N. Levitan et al., Multi-institutional phase I/II trial of paclitaxel, cisplatin, and etoposide with concurrent radiation for limited-stage small-cell lung carcinoma, J CL ONCOL, 18(5), 2000, pp. 1102-1109
Purpose: To determine the feasibility of adding paclitaxel to standard cisp
latin/etoposide (EP) and thoracic radiotherapy.
Patients and Methods: Thirty-one patients were enrolled onto this study. Du
ring the phase I section of this study, the dose of paclitaxel was escalate
d in groups of three or more patients. Cycles were repeated every 21 days.
For cycles 1 and 2, paclitaxel was administered according to the dose-escal
ation schema at doses of 100, 135, or 170 mg/m(2) intravenously over 3 hour
s on day I. Once the maximum-tolerated dose (MTD) of paclitaxel (for cycles
1 and 2, concurrent with radiation) was determined, that dose was used in
all subsequent patients entered onto the phase II section of this study, fo
r cycles 3 and 4, the paclitaxel dose was fixed at 170 mg/m(2) in all patie
nts. On day 2, cisplatin 60 mg/m(2) was administered for all cycles. On day
s 1, 2, and 3, etoposide 60 mg/m(2)/d (cycles 1 and 2) or 80 mg/m(2)/d (cyc
les 3 and 4) wets administered. Chest radiation was given at 9 Gy/wk in fiv
e fractions for 5 weeks beginning on day 1 of cycle 1. Granulocyte colony-s
timulating factors were used during cycles 3 and 4 only.
Results: Twenty-eight patients were assessable. The MTD of paclitaxel war 1
35 mg/m(2), with the dose-limiting toxicity being grade 4 neutropenia. Cycl
es 1 and 2 were associated with grade 4 neutropenia in 32% of courses, with
fever occurring in 7% of courses and grade 2/3 esophagitis in 13%. Cycles
3 and 4 were complicated by grade 4 neutropenia in 20% of courses, with fev
er occurring in 6% of courses and grade 2/3 esophagitis in 16%. The overall
response rate war 96% (complete responses, 39%; partial responses, 57%). A
fter a median follow-up period of 23 months (range, 9 to 40 months), the me
dian survival time was 22.3 months (95% confidence interval, 15.1 to 34.3 m
onths).
Conclusion: The MTD of paclitaxel with radiation and EP treatment is 135 mg
/m(2) given over 3 hours. In this schedule of administration, a high respon
se rate and acceptable toxicity can be anticipated. J Clin Oncol 18:1102-11
09. (C) 2000 by American Society of Clinical Oncology.