Improved Survival with Bevacizumab in Advanced Cervical Cancer

Abstract

Background-Vascular endothelial growth factor (VEGF) promotes angiogenesis, a mediator of disease progression in cervical cancer. Bevacizumab, a humanized anti-VEGF monoclonal antibody, has single-agent activity in previously treated, recurrent disease. Most patients in whom recurrent cervical cancer develops have previously received cisplatin with radiation therapy, which reduces the effectiveness of cisplatin at the time of recurrence. We evaluated the effectiveness of bevacizumab and nonplatinum combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer.

A pilot study of nimotuzumab plus single agent chemotherapy as second- or third-line treatment or more in patients with recurrent, persistent or metastatic cervical cancer

“…At a median follow-up time of 20.8 months, there was a statistically significant difference in favor of the bevacizumab containing arm with a median OS of 13. 10 Nevertheless, these results were not reproduced in a phase II study in which bevacizumab was added to the cisplatin-topotecan doublet. 11 Treatment resulted in excessive toxicity and median survival of 13.4 months, which was similar to the control arm in the GOG-240 study.…”

Trial watch: Tumor-targeting monoclonal antibodies for oncological indications

“…Moreover, the combinatorial administration of bevacizumab plus paclitaxel increased the incidence of moderate to severe hypertension, as well as that of severe thromboembolic events and gastrointestinal fistulas. 59 Based on these findings, the US FDA extended the approval of bevacizumab (in combination with paclitaxel plus cisplatin of paclitaxel plus topotecan) to the treatment of persistent, recurrent or metastatic cervical cancer.…”

“…Bevacizumab (Avastin Ò , Genentech, Inc.), a humanized vascular endothelial growth factor A (VEGFA)-targeting IgG1 that was previously approved for the treatment of some forms of glioblastoma, colorectal carcinoma (CRC), renal cell carcinoma (RCC) and non-small cell lung carcinoma (NSCLC), 23,[53][54][55] is now indicated for the therapy of persistent, recurrent or metastatic cervical cancer, in combination with paclitaxel (a microtubular poison of the taxane family), [56][57][58] and cisplatin (a DNAdamaging agent) or paclitaxel and topotecan (a topoisomerase inhibitor). 59 Moreover, ofatumumab (Arzerra Ò , GlaxoSmithKline), a CD20-specific human IgG1 licensed in 2009 for the treatment of previously treated CLL patients, [60][61][62][63] can now be used also in treatment-na€ ıve CLL patients for whom fludarabinebased therapy is considered inappropriate. 64,65 Overall, this raises the number of tumor-targeting mAbs currently approved for oncological indications to 17 ( Table 1).…”

Remodeling of angiogenesis and lymphangiogenesis in cervical cancer development

“…В 2014 году Tewari и соавт. опубликованы результаты III фазы клинических испытаний бевацизумаба в комплексе со стандартной химиотерапией при лечении метастатического и рецидивирующего РШМ ("GOG 240, Gynecologic Oncology Group"), в рамках которого показано достоверное увеличение периода ремиссии и продолжительности жизни больных [42,43]. В клиническом испытании "Radiation Therapy Oncology Group clinical trial 0417" также продемонстрировано увеличение показателей эффективности лечения при сочетании химиорадиотерапии с бевацизумабом при лечении женщин с IB-IIIB стадией РШМ [44].…”

“…Эта гибкость регуляторных механизмов, избыточность и лёгкая взаимозаменяемость отдельных их компонентов является существенным обстоятельством, осложняющим использование антиангиогенной терапии. Селективное подавление какого-либо из сигнальных путей ангиогенеза вызывает компенсаторную активацию альтернативных механизмов [42]. Исследования так называемых "не-VEGF-зависимых" путей ангиогенеза при прогрессии ЦИН/РШМ только начинают развиваться.…”