Annals of Oncology 12:463-470, 2001
© 2001 European Society for Medical Oncology
research-article |
A multicenter randomized clinical trial comparing paclitaxel-cisplatin-etoposide versus cisplatin-etoposide as first-line treatment in patients with small-cell lung cancer
1Department of Medical Oncology, School of Medicine, University of Crete Greece
2First Department of Pulmonary Diseases, ‘Sotiria’ General Hospital of Athens Greece
3Department of Pulmonary Diseases, School of Medicine, University of Athens, ‘Sotiria’ General Hospital of Athens Greece
4Second Department of Pulmonary Diseases, ‘Stsmanoglion’ General Hospital of Athens Greece
5First Department of Medical Oncology, ‘Agios Savvas’ Anticancer Hospital of Athens Greece
6Department of Biostatistics, School of Medicine, University of Crete Greece
Correspondence to: D Mavroudis, MD, PhD Department of Medical Oncology University General Hospital of Herakhon PO Box 1352 71110 Heraklion, Crete Greec E-mail georgoul{at}med.uch.gr
Background Previous phase I-II studies have shown that the combination of paclitaxel-cisplatin-etoposide (TEP) is very active and well tolerated in patients with small-cell lung cancer (SCLC) In order to compare the TEP combination to cisplatin-etoposide (EP) regimen as front-line treatment in patients with SCLC, we conducted a randomised multicenter study
Patients and methodsOne hundred thirty-three chemotherapy-naive patients with histologically proven limited or extensive stage SCLC were randomised to receive either pacli-taxel 175 mg/m2 i v three-hour infusion on day 1 and cisplatin 80 mg/m2 i v on day 2 and etoposide 80 mg/m2 i v on days 2–4 with G-CSF support (5 mcg/kg s c days 5–15) or cisplatin 80 mg/m2 i v on day 1 and etoposide 120 mg/m2 i v on days 1–3 in cycles every twenty-eight days
ResultsDue to excessive toxicity and mortality observed in the TEP arm, an early interim analysis was performed and the study was closed Sixty-two patients received two hundred sixty-one cycles of TEP and seventy-one patients three hundred twenty-three cycles of EP The two patient groups were well balanced for age, sex, performance status, stage of disease and the presence of abnormal LDH at diagnosis In an intention-to-treat overall analysis both regimens were equally active with a complete and partial response rate of 50% (95% confidence interval (CI) 37 5%–62 4%) for TEP and 48% (95% CI 36 2%–59 5%) for EP (P = 0 8) The median time to disease progression was 11 months for TEP and 9 months for EP (P = 0.02). The duration of response, one-year survival and overall survival were similar in the two arms. Similarly, in an intention-to-treat subgroup analysis of patients with limited or extensive stage disease, there was no difference in the activity between the two regimens except of a longer median time to disease progression in the extensive stage in favour of the TEP regimen, eight versus six months (P = 0 04) However, there were eight toxic deaths in the TEP arm versus none in the EP arm (P = 0 001) Moreover, the TEP regimen was associated with more severe toxicity than the EP regimen in terms of grade 4 neutropenia (P = 0.04), grade 3–4 thrombocytopenia (P = 0 02), febrile neutropenia (P = 0 08), grade 3–4 diarrhea (P = 0.01), grade 3–4 asthenia (P = 0 05) and grade 3 neurotoxicity (P = 0 06)
Conclusions In this early terminated study, the TEP regimen was significantly more toxic than the EP regimen The TEP regimen is associated with significant toxicity and mortality, and should not be used outside of a protocol setting For future investigations, dose and schedule modifications are necessary to reduce toxicity
cisplatin, etoposide, paclitaxel, randomized trial, small-cell lung cancer
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