Cyclophosphamide-Bevacizumab as Second-Line Chemo in Advanced Recurrent Cervical Cancer

Platinum-based chemotherapy is considered the standard treatment for advanced or recurrent cervical cancer, and a combination regimen of paclitaxel, platinum, and bevacizumab (Avastin and its FDA-approved biosimilar Mvasi, is widely recognized as the standard treatment. But some cervical cancer patients with advanced or recurrent disease suffer from anaphylaxis after taxane- or platinum-based therapy, and there is no standard treatment for progressive disease that develops during or shortly after platinum-based chemotherapy. Doctors and patients have therefore sought the development of a non-taxane, non-platinum regimen for recurrent cervical cancer.

A recent Japanese case report of 4 women with recurrent cervical cancer, published in Gynecologic Oncology Reports, suggests that bevacizumab with metronomic chemotherapy (treatment in which low doses of anticancer drugs are given on a continuous or frequent, regular schedule such as daily or weekly, usually over a long period of time) of low-dose oral cyclophosphamide (CFA) should be considered for second-line chemotherapy.

The study, by Rose Isono-Nakata, MD, and colleagues, treated 4 patients with recurrent cervical cancer using a regimen of 50 mg of oral CFA daily and 15 mg/kg of bevacizumab (BEV) repeated every 3 weeks (CFA-BEV). The 4 patients followed in the report had no cancer-associated symptoms prior to the initiation of CFA-BEV therapy. The researchers therefore considered metronomic chemotherapy with bevacizumab because it could potentially prolong tumor stabilization with mild toxicity rather than the rapid and short-term regression responses caused by standard MTD therapy.

The researchers report that 1 patient had disease progression after 4 months, but the other 3 continued the regimen until their last follow-up at 13, 14, and 15 months, respectively. One patient suffered from grade 3 neutropenia; however, no grade 2 or higher non-hematological toxicities were observed.

Among the 3 patients who received salvage chemotherapy, 1 had a progression-free survival (PFS) of 4.2 months and the other 2 continued treatment for more than 13 months without disease progression. One patient continued the regimen as maintenance chemotherapy for more than 13 months after radiotherapy for metastases in the pubic region and surrounding soft tissues.

The researchers conclude that CFA-BEV could be a promising potential treatment for patients who experience recurrent disease shortly after platinum treatment, anaphylaxis in response to paclitaxel or platinum, or peripheral neuropathy.

“These cases demonstrate the use of CFA-BEV with minimal toxicity and expected anti-cancer activity and indicate that this regimen should be considered for second-line chemotherapy in advanced recurrent cervical cancer,” they noted. “In addition, the application of this therapy regimen to asymptomatic patients with minor or dormant recurrent disease should be further investigated.”

Reference

Isono-Nakata R, Tsubamoto H, Ueda T, Inoue K, Shibahara H. Bevacizumab with metronomic chemotherapy of low-dose oral cyclophosphamide in recurrent cervical cancer: four cases. Gynecol Oncol Rep. 2018 April 6;24:57-60. doi: 10.1016/j.gore.2018.04.001.