Pemetrexed and cisplatin as first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) with asymptomatic inoperable brain metastases: a multicenter phase II trial (GFPC 07-01)

Ann Oncol. 2011 Nov;22(11):2466-2470. doi: 10.1093/annonc/mdr003. Epub 2011 Feb 14.

Abstract

Background: Brain metastases (BM) occur in up to 40% of non-small-cell lung cancer (NSCLC) patients. This trial assessed the safety and efficacy of pemetrexed-cisplatin in this population.

Patients and methods: Chemonaive NSCLC patients with BM ineligible for (radio)surgery, performance status (PS) of 0 to 2, were eligible for up to six cycles of cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) every 3 weeks. Whole -brain radiotherapy was given in case of disease progression or at chemotherapy completion. Primary end point was objective response rate (RR) on BM. Secondary end points included extracerebral and overall RR, safety profile and survival.

Results: Forty-three patients were enrolled. Initial characteristics were mean age 60.4 years; males 29; PS: 0 in 37.2%, 1 in 60.5% and 2 in 22.3% of patients; adenocarcinoma in 36 patients, large cell in 4 patients (nonsquamous, 93%) and squamous carcinoma in 3 patients. Functional classification of neurological status was stage I/II 86.0%, III 2.3% and IV 11.6%. Grade 3-4 hematological toxic effects were neutropenia, 11 patients (febrile neutropenia, 1 patient), and anemia, 6 patients. Non-hematological toxic effects were grade 2 urinary infection, one patient; grade 3 pneumonia, two patients; and grade 3 hypoacousia, one patient. Cerebral, extracerebral and overall RR by intent to treat analysis were 41.9%, 34.9% and 34.9%, respectively. Median survival time and time to progression were 7.4 and 4.0 months, respectively.

Conclusion: Pemetrexed-cisplatin is an effective and well-tolerated regimen as first-line therapy for NSCLC patients with BM who always suffer a poor prognosis.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / secondary*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / secondary*
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Disease-Free Survival
  • Female
  • Glutamates / administration & dosage
  • Glutamates / adverse effects
  • Guanine / administration & dosage
  • Guanine / adverse effects
  • Guanine / analogs & derivatives
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Pemetrexed
  • Survival Rate

Substances

  • Glutamates
  • Pemetrexed
  • Guanine
  • Cisplatin