The prognostic value of etoposide area under the curve (AUC) at first chemotherapy cycle in small cell lung cancer patients: a multicenter study of the groupe Lyon-Saint-Etienne d'Oncologie Thoracique (GLOT)

Purpose: To assess the potential relationships between systemic exposure to doxorubicin, etoposide and ifosfamide at first chemotherapy cycle and ther apeutic effect, tumor response. toxicity. and survival. in small cell lung cancer (SCLC) patients. Patients and methods: Twenty-four patients referred to five different centers with either thorax-limited or metastatic SCLC en tered the study. All but one received two induction courses of the 3 day-AV I (doxorubicin 50 mg/m(2) day 1. etoposide 120 mg/m(2) day 1, 2, 3, ifosfam ide 2000 mg/m(2) day 1, 2) regimen. Individual plasma samples were collecte d at the first course and complete concentration data on 24 courses were av ailable. Drugs exposures were estimated using a population pharmacokinetic method and expressed as clearance (Cl), area under the curve (AUC). and AUC -intensity (AUC/cycle duration). Responding patients received thoracic irra diation + concomitant cisplatinum-etoposide (limited disease) or Four more courses of AVI (extensive disease). The impact of exposure parameters on ha ematological toxicity, tumor response and overall survival was assessed usi ng linear regression, the Mann-Whitney U-test and the log-rank test, Kaplan Meier estimation. respectively. Results: Twenty-three patients could be ev aluated for response and survival. We found no relationship between drug ex posure and haematological toxicity but all patients had received Granulocyt e-Colony Stimulating Factor support. Tumor response was marginally influenc ed by ifosfamide: AUG. In patients with etoposide AUC > 254.8 mg h/l. I-yea r survival was 50.0 vs. 9.1% in the other group (median 11.4 vs. 7.1 months , P = 0.02), with respect to established prognostic factors. In patients wi th extensive disease only (n = 15), 1-year survival was 42.9 vs. 0% (median 11.3 vs. 5.3 months. P = 0.01). Conclusion: This: study strongly suggests that SCLC patients should benefit from sufficient etoposide exposure at fir st cycle to improve survival. Adaptative control based on plasma concentrat ion measurements should be tested in further studies assessing various poly chemotherapy regimens. (C) 2001 Elsevier Science ireland Ltd. All rights re served.