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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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1587-1591
Number of pages5
JournalInvestigational New Drugs
Volume31
Issue number6
DOIs
StatePublished - Dec 2013

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Keywords

  • Nab-paclitaxel
  • Nanoparticle albumin bound paclitaxel
  • Non small cell lung cancer
  • Pemetrexed
  • Phase II

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

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