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In Reply:

National Cancer Institute of Canada Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada

In the National Cancer Institute of Canada Clinical Trials Group BR.20,¹ we reported that maintenance vandetanib, a molecularly targeted antagonist of the vascular endothelial growth factor (VEGF) receptor and the epidermal growth factor receptor, was not effective when given after primary therapy with chemotherapy ± radiation.

Although we agree with Artac and Bozcuk that the debate about maintenance chemotherapy for small-cell lung cancer is not over, that question was not addressed in the design of BR.20. However, we note that Artac and Bozcuk comment on two trials in which etoposide and cisplatin were administered after an initial anthracycline-containing regimen. In small-cell lung cancer, a platinum-containing regimen is generally regarded as superior therapy. When a platinum-containing regimen is used after administration of an inferior regimen, it is likely that the small impact on survival is due to additional active killing of cancer cells rather than true maintenance of the status quo.

Artac and Bozcuk also comment on the minor imbalance in patients in our study who received additional anticancer therapy after progression. Although we agree that effective salvage therapy given after progressive disease may influence overall survival, this was a phase II trial with only 107 patients; small differences in patient numbers may show relatively large numeric differences in percentage. To examine this, we performed an exploratory analysis and demonstrated that the conclusion remains unchanged after adjusting for salvage therapy.

We note that in many trials of VEGF/VEGF receptor inhibitors, the inhibitor is administered concurrently with chemotherapy and then continued after chemotherapy as single-agent maintenance therapy. There is no evidence from our study to support or refute the hypothesis that concurrent administration of vandetanib with etoposide and cisplatin would prolong progression-free and overall survival. Such studies may be of interest.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment or Leadership Position: None Consultant or Advisory Role: None Stock Ownership: Lesley Seymour, AstraZeneca Honoraria: None Research Funding: Lesley Seymour, to NCIC CTG, AstraZeneca, Expert Testimony: None Other Remuneration: None

REFERENCE

1. Arnold AM, Seymour L, Smylie M, et al: Phase II study of vandetanib or placebo in small cell lung cancer patients after complete or partial response to induction chemotherapy with or without radiation therapy: National Cancer Institute of Canada Clinical Trials Group Study BR.20. J Clin Oncol 25:4278-4284, 2007[Abstract/Free Full Text]

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Related Correspondence

• The Debate About Maintenance Is Not Over in Small-Cell Lung Cancer
  Mehmet Artac and Hakan Bozcuk
  JCO 2007 25: 5840 [Full Text]

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