Περίληψη:
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 methods: One hundred thirty-three chemotherapy-naive
patients with histologically proven limited or extensive stage SCLC were
randomised to receive either paclitaxel 175 mg/m(2) i.v. three-hour
infusion on day 1 and cisplatin 80 mg/m(2) i.v. on day 2 and etoposide
80 mg/m(2) i.v. on days 2-4 with G-CSF support (5 mcg/kg s.c. days 5-15)
or cisplatin 80 mg/m(2) i.v. on day 1 and etoposide 120 mg/m(2) i.v. on
days 1-3 in cycles every twenty-eight days.
Results: Due 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.
Συγγραφείς:
Mavroudis, D
Papadakis, E
Veslemes, M
Tsiafaki, X and
Stavrakakis, J
Kouroussis, C
Kakolyris, S
Bania, E and
Jordanoglou, J
Agelidou, M
Vlachonicolis, J
Georgoulias, V
and Greek Lung Canc Cooperative Grp
