Dose-escalation study of thoracic radiotherapy in combination with pemetrexed plus Cisplatin followed by pemetrexed consolidation therapy in Japanese patients with locally advanced nonsquamous non-small-cell lung cancer

Clin Lung Cancer. 2013 Jan;14(1):62-9. doi: 10.1016/j.cllc.2012.03.007. Epub 2012 May 24.

Abstract

Background: Pemetrexed has radiosensitizing potential when evaluated in vitro in combination with platinum-containing compounds and radiation. We determined the recommended dose (RD) of thoracic radiotherapy (TRT) with a concurrent chemotherapy combination of pemetrexed and cisplatin in Japanese patients with nonsquamous non-small-cell lung cancer (NSCLC).

Patients and methods: Eligible patients were histologically confirmed as having locally advanced nonsquamous NSCLC. Study treatment consisted of 2 phases: concurrent chemoradiation and consolidation. In the concurrent chemoradiation phase, all patients received pemetrexed 500 mg/m(2) plus cisplatin 75 mg/m(2) on day 1 of a 21-day interval for 3 cycles. The first 6 patients were given 60 Gy concurrently at level 1 dose (L1D). If dose-limiting toxicity (DLT) occurred in < 2 patients at L1D, radiation was escalated to 66 Gy (level 2 dose [L2D]).

Results: Eighteen patients were treated and completed chemoradiotherapy; 12 completed the consolidation phase. In the concurrent chemoradiation phase, 1 patient experienced 2 DLTs [grade 3 anorexia and diarrhea] at L1D. Because no DLT was observed at L2D, it was determined to be the RD. Common toxicities ≥grade 3 were neutropenia and leukopenia. At L1D, 1 patient each experienced grade 2 and grade 3 pneumonitis, and 2 patients experienced grade 2 esophagitis. Six patients experienced grade 2 pneumonitis and 3 patients experienced grade 2 esophagitis at L2D. Fifteen patients achieved partial response (PR), 2 had stable disease (SD), and 1 had progressive disease (PD).

Conclusion: Expected toxicities from concurrent chemoradiation were not worsened with concurrent TRT at a total dose of 66 Gy combined with pemetrexed in Japanese patients with locally advanced (LA) nonsquamous NSCLC.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Anorexia / etiology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Chemoradiotherapy / adverse effects*
  • Cisplatin / administration & dosage
  • Consolidation Chemotherapy
  • Diarrhea / etiology
  • Esophagitis / etiology
  • Female
  • Glutamates / administration & dosage
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives
  • Humans
  • Japan
  • Leukopenia / etiology
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Neutropenia / etiology
  • Pemetrexed
  • Pneumonia / etiology
  • Radiotherapy Dosage
  • Treatment Outcome

Substances

  • Glutamates
  • Pemetrexed
  • Guanine
  • Cisplatin