Treatment-related deaths in small cell lung cancer trials: can patients at risk be identified? Medical Research Council Lung Cancer Working Party

Lung Cancer. 1994 Sep;11(3-4):259-74. doi: 10.1016/0169-5002(94)90546-0.

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 < or = 50 (translated as a WHO performance grade (PS) > or = 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 > or = 10,000/mm3 (this variable was not tested by Radford), and changing the other categories to WHO PS > or = 2 (KP < or = 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.

Publication types

  • Comparative Study
  • Meta-Analysis

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Carcinoma, Small Cell / mortality*
  • Carcinoma, Small Cell / therapy*
  • Clinical Trials, Phase II as Topic
  • Combined Modality Therapy
  • Humans
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / therapy*
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Radiotherapy / adverse effects
  • Randomized Controlled Trials as Topic / adverse effects*
  • Risk Factors
  • Surgical Procedures, Operative / adverse effects