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In Reply:

Centre Hospitalier Universitaire, Montpellier, France

Our randomized, double-blind, placebo-controlled, phase III study aimed at determining whether thalidomide prolongs survival of patients with extensive-disease small-cell lung cancer.¹ The hypothesis was that a 20% improvement could be achieved in the chemotherapy plus thalidomide group in comparison with the chemotherapy plus placebo group. The survival rate at 7 months after random assignment has been considered in order to calculate the planned accrual taking into account the aforementioned hypothesis. This specific landmark time took place, in fact, 9 months after the start of therapy (and corresponded to the usual median survival for extensive-disease small-cell lung cancer). As stated in the Statistical Considerations section, patients were randomly assigned at the end of step one (induction chemotherapy). The hypothesis was calculated taking into account data observed in the four-drug regimen group of our previous phase III, randomized study comparing two- versus four-drug regimens.² In order to take into account Dr Rossi’s query, we report the 7-month overall survival as 69.8% and 81.6% in the placebo and thalidomide groups, respectively. From a methodological point of view, it is well recognized that the survival difference observed at a given time of survival curve is not a reliable indicator. This is why we highlighted the hazard ratio as the main result (0.74; 95% CI, 0.49 to 1.12; P = .16). This result supports the conclusion of our study that "treatment with thalidomide was not associated with a significant improvement in survival of small-cell lung cancer patients" insofar as neither overall, nor progression-free survivals significantly differ.

Proportions of patients with performance status of 2 were well balanced between the two groups (14% and 12% in the placebo and thalidomide groups, respectively). Therefore, this variable cannot be considered as a putative bias in the global result.

The slow accrual in this clinical trial could have different explanations, among them is the fact that clinical trials using intensive chemotherapy in small-cell lung cancer are difficult to conduct.³

Both the study by Lee et al⁴ and the study reported by us¹ have produced congruent results: no benefit was observed when thalidomide was combined with chemotherapy in small-cell lung cancer. The designs were different. In the former study, low doses of thalidomide were administered concomitantly with the start of standard doublet chemotherapy. In the French study, higher doses of thalidomide were combined with a dose-dense chemotherapy in responder patients only. As accurately observed by Dr Rossi, both strategies have failed. Considering that this is a "tombstone" for all targeted therapies beyond thalidomide is a respectable opinion. However, despite recent efforts in improving induction chemotherapy, small-cell lung cancer clinically behaves aggressively with a rapid growth and metastatic spread. As both features are thought to be angiogenesis-dependent processes, therapy targeting angiogenesis could be considered as a potential new approach and new antiangiogenic therapies might be promising.

AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Pujol JL, Breton JL, Gervais R, et al: Phase III double-blind, placebo-controlled study of thalidomide in extensive-disease small-cell lung cancer after response to chemotherapy: An intergroup study FNCLCC cleo04-IFCT 00-01. J Clin Oncol 25:3945-3951, 2007[Abstract/Free Full Text]

2. Pujol JL, Daurès JP, Rivère A, et al: Etoposide plus cisplatin with or without the combination of 4'-epidoxorubicin and cyclophosphamide in the treatment of extensive stage small cell lung cancer. A FNCLCC* multicentre phase III randomised study. J Natl Cancer Inst 93:300-308, 2001[Abstract/Free Full Text]

3. Trillet-Lenoir V, Piedbois P, Buyse M: The role of colony stimulating factors in small cell lung cancer: Why the question is still unsolved. Lung Cancer 37:125-126, 2002[CrossRef][Medline]

4. Lee SM, Woll PJ, James LE, et al: A phase III randomised, double blind, placebo controlled trial of etoposide/carboplatin with or without thalidomide in advanced small cell lung cancer (SCLC). J Thor Oncol 2:S306-S307 (suppl 4: abstr PRS-04), 2007

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Related Correspondence

• Thalidomide in Small-Cell Lung Cancer: Is It a Tombstone?
  Antonio Rossi, Cesare Gridelli, and Emilio Bria
  JCO 2008 26: 160 [Full Text]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Pujol, J. L. Search for Related Content PubMed Articles by Pujol, J. L. Related Articles Related Correspondence Social Bookmarking                            What's this?