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Toxicity report of a phase 1/2 dose-escalation study in patients with inoperable, locally advanced nonsmall cell lung cancer with helical tomotherapy and concurrent chemotherapy

  1. Samuel Bral MD1,†,*,
  2. Michaël Duchateau MSc1,
  3. Harijati Versmessen MD1,
  4. Douwe Verdries MD2,
  5. Benedikt Engels MD1,
  6. Mark De Ridder MD, PhD1,
  7. Koen Tournel MSc1,
  8. Christine Collen MD1,
  9. Hendrik Everaert MD, PhD3,
  10. Denis Schallier MD, PhD4,
  11. Jacques De Greve MD, PhD4,
  12. Guy Storme MD, PhD1

Article first published online: 13 NOV 2009

DOI: 10.1002/cncr.24732

Issue

Cancer

Cancer

Volume 116, Issue 1, pages 241–250, 1 January 2010

Additional Information

How to Cite

Bral, S., Duchateau, M., Versmessen, H., Verdries, D., Engels, B., Ridder, M. D., Tournel, K., Collen, C., Everaert, H., Schallier, D., De Greve, J. and Storme, G. (2010), Toxicity report of a phase 1/2 dose-escalation study in patients with inoperable, locally advanced nonsmall cell lung cancer with helical tomotherapy and concurrent chemotherapy. Cancer, 116: 241–250. doi: 10.1002/cncr.24732

Author Information

  1. 1

    Department of Radiation Oncology, Oncology Center, Brussels University Hospital, Brussels, Belgium

  2. 2

    Department of Radiology, Oncology Center, Brussels University Hospital, Brussels, Belgium

  3. 3

    Department of Nuclear Medicine, Oncology Center, Brussels University Hospital, Brussels, Belgium

  4. 4

    Department of Medical Oncology, Oncology Center, Brussels University Hospital, Brussels, Belgium

  1. †

    Fax: (011) 32 2 477 5450

*Department of Radiation Oncology, Oncologisch Centrum, Universitair Ziekenhuis, Laarbeeklaan 101, Brussels 1090 Belgium

Publication History

  1. Issue published online: 11 JAN 2010
  2. Article first published online: 13 NOV 2009
  3. Manuscript Accepted: 4 MAY 2009
  4. Manuscript Revised: 20 APR 2009
  5. Manuscript Received: 30 JAN 2009

Funded by

  • “Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (FWO),”. Grant Numbers: G.0486.06, G.0412.08
  • “Wetenschappelijk fonds Willy Gepts”
  • Sanofi-Aventis

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Keywords:

  • lung cancer;
  • chemoradiation;
  • dose escalation;
  • intensity-modulated radiotherapy;
  • image-guided radiotherapy

In this phase 1/2 trial, the authors assessed the possibility of radiation dose escalation using helical tomotherapy in a concurrent approach for unselected patients with inoperable, locally advanced nonsmall cell lung cancer. The maximum tolerated dose was set at 67.2 grays, and cisplatin/docetaxel was given weekly, resulting in an acceptable acute and late toxicity profile with a 61% response rate.

Abstract

BACKGROUND:

The objective of the current study was to evaluate the feasibility and toxicity of radiation dose escalation with concurrent chemotherapy using helical tomotherapy (HT) in patients with inoperable, locally advanced, stage III nonsmall cell lung cancer (LANSCLC) (grading determined according to the American Joint Committee on Cancer 6th edition grading system).

METHODS:

This phase 1/2 study was designed to determine the maximum tolerated dose (MTD) of radiotherapy in patients with LANSCLC administered concurrently with docetaxel and cisplatin. Radiotherapy was delivered using HT. A dose per fraction escalation was applied starting at 2 grays (Gy), with an increase of 6% per dose cohort (DC). The Radiation Therapy Oncology Group acute radiation morbidity score was used to monitor pulmonary, esophageal, and cardiac toxicity.

RESULTS:

Dose escalation was performed in 34 patients over 5 DCs to a dose per fraction of 2.48 Gy. No differences were observed in acute toxicity between the different DCs. However, a significant increase in late lung toxicity in DC IV, which received a fraction size of 2.36 Gy, necessitated a halt in further dose escalation with the MTD defined as 2.24 Gy per fraction. The overall incidence of acute grade ≥3 esophageal and pulmonary toxicity was 24% and 3%, respectively (grading determined according to the Radiation Therapy Oncology Group-European Organisation for Research and Treatment of Cancer toxicity scoring system). The overall incidence of late lung toxicity was 21%, but the incidence was an acceptable 13% in DCs I, II, and III. The local response rate was 61% on computed tomography images.

CONCLUSIONS:

The use of HT to 67.2 Gy with concurrent cisplatin/docetaxel was feasible and resulted in acceptable toxicity. A full phase 2 study has been initiated to establish the true local response rate at the MTD of 2.24 Gy per fraction. Cancer 2010. © 2010 American Cancer Society.

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