A phase II, pharmacokinetic (PK), and pharmacodynamic (PD) study of weekly docetaxel (DOC) in patients with platinum-resistant ovarian cancer

Abstract

e16531 Background: DOC at 30 mg/m2 q wk for 3 wks q 4 wks was modestly active and minimized toxicity in patients (pts) with platinum resistant epithelial ovarian cancer compared to historical data of DOC at 75 to100 mg/m2 q 21 days (Berkenblit, Gynecologic Oncology 2004). However, the optimal schedule of weekly DOC in pts with ovarian cancer has not been determined. Our study assessed the activity and safety of weekly DOC at 36 mg/m2 q wk for 6 wks q 8 wks in platinum and paclitaxel resistant ovarian cancer. PK and PD studies of DOC were performed on wks 1 and 6. Methods: Pts (n = 25) with platinum and paclitaxel resistant ovarian cancer with up to 3 previous treatments were eligible. DOC was administered at 36 mg/m2 IV over 30 min q wk for 6 wks repeated q 8 wks until complete response or disease progression. Plasma samples were obtained from 0 to 24 h after administration of DOC on wks 1 and 6 of cycle 1. DOC plasma conc were determined by liquid chromatography mass spectrometry (LC-MS). Non-compartmental analysis of area under the plasma conc versus time curves (AUC) was calculated by WonNonLin. Results: Of the 25 pts, 6 pts (24%) had a partial response (PR) and 4 pts (16%) had stable disease using GCIG criteria or NCI RECIST criteria. Median duration of response in these 10 pts (40%) was 16.5 wks. Median survival was 32.5 wks with 4 out of 10 pts alive with disease. Hematological toxicity was mild with 20% grade 3 anemia and 20% grade 3/4 neutropenia. Mean ± SD DOC AUC on wks 1 and 6 were 2,520 ± 1,017 and 2,808 ± 1,247 ng/mL·h, respectively. Mean ± SD ratio of DOC AUC on wk 6 to wk 1 for each pt was 1.11 ± 1.23. Conclusions: DOC at 36 mg/m2 q wk for 6 wks q 8 wks was active and well tolerated, and offered meaningful palliation in pts with platinum and paclitaxel ovarian cancer. Significant reduction in hematological toxicity over standard DOC schedule was observed. There is high inter-patient and low intra-patient variability in the PK of DOC from wk 1 to wk 6. No significant financial relationships to disclose.