Phase II trial of paclitaxel polyglumex (PPX) with capecitabine (C) for metastatic breast cancer (MBC)

Abstract

1063 Background: C is an established effective treatment, alone and combined with paclitaxel (P), for MBC. P causes alopecia, infusion reactions, requires corticosteroid premedication and lengthy infusion time which make therapy problematic. PPX (macromolecular conjugate of P bound to poly-L-glutamic acid) has potential advantages over P including little alopecia, short infusion time with no premedication, enhanced tumor permeability/retention effect, and estrogen-influenced metabolism which may improve tolerability and efficacy. We therefore examined tolerability and efficacy of PPX + C in patients with MBC. Methods: Single stage phase II study, interim analysis conducted with endpoints of tumor response, adverse events (AE), time to progression and overall survival. Main eligibility: age >18, no prior MBC chemotherapy, ECOG PS<2, RECIST-measurable disease, HER2-neg, no brain mets or neuropathy. Treatment: PPX 135 mg/m2 day 1 + C 825 mg/m2 BID days 1–14, 3-week cycle. 41 evaluable patients required to test null hypothesis that complete and partial tumor response rate (CR + PR) was at most 40% against the alternative of at least 60%. PPX + C would be considered promising in this population if ≥21 responses observed among first 41 evaluable patients. Results: 48 patients enrolled April 2006- April 2007; all patients evaluable. Median cycles administered = 6. 20 patients (42%; 95% CI: 28–57%) had tumor response (2 CR, 18 PR) by RECIST criteria. All 20 (49%, 95% CI: 33%-65%) responses occurred in first 41 patients, falling short of trial goal of 21. Median duration of tumor response = 11.9 months. Median follow-up = 7.6 months. Median progression-free survival = 5.7 months (95% CI: 4.2–10.0 months). 6-month overall survival = 86% (95% CI: 76–97%); progression free survival = 45% (95% CI: 32–62%). Median dose level administered = 135 mg/m2 PPX, 825 mg/m2 C for cycles 1–7. Most common severe (grade 3/4) AE: leukopenia 9 (18%), neutropenia 8 (20%), neuro-sensory 4 (9%), skin reaction-hand/foot 4 (9%), dyspnea 3 (6%). 53% (25/47) of patients experienced a grade ≥3 AE and 13% experienced a grade ≥4 AE. No alopecia was reported. Conclusions: Although the trial failed to reach goal of 21 confirmed tumor responses in the first 41 evaluable patients, PPX + C is well tolerated and active in MBC. No significant financial relationships to disclose.