Published in:
01-08-2011 | Original Article
Phase I dose-escalating study of biweekly fixed-dose rate gemcitabine plus pemetrexed in patients with advanced solid tumors
Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2011
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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.