Cetuximab, topotecan and cisplatin for the treatment of advanced cervical cancer: A phase II GINECO trial

Kurtz, Jean Emmanuel; Hardy‐Bessard, Anne‐Claire; Deslandres, Marion; Lavau‐Denès, Sandrine; Largillier, R.; Roemer-Bécuwe, C.; Weber, B.; Guillemet, Cécile; Paraïso, D.; Pujade-Lauraine, Éric

doi:10.1016/j.ygyno.2008.12.040

Cited by 82 publications

(41 citation statements)

References 13 publications

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Section: Cetuximab and Cervical Cancermentioning

confidence: 95%

“…The severe hematological toxicities notwithstanding, an overall response rate of 32% was demonstrated despite the abbreviated study interval, indicating significant activity of the cetuximab-containing regimen. 7 The median progression-free and overall survival observed were 5.7 and 7.3 months, respectively.Several GOG studies regarding the use of cetuximab for the treatment of cervical cancers are ongoing, including a study of the efficacy of single-agent cetuximab in recurrent cervical cancer, a phase I trial of tailored radiation therapy with concomitant cetuximab and cisplatin as radiosensitizers in primary cervical cancer, and a phase II trial comparing cetuximab combined with cisplatin for recurrent or persistent cervical cancers. …”

mentioning

confidence: 95%

“…21 Thus, the goal for these patients is palliation of symptoms while preserving quality of life, and systemic chemotherapy remains the mainstay of therapy. 7,16,17,19,21,24 In the early 1980s, cisplatin was first …”

mentioning

confidence: 99%

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Cisplatin plus Cetuximab in the Treatment of Recurrent and Persistent Cancers of the Cervix

Oliver¹,

Farley²

2010

Oncology &Amp; Hematology Review (US)

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Targeted molecular therapies comprise the newest frontier of oncology research. [1][2][3] Recent investigations have concentrated on the development of novel treatments designed to interrupt cellular pathways crucial to oncogenesis and, in fact, these medications represent a large proportion of drugs undergoing evaluation in current and new clinical trials.2 Identification of the intracellular signals responsible for conferring malignant potential on tumor cells enables therapeutic discrimination between malignant and healthy cells. 1,2 The expectation is that targeted therapies, in contrast to traditional chemotherapeutic agents, will provide enhanced patient outcomes and improved efficacy in the setting of superior, or at least complementary, toxicity profiles. 3 Furthermore, targeted drugs provide alternative approaches to disruption of carcinogenesis, which may prove to be synergistic with conventional cancer therapies. While the advent of innovative treatment modalities for cancers has improved the landscape for affected patients, the overall response to therapy thus far has been modest. Epidermal Growth Factor ReceptorNon-malignant cells develop in a regulated fashion using a series of This response compared favorably with the data for the single-agent Gynecologic Cancer be treated successfully and with equal efficacy using either radical surgery or radiation. 20 However, approximately 25% of women have advanced disease at diagnosis, and the overall survival for these patients is low, even with multimodality therapies. 9 Furthermore, despite improvements in treatment, up to 35% of women will eventually develop persistent, recurrent, or metastatic cervical cancers, which will respond only briefly to platinum-based chemotherapy. 8,17Historically, radiation was the mainstay of treatment for locally advanced cervical cancer. 21 In 1999, five large clinical trials from the Gynecologic Oncology Group (GOG), Southwest Oncology Group (SOG), and Radiation Therapy Oncology Group (RTOG), encompassing more than 1,800 patients, published remarkably consistent data that changed the landscape of treatment of cervical cancer. 11,16,22,23 These trials each demonstrated a reduction in relative risk of death of 30-50% with the addition of concurrent cisplatin chemotherapy as a radiosensitizer. 11,16These data led the NCI to endorse platinum-based chemotherapy for the treatment of locally advanced cervical cancer. Since then, single-agent cisplatin with radiation has been the mainstay of treatment, and it continues to be the most active chemotherapeutic agent in cervical cancer. 17,21,23 More recently, the GOG has conducted several trials aimed at the identification of other single or multi-agent radiosensitizer regimens that demonstrate improved response and overall survival rates while maintaining satisfactory quality of life. 11,16,22 Recurrent cervical cancer usually cannot be cured, particularly when surgical resection is not feasible and radiation salvage is not possible secondary to previous treatment, or when patie...

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Section: Cetuximab and Cervical Cancermentioning

confidence: 95%

mentioning

confidence: 95%

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Cisplatin plus Cetuximab in the Treatment of Recurrent and Persistent Cancers of the Cervix

Oliver¹,

Farley²

2010

Oncology &Amp; Hematology Review (US)

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“…Based on these results, cetuximab did not provide a survival advantage over cisplatin. The French trial of cetuximab (initial dose of 400 mg/m 2 followed by subsequent weekly dose of 250 mg/m 2 ) with cisplatin (50 mg/m 2 ) plus topotecan (0.75 mg/m 2 on days 1-3 every 3 weeks) in advanced cervical cancer was prematurely terminated due to serious toxicities and high mortality (28%) (Kurtz et al 2009). …”

Section: Phase II Trialsmentioning

confidence: 99%

Cytotoxic and Targeted Systemic Therapy in Advanced and Recurrent Cervical Cancer: Experience from Clinical Trials

Seol

Ulak

et al. 2014

Tohoku J. Exp. Med.

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Cervical cancer is the third most common malignant disease of women worldwide. Despite advances in screening and treatment strategies, a significant number of patients have advanced and recurrent disease. These patients are not amenable to curative treatments, such as surgery and radiation, and have poor prognosis. Therefore, palliative treatment remains the standard of care for these patients. Several phase II/III trials have demonstrated that cisplatin is the most active single agent, and the combination of cisplatin and paclitaxel is considered a standard regimen for clinical practice and trials in these patients with improved response rates and progression-free intervals. Although other cisplatin doublet chemotherapy regimens were not superior to cisplatin plus paclitaxel, substituting topotecan or gemcitabine for paclitaxel might be helpful for some patients considering different toxicity profiles. Because the response to palliative chemotherapy is poor, several targeted agents including bevacizumab, erlotinib, pazopanib, lapatinib, sunitinib and cetuximab, each of which inhibits cell proliferation and angiogenesis, were evaluated in these patients. Of them, bevacizumab, targeting vascular endothelial growth factor, showed favorable results. Recent phase III trial showed that bevacizumab combined with chemotherapy was shown to significantly improve the response rate, progression-free interval, and overall survival compared to chemotherapy alone. These results suggest that targeted agents could significantly improve survival and affect practice guidelines in these patients showing poor prognosis. Thus, future trials using newly developed targeted agents are warranted to improve treatment strategies in these patients.

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“…In the study by Kurtz et al (27), 44 patients with advanced cervical carcinoma were treated with cetuximab, a chimeric anti-EGFR monoclonal antibody, in combination with cisplatin and topotecan. Unfortunately, this study was stopped early due to severe bone marrow toxicity and life-threading infections.…”

Section: Receptor Kinasesmentioning

confidence: 99%

Molecular targets for therapeutic interventions in human papillomavirus-related cancers (Review)

Ramalho

Lopes²,

Talans³

et al. 2010

Oncol Rep

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Abstract. The infection by the human papillomavirus (HPV)is the origin of several cancers around the world. In some areas of Brazil, cervical carcinoma is still the cancer with the highest incidence among women. After epithelial cell transformation by HPV, several molecular events are observed, resulting in the malignant phenotype. In this review we discuss potential molecular targets for therapeutic interventions in human HPV-related carcinomas, with emphasis on cervical cancer, based on the alterations observed in the signaling transduction pathways caused by HPV infection. With a special attention to tyrosine kinase receptors, and other kinases involved in signal transduction and angiogenesis, these pathological alterations are evaluated as novel targets for anticancer therapies in HPV-related carcinomas.

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Cetuximab, topotecan and cisplatin for the treatment of advanced cervical cancer: A phase II GINECO trial

Cited by 82 publications

References 13 publications

Cisplatin plus Cetuximab in the Treatment of Recurrent and Persistent Cancers of the Cervix

Cisplatin plus Cetuximab in the Treatment of Recurrent and Persistent Cancers of the Cervix

Cytotoxic and Targeted Systemic Therapy in Advanced and Recurrent Cervical Cancer: Experience from Clinical Trials

Molecular targets for therapeutic interventions in human papillomavirus-related cancers (Review)

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