Phase I study of concurrent chemoradiation with pemetrexed and cisplatin followed by consolidation pemetrexed for patients with unresectable stage III non-small cell lung cancer

Lung Cancer. 2011 Oct;74(1):69-74. doi: 10.1016/j.lungcan.2011.01.021. Epub 2011 Feb 24.

Abstract

Purpose: Although concurrent chemotherapy and radiation is the standard approach for good risk unresectable stage III non-small cell lung cancer (NSCLC) patients, there is no optimal concurrent chemotherapy regimen. Administration of chemotherapy at full dose with maximal activity against local and micrometastatic disease is highly desirable. This study tested the feasibility of 3 cycles of full dose cisplatin and pemetrexed concurrent with definitive thoracic radiotherapy followed by consolidation pemetrexed, without the dose-limiting toxicity (DLT) exceeding 33% of the patients.

Methods: Patients with unresectable stage III NSCLC, good performance status and no serious comorbidity were eligible. Patients received thoracic radiation to a dose of 66 Gy concurrently with three 21-day cycles of pemetrexed 500 mg/m(2), and cisplatin at escalating doses from 60 to 75 mg/m(2). Consolidation chemotherapy of pemetrexed 500 mg/m(2) was provided for 3 more 21-day cycles. Cisplatin doses were escalated as far as no more than 1/3 of the patients in a level developing dose limiting toxicities (DLT).

Results: Fifteen eligible patients were enrolled: nine in the first dose level and 3 in the second and third dose levels respectively. Two out of 9 patients in the first dose level experienced DLT (grade 3 esophagitis resulting in delay in treatment administration). The major serious acute toxicities were esophagitis (40%) and febrile neutropenia (20%). With a median follow up time of 22 months, median time to progression and overall survival has not been reached. The rate of survival at 24 months was 57.5% (95% CI: 27.5-87.4%) of the patients.

Conclusions: Three systemic dose levels of pemetrexed and cisplatin could be administered concurrently with radiotherapy. The rate of survival at 24 months was encouraging.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / physiopathology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Chemoradiotherapy*
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Consolidation Chemotherapy*
  • Disease Progression
  • Esophagitis / etiology
  • Female
  • Follow-Up Studies
  • Glutamates / administration & dosage
  • Glutamates / adverse effects
  • Guanine / administration & dosage
  • Guanine / adverse effects
  • Guanine / analogs & derivatives
  • Humans
  • Lung Neoplasms / pathology
  • Lung Neoplasms / physiopathology
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neutropenia / etiology
  • Pemetrexed
  • Survival Analysis

Substances

  • Glutamates
  • Pemetrexed
  • Guanine
  • Cisplatin