M. Bakker et al., PHASE-I STUDY OF HIGH-DOSE EPIRUBICIN AND VINORELBINE IN PREVIOUSLY UNTREATED NON-SMALL-CELL LUNG-CANCER STAGE IIIB-IV, British Journal of Cancer, 72(6), 1995, pp. 1547-1550
The aim of the study was to determine the maximum tolerated dose (MTD)
for the combination of high-dose epirubicin and vinorelbine in chemot
herapy-naive patients with inoperable non-small-cell lung cancer (NSCL
C). Twenty-one patients with stage IIIB and IV NSCLC were treated in a
single-centre study with escalating doses of epirubicin and vinorelbi
ne given on an outpatient basis. The first dose level comprised epirub
icin 100 mg m(-2) on day 1 and vinorelbine 20 mg m(-2) (days 1 and 8)
given intravenously every 3 weeks. Escalating doses for epirubicin and
vinorelbine were respectively 120 (day 1) and 20 (days 1 and 8), 120
(day 1) and 25 (days 1 and 8) and 135 (day 1) and 25 (days 1 and 8) mg
m(-2). Inclusion criteria were age less than or equal to 75 years, EC
OG performance score less than or equal to 2 and normal renal, hepatic
and bone marrow functions. Dose-limiting toxicities were thrombocytop
enia grade II and neutropenia grade III on day 8, febrile neutropenia,
and neutropenia lasting >7 days. No dose-limiting toxicity (DLT) was
observed at the first dose level; at the 135/25 mg m(-2) dose level th
ree out of six patients had a DLT which was considered as unacceptable
. The only non-haematological toxicity reaching grade III was nausea/v
omiting. One patient showed cardiac toxicity. No neurotoxicity and no
treatment-related deaths were seen. The maximum tolerated dose of epir
ubicin and vinorelbine is 135 mg m(-2) (day 1) and 25 mg m(-2) (days 1
and 8) respectively, causing mainly haematological toxicity. The reco
mmended dose of epirubicin and vinorelbine for phase II studies is fou
nd to be 120 mg m and 20 mg m(-2) respectively.