A phase II study of the combination chemotherapy of bevacizumab and gemcitabine in women with platinum-resistant recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer

Abstract

Introduction: Bevacizumab and gemcitabine are key drugs for treating recurrent epithelial ovarian cancer. However, information about the combination of bevacizumab and gemcitabine is insufficient. We conducted a phase II study to assess the feasibility, clinical activity, and toxicity of this combination chemotherapy. Methods: This study included women with platinum-resistant recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer who received one to three regimens of platinum-based chemotherapy between April 1, 2015 and December 31, 2018. The patients received bevacizumab 15 mg/kg intravenously on day 1 and gemcitabine 1000 mg/m 2 intravenously on days 1 and 8 every 21 days until disease progression or unacceptable toxicity. The primary endpoint was the completion rate of three cycles of chemotherapy. This study was registered in the University Medical Information Network (UMIN) Clinical Trials Registry (UMIN000016619). Results: Among the 19 patients, 18 (95%) received ≥3 and 9 (47%) received ≥6 cycles of the study therapy. The objective response rate was 42% (complete response of 16% and partial response of 26%), and the clinical control rate was 84%. Hematological toxicity included neutropenia grade 3/4 in 9 patients (47%), anemia grade 3/4 in 2 (11%), and thrombocytopenia grade 3/4 in 1 (5%). One patient (5%) had grade 3 hypertension, and 1 (5%) had grade 3 protein urea. Possibly related grade 3 pulmonary toxicity was observed in 1 patient. Three patients needed dose reduction of gemcitabine to 800 mg/m 2 due to treatment delay by 15 to 21 days on day1. There was no treatment delay more than 14 days on day 8. The median progression-free survival duration was 5.1 months and median overall survival duration was 21.3 months. Conclusion: The combination chemotherapy with gemcitabine and bevacizumab was feasible, effective and safe. This combination chemotherapy may be explored in a further randomized trial.

A Retrospective Observational Study of Anlotinib in Patients with Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer

“…Non-platinum-based agents or regimens are preferred (ie, docetaxel, oral etoposide, gemcitabine, weekly paclitaxel with or without pazopanib, liposomal doxorubicin with or without bevacizumab, weekly paclitaxel/bevacizumab) sequential therapy is usually performed with a single agent. 6,11,[19][20][21][22] Although notable progress has been made in the treatment of ovarian cancer, the prognosis of patients with the resistant or refractory disease remains poor. 4,23 Beyond chemotherapy, molecular targeted therapy plays an important role in the treatment of platinumresistant or platinum-refractory ovarian cancer.…”

“…28 Bevacizumab combined with chemotherapy shown improved activity in platinum-resistant ovarian cancer. 6,11,12,[29][30][31][32] In AURELIA, the PFS of chemotherapy plus bevacizumab in patients with platinum-resistant disease is 6.7 months. However, the prolongation of OS in the bevacizumab group did not reach a significant level.…”

“…[7][8][9][10] Some studies have shown that the combination of chemotherapy and the angiogenesis inhibitor was effective for platinum-resistant or platinumrefractory ovarian cancer. 11,12 Some researchers have explored the combination of anti-angiogenic therapy and immunotherapy in ovarian cancer. 13 Anlotinib is an oral small-molecular TKI with the suppression of tumor growth and angiogenesis.…”

Efficacy of Gemcitabine and Bevacizumab Combination Chemotherapy for Platinum-Resistant Recurrent Ovarian Cancer: A Retrospective Analysis

“…However, the results of subanalyses suggested that only multidrug therapy with bevacizumab and paclitaxel improved both PFS and OS 13) . Nagao et al reported that when Ben-Gem therapy was administered to PSR patients, the median PFS and OS were 5.1 months and 21.3 months, respectively, and that Ben-Gem therapy was effective and safe 12) .…”

“…It has been reported that monotherapy with gemcitabine is effective for PRR disease 9,10) . However, there are only a limited number of reports on multidrug therapy with gemcitabine and bevacizumab (Bev-Gem therapy) 11,12) . Thus, we performed a retrospective study to evaluate the efficacy and safety of Bev-Gem therapy in PROC patients.…”