Phase I trial of pemetrexed plus oxaliplatin administered every other week in patients with metastatic cancer

Invest New Drugs. 2008 Aug;26(4):339-45. doi: 10.1007/s10637-008-9133-4. Epub 2008 May 8.


Purpose: To identify the maximum tolerated dose (MTD) and describe dose-limiting toxicities (DLT) of pemetrexed and oxaliplatin given on a once-every-2-week schedule in patients with metastatic cancer.

Patients and methods: Twenty-five patients were enrolled. Due to toxicities observed at the first dose level in unselected patients, a second MTD was determined in patients who had received zero to two prior chemotherapy regimens.

Results: DLT was observed at dose level 1-pemetrexed 400 mg/m(2) and oxaliplatin 85 mg/m(2)-in the form of grade 3 fatigue in two of six patients. Enrollment was then limited to lightly pretreated patients and DLT was observed at dose level 2-pemetrexed 500 mg/m(2) and oxaliplatin 85 mg/m(2)-in the form of neutropenic fever in one of five patients. Complete response was confirmed in one patient (squamous cell carcinoma of the head and neck) and partial response was confirmed in three patients.

Conclusions: The combination of pemetrexed and oxaliplatin can be safely administered at doses of 400 to 500 mg/m(2) of pemetrexed and 85 mg/m(2) in patients without extensive prior therapy and 300 and 85 mg/m(2), respectively, every 2 weeks in patients with more extensive prior therapy. Based on promising results observed in this study, a phase II trial in patients with recurrent head and neck cancer has been initiated.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / pathology
  • Dose-Response Relationship, Drug
  • Fatigue / chemically induced
  • Female
  • Glutamates / administration & dosage
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Metastasis / drug therapy*
  • Neutropenia / chemically induced
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Pemetrexed


  • Glutamates
  • Organoplatinum Compounds
  • Pemetrexed
  • Oxaliplatin
  • Guanine