Weekly Paclitaxel versus Three-Weekly Paclitaxel in Recurrent Platinum-Resistant Epithelial Ovarian and Peritoneal Cancers: A Phase III Study

Abstract

INTRODUCTIONTreatment of recurrent platinum-resistant ovarian and peritoneal cancers represents a therapeutic challenge. The aim of this Phase III prospective study was to compare the survival benefits, objective response rate, and toxicities among patients treated by weekly paclitaxel with those who underwent three-weekly paclitaxel in recurrent platinum-resistant ovarian and peritoneal cancers.METHODPatients with recurrent platinum-resistant ovarian and peritoneal cancer were allocated to receive either weekly paclitaxel (arm 1) at 80 m/m2 or three-weekly paclitaxel (arm 2) at 175 mg/m2.RESULTSFifty-five patients were enrolled (30 arm 1, 25 arm 2). The mean age was 56.7 years, and the median performance status was 0 (Eastern Cooperative Oncology Group [ECOG]). For arms 1 and 2, the objective response rates were 27% and 16%, the median progression-free survival were 7 and 4.5 months, and the median overall survival were 15.5 and 12.5 months, respectively. Treatments also significantly improved the quality of life. Treatment was associated with mild toxicities, and while neuropathy was slightly higher for weekly paclitaxel over three-weekly paclitaxel, hematological toxicities were significantly lower for the former than the latter.CONCLUSIONPaclitaxel rechallenge showed antitumor activity in recurrent platinum-resistant ovarian and peritoneal cancers. Weekly paclitaxel achieved better results than three-weekly paclitaxel in terms of survival benefits, quality of life, and toxicities.

Impact of veliparib, paclitaxel dosing regimen, and germline BRCA status on the primary treatment of serous ovarian cancer – an ancillary data analysis of the VELIA trial

“…Prior retrospective study of patients with BRCA mutated ovarian cancer has demonstrated that paclitaxel, as a monotherapy, produced high response rates regardless of DD or Q3W dosing; those data also suggested increased activity in platinum-sensitive disease [ 29 ]. In patients with platinum resistant disease, however, it has been shown that DD paclitaxel resulted in better survival benefit and quality of life [ 30 ]. Here, our study showed that DD paclitaxel was associated with longer median PFS versus Q3W dosing in HRP and BRCA wt subgroups, but this effect was observed to a lesser extent in patients with a deleterious BRCA m or HRD.…”

Phase 2 study evaluating intermittent and continuous linsitinib and weekly paclitaxel in patients with recurrent platinum resistant ovarian epithelial cancer

“…Weekly paclitaxel is a common standard treatment option for women with platinum-resistant/refractory ovarian cancer. The median PFS is approximately 4.0-7.0 months, demonstrating an urgent need to develop agents that can delay taxane resistance [30,31]. The addition of antiangiogenic agents, such as bevacizumab (a VEGFA antibody), pazopanib (a multi-targeted tyrosine kinase inhibitor of VEGF receptors), and trebananib (an anti-angiopoietin), to weekly paclitaxel significantly improves PFS [6,32,33].…”

Lapatinib and poziotinib overcome ABCB1-mediated paclitaxel resistance in ovarian cancer

“…Unfortunately, over 80% of patients with advanced ovarian cancer who achieve a complete response with conventional first-line chemotherapy will develop recurrent disease [ 5 ]. Despite modest response rates for all regimens (20–30%), dose-dense paclitaxel is a preferred agent in treating platinum-resistant recurrence [ 6 – 8 ]. Virtually all relapsed patients will die of disease, highlighting the pressing need for novel therapies.…”