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Toxicity predicts effective chemotherapy dose

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Toxicity from chemotherapy in lung cancer patients could help predict treatment efficacy, according to research in the September issue of THE LANCET ONCOLOGY [1].

Chemotherapy is standard treatment for patients with advanced non-small cell lung cancer, although benefits are modest and toxicity substantial. Dr Massimo Di Maio and colleagues hypothesised that neutropenia, a haematological toxicity, could be a predictor of drug activity and treatment efficacy.

They analysed overall survival of 1265 patients with non-small cell lung cancer who had received chemotherapy within three phase III randomised trials. In a subgroup of 436 patients, who had received 6 cycles and were alive 180 days after randomisation, overall survival was increased from 31.4 weeks for those without neutropenia to over 40 weeks for those experiencing either mild or severe neutropenia. The risk of death was also reduced by about a third for those who had neutropenia. Findings were much the same for the group as a whole.

Dr Di Maio (National Cancer Institute, Naples, Italy) states "Neutropenia during chemotherapy is associated with increased survival of patients with advanced non-small cell lung cancer, and its absence might be the result of underdosing. Prospective trials are needed to assess whether drug dosing guided by the occurrence of toxic effects could improve efficacy of standard regimens".

"Inadvertent underdosing of chemotherapy is probably a lot more common than we think", says Dr Howard Gurney (University of Sydney, Australia) in an accompanying commentary [2]. "It is not about inducing toxic effects for the sake of it - it is about getting the right dose", he concludes.


Notes to editors

[1] Lancet Oncol 2005; 6: 669-77.

[2] Lancet Oncol 2005; 6: 637.

Contact: Dr Cesare Gridelli, Unita Operativa Sperimentazioni Cliniche, Istituto Nazionale Tumori, via M Semmola, I-80131 Napoli, Italy.

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