Phase I/II trial of pemetrexed plus nab-paclitaxel in advanced solid tumor patients with emphasis on non-small cell lung cancer
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Background Despite advances in targeted therapies, there is an ongoing need to develop new and effective cytotoxic drug combinations in non-small cell lung cancer (NSCLC). Based on preclinical demonstration of additive cytotoxicity, we evaluated the safety and efficacy of combining pemetrexed and nanoparticle albumin bound (nab) paclitaxel with a focus on NSCLC for phase II expansion. Methods A 3 + 3 dose-escalation design was used to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D). Three dose levels were tested: pemetrexed 500 mg/m2 day 1 and nab-paclitaxel day 1 at 180, 220, & 260 mg/m2 every 21 days. Phase II eligibility included advanced NSCLC, ≤2 line prior therapy, PS 0–1, adequate organ function. Primary endpoint for further study was response rate (RR) ≥ 25 %. Results Planned dose escalation was completed without reaching the MTD. The RP2D was pemetrexed 500 mg/m2 and nab-paclitaxel 260 mg/m2. The phase II portion accrued 37 pts before early closure due to increasing first-line pemetrexed/platinum doublet use in non-squamous NSCLC. In 31 assessable phase II patients there were 5 partial responses, 12 stable disease, 14 progressive disease. The median overall survival was 8.8 months; progressive disease 4.4 months and disease control 15.6 months. Conclusions Pemetrexed 500 mg/m2 day 1 with nab-paclitaxel 260 mg/m2 was feasible and well tolerated. The phase II component demonstrated activity in second/third-line therapy of advanced NSCLC; response rate 14 % and disease control rate 46 %. Treatment practice patterns of advanced NSCLC have evolved; further trials of this regimen are not planned.
KeywordsPhase II Pemetrexed Nab-paclitaxel Nanoparticle albumin bound paclitaxel Non small cell lung cancer
The authors are thankful for the expert administrative support of Grace Loredo in conducting this study.
Support for this trial was provided by the UC Davis Cancer Center, Eli Lilly and Company and Abraxis BioScience (a wholly-owned subsidiary of Celgene Corporation).
Conflict of interest
The authors declare that they have no conflict of interest.
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