Randomized Phase III Trial of Cisplatin With or Without Topotecan in Carcinoma of the Uterine Cervix: A Gynecologic Oncology Group Study

Long, Harry J.; Bundy, Brian N.; Grendys, Edward C.; Benda, Jo Ann; McMeekin, D. Scott; Sorosky, Joel I.; Miller, David S.; Eaton, Lynne; Fiorica, James V.

doi:10.1200/jco.2005.10.021

Cited by 498 publications

(377 citation statements)

References 19 publications

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“…The maximum tolerated daily dose was only 300mg/m 2 /bid [55]. A 3-weekly schedule of topotecan and cisplatin was shown to offer a modest but significant survival advantage compared to cisplatin alone when used to treat patients with metastatic disease, in the Gynecology Oncology Group (GOG) Trial 179 [56].…”

Section: Discussionmentioning

confidence: 99%

Concomitant and Neoadjuvant Chemotherapy for Cervical Cancer

Tierney¹,

Vale²,

Symonds³

2008

Clinical Oncology

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In the past, women with early stage cervical cancer have been treated with radical radiotherapy or radical surgery, and women with locally advanced disease with radical radiotherapy, each offering a good chance of cure. Numerous trials have investigated whether giving cytotoxic chemotherapy alongside radiotherapy or prior to local treatment could augment the established benefits of these therapies, and are reviewed here. There is a strong basis for the use of platinum-based chemoradiotherapy, the current standard of care, but little convincing evidence as to the therapeutic benefits of using concomitant hydroxyurea. Chemoradiotherapy based on other non-platinum agents may offer alternatives. The effect of chemoradiotherapy appears to vary according to the stage of disease, but all types of women benefit. Neoadjuvant chemotherapy prior to radiotherapy could jeopardise survival and should be avoided unless perhaps a 'quick', dose intense regimen is used. Neoadjuvant chemotherapy before surgery may be beneficial, but the approach will remain controversial until it is tested against platinum-based chemoradiotherapy. Future studies many include combinations of other cytotoxics such as topotecan with cisplatin-based concomitant chemoradiotherapy or the addition of agents targeted against specific receptors such as EGFR.

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Section: Discussionmentioning

confidence: 99%

Concomitant and Neoadjuvant Chemotherapy for Cervical Cancer

Tierney¹,

Vale²,

Symonds³

2008

Clinical Oncology

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“…3,4 Since the publication of the initial studies examining cisplatin in the treatment of cervical cancer, a number of effective single-agent and combination drug regimens have been identified that exhibited improved response rates, without a significant effect on overall survival. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] The poor oncologic outcome in this patient population represents an unmet clinical need and has driven the exploration of new treatment paradigms. 3 Most recently, the results of Gynecologic Oncology Group (GOG) protocol 240 were presented and Scan the QR Code with your phone to obtain FREE ACCESS to the articles featured in the Clinical Therapeutics topical updates or text GS2C65 to 64842.…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy: An Evolving Paradigm in the Treatment of Advanced Cervical Cancer

Eskander

Tewari

2015

Clinical Therapeutics

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Purpose: In 2014, the US Food and Drug Administration approved the first targeted agent, bevacizumab, in the treatment of advanced stage, persistent, or recurrent cervical cancer. This oncologic milestone has catalyzed interest in the investigation of alternate therapies, including immunotherapy, in an effort to extend life and possibly cure patients with advanced stage disease.Methods: This review article focuses on the evolving paradigm of immunotherapy in the treatment of cervical cancer, describing the biologic basis of this treatment modality and discussing applicable Phase I to II clinical trials.Findings: To date several trials have been conducted exploring vaccine-based therapies, adoptive T-cell therapy, and immune-modulating agents in patients with cervical cancer with promising results.Implications: Immunotherapy represents a promising therapeutic paradigm in the treatment of advanced cervical cancer. Additional investigation is warranted to try and identify alternate immune targets and predictors of response, allowing for the selection of patients most likely to benefit from immune-based treatments. (Clin Ther. 2015;37:20-38) & 2015 Elsevier HS Journals, Inc. All rights reserved.

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“…The combination of these two agents was hypothesized to cause greater antitumor activity than might be expected from the additive effects of the two drugs. Clinical trials have since proven this hypothesis in patients with advanced or recurrent cervical cancer [13,14]. Although more hematologically toxic, the combination does not appear to significantly reduce patient quality of life (QOL) when compared with cisplatin alone [15].…”

Section: Introductionmentioning

confidence: 99%

“…Although more hematologically toxic, the combination does not appear to significantly reduce patient quality of life (QOL) when compared with cisplatin alone [15]. GOG Protocol 179 was the first randomized phase III trial to demonstrate a survival advantage for the combination of cisplatin and topotecan over cisplatin alone in recurrent or stage IVB cervical cancer [14]. Topotecan is also a radiosensitizing agent [16] and has been studied at various daily dosing regimens in patients with advanced cervical cancer receiving external beam RT and low-dose rate (LDR) brachytherapy [17,18].…”

Section: Introductionmentioning

confidence: 99%

A feasibility study of topotecan with standard-dose cisplatin and concurrent primary radiation therapy in locally advanced cervical cancer

Gatcliffe

Tewari

Shah

et al. 2009

Gynecologic Oncology

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Objectives. Topotecan improves response rate (RR), progression-free survival (PFS) and overall survival (OS) when added to cisplatin in treating metastatic and recurrent cervical cancer. The objective of this study was to assess the feasibility of adding weekly topotecan to cisplatin in patients with primary, locally advanced carcinoma of the cervix receiving pelvic irradiation.Methods. Patients with primary, previously untreated, histologically confirmed invasive squamous cell, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, stages IB2-IVA were treated with external beam pelvic radiotherapy (45 Gy), intracavitary low dose rate brachytherapy (40 Gy) and a parametrial boost (5.4-9 Gy) with overall treatment time not to exceed 8 weeks. Concurrent chemotherapy was IV cisplatin 40 mg/m 2 plus IV topotecan 2 mg/m 2 on days 1, 8, 15, 22, 29 and once during parametrial boost for 6 cycles. Patients were monitored with history, physical examination, tumor measurement and laboratory evaluation before entering the study, before each cycle of chemotherapy, at study termination and every three months thereafter.Results. The study met its accrual goal of 12 patients. With a median follow-up of 22 months, eleven patients completed treatment and ten are in long term follow up without evidence of recurrent disease. The 12th patient developed progressive disease during therapy. All patients completed at least 4 cycles of chemotherapy, with the majority (82%) completing 5 or more. Grade 2 or higher neutropenia delayed treatment in 54% of cycles. The median treatment delay was 1.5 cycles (range: 1 to 5 cycles). Median treatment time was 59 days (range 46 to 81 days). The complete RR was 92% (95% confidence interval, 55%-100%).Conclusions. The addition of weekly topotecan to cisplatin at this dose and schedule during pelvic irradiation for locally advanced cervical cancer appears to be feasible. Based on this primary treatment data and the activity of cisplatin-topotecan in the recurrent disease setting, phase II and III studies of this combination are warranted.

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Randomized Phase III Trial of Cisplatin With or Without Topotecan in Carcinoma of the Uterine Cervix: A Gynecologic Oncology Group Study

Abstract: This is the first randomized phase III trial to demonstrate a survival advantage for combination chemotherapy over cisplatin alone in advanced cervix cancer.

Cited by 498 publications

References 19 publications

Concomitant and Neoadjuvant Chemotherapy for Cervical Cancer

Concomitant and Neoadjuvant Chemotherapy for Cervical Cancer

Immunotherapy: An Evolving Paradigm in the Treatment of Advanced Cervical Cancer

A feasibility study of topotecan with standard-dose cisplatin and concurrent primary radiation therapy in locally advanced cervical cancer

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