Pemetrexed maintenance therapy in patients with malignant pleural mesothelioma

J Thorac Oncol. 2006 Jan;1(1):25-30.

Abstract

Purpose: To investigate the toxicity and effectiveness of pemetrexed maintenance therapy (PMT) in patients with malignant pleural mesothelioma (MPM).

Patients and methods: Eligible were patients with histologically proven advanced MPM, WHO PS 0-2 and adequate hematological, renal and hepatic function in whom during 6 courses of pemetrexed containing induction therapy no disease progression was observed. PMT, 500 mg/m intravenously on day 1 every 3 weeks, was continued until disease progression, unacceptable toxicity, or if continuation was considered to be not in the patient's best interest. Written informed consent was obtained from all patients.

Results: Of the 27 patients who received induction therapy, 13 were treated with PMT. The median number of PMT courses was 4 (range = 2 to 14). No grade 4 toxicity was observed. Grade 3 neutropenia, leucopenia and anemia occurred 15%, 8% and 8%, respectively. The only non-hematological grade 3 toxicity during PMT was fatigue (15%). During PMT creatinine clearance decreased from 88 (+/-21) ml/min to 77 (+/-26) ml/min (p < 0.05). The reason to stop PMT was disease progression (69%), toxicity (23%) and in patient's best interest (8%). During PMT 23% of the patients with stable disease after induction therapy achieved a partial response. Time to progression and overall survival were 3.4 and 6.0 months versus 8.5 and 17.9 months, respectively (p < 0.0001).

Conclusions: PMT in MPM patients is non-toxic, well tolerated and although promising effects on TTP and OS are demonstrated, the effectiveness of PMT should be further explored in a prospective randomized clinical trial.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Glutamates / administration & dosage
  • Glutamates / therapeutic use*
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Humans
  • Injections, Intravenous
  • Male
  • Mesothelioma / drug therapy*
  • Mesothelioma / mortality
  • Mesothelioma / pathology
  • Middle Aged
  • Neoplasm Staging
  • Netherlands / epidemiology
  • Pemetrexed
  • Pleural Neoplasms / drug therapy*
  • Pleural Neoplasms / mortality
  • Pleural Neoplasms / pathology
  • Retrospective Studies
  • Survival Rate / trends
  • Thymidylate Synthase / antagonists & inhibitors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Glutamates
  • Pemetrexed
  • Guanine
  • Thymidylate Synthase