Validation of standard definition of sensitive versus refractory relapsed small cell lung cancer: a pooled analysis of topotecan second-line trials.

BACKGROUND: Relapsed small cell lung cancer (SCLC) is classified into sensitive or resistant according to treatment-free interval (TFI) longer or shorter than 60 (criteria 1) or 90 (criteria 2) days. However, these criteria are based on small old studies and are inconsistent among different studies. The present study aimed at validating these criteria and assessing additional clinical parameters predictive of response rate (RR) and overall survival (OS).

PATIENTS AND METHODS: A database of six GlaxoSmithKline-sponsored trials of intravenous topotecan-based second-line chemotherapy was analysed. Validation of sensitive/resistant definition was performed on the entire dataset (631 patients), while study of additional parameters and development of prognostic model was conducted dividing the database into derivation and validation sets.

RESULTS: The association between criterion 1 or 2 and RR was confirmed. Changing TFI cut-off or adding response to first-line did not improve accuracy. In addition to TFI (P=0.007), only presence of liver metastasis (P=0.046) was found to affect the probability of objective response. TFI, age, liver metastases, performance status (PS), albumin, haemoglobin and sodium levels were identified as independent prognostic factors for OS. A prognostic model, based on these variables, was able to separate relapsed SCLC into low versus high risk categories (median OS 41.4 versus 20.0 weeks).

CONCLUSIONS: This study confirms the value of standard criteria for relapsed SCLC outcome prediction. Patients with TFI<60 days are refractory to second-line chemotherapy and have poor OS. Patients with liver metastasis and/or PS2 and/or low albumin, regardless of TFI, have similarly poor outcome.