Fast track — ArticlesChemotherapy-induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer: a pooled analysis of three randomised trials
Introduction
Most patients diagnosed with advanced non-small-cell lung cancer are offered chemotherapy on the basis of studies that showed a small but significant survival advantage in adults,1 including elderly people.2 At present, a two-drug regimen consisting of a platinum agent is regarded standard treatment for adults with good performance status,3, 4 resulting in a median survival of about 8 months, and about 35% of patients alive at 1 year. However, the toxic effects of such treatment can be substantial, and vary with the drug that is added to cisplatin or carboplatin (usually vinorelbine, gemcitabine, or a taxane).5 For patients aged older than 70 years, no reliable data have shown that combination chemotherapy is more effective than a single agent, with vinorelbine2 or gemcitabine6 producing the most convincing results. Overall, although the efficacy of chemotherapy is modest at best, cytotoxic drugs will probably continue to be part of standard treatment of non-small-cell lung cancer in the next few decades.
Haematological toxic effects caused by most cytotoxic drugs could be a biological measure of drug activity and might predict treatment efficacy.7, 8 Studies9, 10, 11, 12 of adjuvant chemotherapy for breast cancer have shown that patients who have increased toxic effects during treatment had a better outcome than did those who had no, or less severe, toxic effects. However, the predictive (ie, estimation of the chance of benefit from chemotherapy) or prognostic (ie, estimation of the chance of survival) role of chemotherapy-induced neutropenia in advanced non-small-cell lung cancer have not been established. Thus, we reviewed data for three randomised phase III trials2, 6, 13 of chemotherapy in advanced non-small-cell lung cancer to assess whether chemotherapy-induced neutropenia was associated with increased survival. This analysis was not planned at the time of trials, but was prompted by independent evidence in scientific publications.
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Patients and treatments
Patients with advanced non-small-cell lung cancer who participated in three randomised clinical trials2, 6, 13 done by the same cooperative group of Italian institutions coordinated by the Clinical Trials Unit of the National Cancer Institute, Naples, Italy, between 1996 and 2001 were selected for this study (figure 1). All three studies were approved by ethics committees, and all patients gave written informed consent. The three protocols included patients with stage IV or IIIB disease (with
Results
Figure 1 shows the study profile. Figure 2 shows the worst grade of neutropenia recorded at each cycle of chemotherapy in the 1265 patients analysed. 484 patients received six cycles of chemotherapy, 436 of whom were alive 180 days after randomisation and thus included in the landmark group.
Table 1 shows characteristics of patients in the landmark analysis. Median age was 71 years (range 36–84). Most patients were men, had a good performance status (ie, 0–1), and had metastatic disease.
Table 2
Discussion
We have shown that the presence, but not severity, of chemotherapy-induced neutropenia were prognostic for increased survival. The difference in survival for patients according to whether they had neutropenia was significant, and was similar to, and perhaps even greater than, that of the overall advantage attributed to platinum-based chemotherapy compared with supportive-care alone.1 Importantly, results should not be biased by the use of G-CSF because the protocols stipulated no prophylactic
References (26)
- et al.
Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial. Scandinavian Breast Group 9401 study
Lancet
(2000) Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials
BMJ
(1995)Effects of vinorelbine on quality of life and survival of elderly patients with advanced non small cell lung cancer
J Natl Cancer Inst
(1999)- et al.
Benefits of adding a drug to a single-agent or a 2-agent chemotherapy regimen in advanced non-small-cell lung cancer: a meta-analysis
JAMA
(2004) - et al.
American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003
J Clin Oncol
(2004) - et al.
Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer
N Engl J Med
(2002) - et al.
Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung cancer in the Elderly Study (MILES) phase III randomized trial
J Natl Cancer Inst
(2003) The leucocyte nadir, a predictor of chemotherapy efficacy?
Br J Cancer
(1999)How to calculate the dose of chemotherapy
Br J Cancer
(2002)- et al.
Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer
Br J Cancer
(1997)
Leucocyte nadir as a marker for chemotherapy efficacy in node-positive breast cancer treated with adjuvant CMF
Br J Cancer
Analysis of the prognostic effects of inclusion in a clinical trial and of myelosuppression on survival after adjuvant chemotherapy for breast carcinoma
Cancer
Moderate neutropenia with adjuvant CMF confers improved survival in early breast cancer
Br J Cancer
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