Timing and duration of bevacizumab treatment and survival in patients with recurrent ovarian, fallopian tube, and peritoneal cancer: a multi-institution study

Abstract

Bevacizumab has demonstrated significant benefit in recurrent ovarian, fallopian tube and peritoneal cancer (OC), but its optimal position within the sequence of systemic therapies remains controversial. Since rebound progression after bevacizumab has been observed in other cancers, and because bevacizumab is incorporated in several regimens used in the recurrent setting, the duration of treatment may impact survival. We sought to identify whether earlier bevacizumab exposure is associated with prolonged bevacizumab therapy and survival by conducting a multi-institution retrospective study of recurrent OC patients treated with bevacizumab from 2004–2014. Multivariate logistic regression identified factors associated with receiving more than six bevacizumab cycles. Overall survival by duration and ordinal sequence of bevacizumab therapy were evaluated using logrank testing and Cox regression. In total, 318 patients were identified. 89.1% had stage III or IV disease; 36% had primary platinum resistance; 40.5% received two or fewer prior chemotherapy regimens. Multivariate logistic regression demonstrated that primary platinum sensitivity (Odds Ratio (OR) 2.34, p = 0.001) or initiating bevacizumab at the first or second recurrence (OR 2.73, p < 0.001) were independently associated with receiving more than six cycles of bevacizumab. Receiving more cycles of bevacizumab was associated with improved overall survival whether measured from time of diagnosis (logrank p < 0.001), bevacizumab initiation (logrank p < 0.001), or bevacizumab discontinuation (logrank p = 0.017). Waiting one additional recurrence to initiate bevacizumab resulted in a 27% increased hazard of death (Hazard Ratio (HR) 1.27, p < 0.001) by multivariate analysis. In conclusion, patients with primary platinum sensitive disease who received fewer prior lines of chemotherapy were able to receive more cycles of bevacizumab, which was associated with improved overall survival. Survival worsened when bevacizumab was initiated later in the ordinal sequence of therapies.

Alisma orientale extract inhibits cell proliferation by promoting oxidative stress and apoptosis in prostate cancer cells

“…Notably, AOE can hinder cell growth by inducing oxidative stress and apoptosis in these cells, highlighting its potential as a promising candidate for prostate cancer therapy. AOE, isolated from rhizoma alismatis, possesses a range of beneficial effects, such as reducing blood lipids, blood pressure and blood sugar, and also has preventive properties against atherosclerosis and fatty liver [13,16]. Alisma contains triterpenoids, which can significantly lower cholesterol and triglyceride levels in the blood and aid in averting atherosclerosis and reducing the risk of cardiovascular and cerebrovascular diseases [8,9].…”

Magnoflorine inhibits cisplatin-induced protective autophagy by down-regulating HMGB1 and increases drug sensitivity in drug-resistant ovarian cancer cells

“…Autophagy represents the primary pathway responsible for the degradation of non-functional proteins and organelles [4,5]. Numerous studies have highlighted the close association between autophagy and cancer, with its impact on the sensitivity of tumor cells to chemotherapy drugs is well-documented [6][7][8]. Thus, inhibiting cisplatin-induced protective autophagy in OC presents a potentially promising strategy against drug resistance [9].…”

Inhibition of MARK2 inhibits ovarian cancer cell proliferation by regulating PI3K/AKT/p53 axis

“…OC remains one of the most challenging types of malignancies [2]. At present, the clinical treatment of OC is mainly surgery as well as chemotherapy, but targeted therapy is also can be selected [1,4]. Targeted therapy generally includes two types, poly-ADP-ribose polymerase (PARP) inhibitors and anti-angiogenesis drugs, which can be applied to the first-line maintenance therapy for advanced ovarian cancer with limited efficacy [5].…”