Treatment-related deaths in small cell lung cancer trials: can patients at risk be identified?

Abstract

Objectives: This paper investigates the problem of treatment-related deaths in small cell lung cancer (SCLC). Design: To observe and define increased hazard levels, and to identify factors relating to these excess deaths. Setting: The United Kingdom. Subjects: A total of 2196 patients entered into the series of six randomised clinical trials in SCLC conducted by the Medical Research Council (MRC) Lung Cancer Working Party (LCWP). Results: In this large series of patients an increased risk of death in the second week after commencing the first cycle of chemotherapy was observed, suggesting that of the 10% of patients who died within 3 weeks of starting chemotherapy, half may have been treatment-related. Much less additional risk was associated with subsequent cycles of chemotherapy, and no additional risk with either initial surgery or radiotherapy. Radford et al. [Eur J Cancer 1993; 29A: 81–86] suggested that the risk factors for death from sepsis were a Karnofsky Performance (KP) score of ≤ 50 (translated as a WHO performance grade (PS) ≥ 3), age > 50 years and three or more drugs in the chemotherapy regimen utilised. Starting with this model we found that our data suggest it can be refined by omitting age and including a white blood cell count ≥ 10 000/mm 3 (this variable was not tested by Radford), and changing the other categories to WHO PS ≥ 2 (KP ≤ 70), and four or more drugs. Within our data this revised model identified a high risk group of patients with an excess death rate of more than 15% in the second week after starting chemotherapy. Radford et als' suggestion that high risk patients be given half doses of drugs at the first cycle should be tested in a randomised clinical trial.