Phase i dose-escalating study of biweekly fixed-dose rate gemcitabine plus pemetrexed in patients with advanced solid tumors

Yuan Yuan, Deirdre J. Cohen, Erica Love, Michelle Yaw, Benjamin Levinson, Steven J. Nicol, Howard S. Hochster

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Purpose: To determine the maximum tolerated dose (MTD) and the recommended phase II dose and to identify the dose-limiting toxicities (DLTs) of gemcitabine, administered by fixed-dose rate (FDR) infusion, combined with the antifolate agent pemetrexed in patients with advanced solid tumors. Methods: Eligible patients were entered into this open label, phase I trial. Using a 3 + 3 dose escalation design, patients received intravenous pemetrexed 300-800 mg/m2 followed by FDR gemcitabine 900-1,500 mg/m2 at 10 mg/m2/min on Day 1 every 2 weeks. All patients received folic acid and vitamin B12 supplementation. Patients continued until DLT or disease progression. Results: A total of 33 patients were treated at 7 dose levels with a total of 230 cycles (median: 4 cycles; mean: 7 cycles; range: 1-35 cycles). The MTD of the combination was pemetrexed 800 mg/m2 and gemcitabine 1,500 mg/m2 over 150 min. DLTs were febrile neutropenia and grade 3 renal failure. Of the 28 patients evaluable for response, 3 patients experienced a partial response (10.7%) and 13 patients had stable disease (46.4%); the disease control rate was 57.1%. Conclusions: The recommended phase II dose for biweekly pemetrexed with FDR gemcitabine is 800 mg/m2 and 1,200 mg/m2 × 120 min, respectively. This regimen allows good dose intensity of both drugs to be administered on a simple schedule with an excellent tolerability profile. This regimen showed moderate activity in a diverse phase I population, possibly greater than either single agent. Further assessment of the combination in a phase II setting is suggested.

Original languageEnglish (US)
Pages (from-to)371-378
Number of pages8
JournalCancer chemotherapy and pharmacology
Issue number2
StatePublished - Aug 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)


  • Advanced solid tumors
  • Dose-limiting toxicity
  • Fixed-dose rate
  • Gemcitabine
  • Maximum tolerated dose
  • Pemetrexed


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