such
as surgery or radiotherapy, and were systematic chemotherapy-naïve were eligible.
The participants received paclitaxel (175 mg/m2), carboplatin (AUC 5), and bevacizumab (15 mg/m2) every three weeks until disease progression or unacceptable adverse events occurred.
The primary endpoint was progression-free survival (PFS). The secondary endpoints
were overall response rate (ORR), overall survival (OS), safety, and time to treatment
failure.
Results
Sixty-nine patients were analyzed using our protocol. The median paclitaxel– carboplatin
therapy duration was six cycles; 40% of patients received bevacizumab maintenance
therapy. The median PFS was 11.3 months. The median OS was not reached; the median
time to treatment failure was 5.9 months. The ORR was 79.7% [95% confidence interval
(CI) 63.8–88.4]; 16 patients (23.2%) showed complete response (CR) and 39 patients
(56.5%) showed partial response (PR). The median PFS was 14.3 months (95% CI 7.3–17
months) for the 25 patients who received maintenance therapy and 7.4 months (95% CI
6.1–11 months) for nonrecipients (p = 0.0449). Gastrointestinal perforation/fistulas occurred in four patients (5.6%),
all of whom had a history of radiation therapy.
Conclusions
Paclitaxel–carboplatin and bevacizumab therapy is an acceptable and tolerable treatment
for advanced or recurrent cervical cancer.
Keywords
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References
- Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study.J. Clin. Oncol. 2009; 27: 4649-4655https://doi.org/10.1200/JCO.2009.21.8909
- A randomized, phase III trial of paclitaxel plus carboplatin (TC) versus paclitaxel plus cisplatin (TP) in stage IVb, persistent or recurrent cervical cancer: Japan Clinical Oncology Group study (JCOG0505).J. Clin. Oncol. 2012; 30: 2129-2135https://doi.org/10.1200/jco.2012.30.15_suppl.5006
- A systematic review comparing cisplatin and carboplatin plus paclitaxel-based chemotherapy for recurrent or metastatic cervical cancer.Gynecol. Oncol. 2014; 133: 117-123https://doi.org/10.1016/j.ygyno.2014.01.042
- Improved survival with bevacizumab in advanced cervical cancer.N. Engl. J. Med. 2014; 370: 734-743https://doi.org/10.1056/NEJMoa1309748
- Bevacizumab for advanced cervical cancer: patient-reported outcomes of a randomised, phase 3 trial (NRG Oncology-Gynecologic Oncology Group protocol 240).Lancet Oncol. 2015; 16: 301-311https://doi.org/10.1016/S1470-2045(15)70004-5
- Bevacizumab for advanced cervical cancer: final overall survival and adverse analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240).Lancet. 2017; 390: 1654-1663https://doi.org/10.1016/S0140-6736(17)31607-0
- Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study.J. Clin. Oncol. 2009; 27: 1069-1074https://doi.org/10.1200/JCO.2008.18.9043
- Primary results from CECILIA, a global single-arm phase II study evaluating bevacizumab, carboplatin and paclitaxel for advanced cervical cancer.Gynecol. Oncol. 2020; 159: 142-149https://doi.org/10.1016/j.ygyno.2020.07.026
- Oncogenes and tumor angiogenesis: the HPV-16 E6 oncoprotein activates the vascular endothelial growth factor (VEGF) gene promoter in a p53 independent manner.Oncogene. 2000; 19: 4611-4620https://doi.org/10.1038/sj.onc.1203817
- Vascular endothelial growth factor (VEGF) expression is a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix.Br. J. Cancer. 2000; 83: 620-625https://doi.org/10.1054/bjoc.2000.1319
- Vascular endothelial growth factor and prognosis of cervical carcinoma.Obstet. Gynecol. 2000; 96: 721-726https://doi.org/10.1016/s0029-7844(00)01025-5
- Systematic review and network meta-analysis of bevacizumab plus first-line topotecan-paclitaxel or cisplatin-paclitaxel versus non-bevacizumab-containing therapies in persistent, recurrent, or metastatic cervical cancer.Int. J. Gynecol. Cancer. 2017; 27: 1237-1246https://doi.org/10.1097/IGC.0000000000001000
- Vascular normalization as an emerging strategy to enhance cancer immunotherapy.Cancer Res. 2013; 73: 2943-2948https://doi.org/10.1158/0008-5472.CAN-12-4354
- Maintenance treatment with bevacizumab prolongs survival in an in vivo ovarian cancer model.Clin. Cancer Res. 2008; 14: 7781-7789https://doi.org/10.1158/1078-0432.CCR-08-0243
- ICON7 investigators, a phase 3 trial of bevacizumab in ovarian cancer.N. Engl. J. Med. 2011; 365: 2484-2496https://doi.org/10.1056/NEJMoa1103799
- OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer.J. Clin. Oncol. 2012; 30: 2039-2045https://doi.org/10.1200/JCO.2012.42.0505
- Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial.Lancet Oncol. 2017; 18: 779-791https://doi.org/10.1016/S1470-2045(17)30279-6
- Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the Aurelia open-label randomized phase III trial.J. Clin. Oncol. 2014; 32: 1302-1308https://doi.org/10.1200/JCO.2013.51.4489
- Hypoalbuminemia is a predictive factor for fistula formation in recurrent cervical cancer.Am. J. Clin. Oncol. 2018; 41: 933-937https://doi.org/10.1097/COC.0000000000000403
- Incorporation of whole pelvic radiation into treatment of stage IVB cervical cancer: a novel treatment strategy.Gynecol. Oncol. 2020; 156: 100-106https://doi.org/10.1016/j.ygyno.2019.10.033
- Efficacy of radical doses of pelvic radiotherapy for primary tumor treatment in patients with newly diagnosed organ metastatic cervical cancer.Radiat. Oncol. 2019; 14: 82https://doi.org/10.1186/s13014-019-1297-x
- Definitive local therapy is associated with improved overall survival in metastatic cervical cancer.Pract. Radiat. Oncol. 2018; 8: e377-e385https://doi.org/10.1016/j.prro.2018.05.010
- Pembrolizumab for persistent, recurrent, or metastatic cervical cancer.N. Engl. J. Med. 2021; 385: 1856-1867https://doi.org/10.1056/NEJMoa2112435
- A randomized phase III trial of platinum chemotherapy plus paclitaxel with bevacizumab and atezolizumab versus platinum chemotherapy plus paclitaxel and bevacizumab in metastatic (stage IVB), persistent, or recurrent carcinoma of the cervix: the BEATcc study (ENGOT-Cx10/GEICO 68-C/JGOG1084/GOG-3030).Int. J. Gynecol. Cancer. 2020; 30: 139-143https://doi.org/10.1136/ijgc-2019-000880
Article info
Publication history
Published online: April 26, 2022
Accepted:
April 15,
2022
Received in revised form:
April 15,
2022
Received:
December 28,
2021
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
