Phase II and pharmacologic study of weekly oral paclitaxel plus cyclosporine in patients with advanced non-small-cell lung cancer.
OBJECTIVE
A phase II study was performed to assess the efficacy and toxicity of oral cyclosporine (CsA) plus paclitaxel in advanced non-small-cell lung cancer (NSCLC).


METHODS
Chemotherapy-naive or previously treated patients (one regimen) with measurable disease and World Health Organization performance status <or= 2 were eligible. Oral paclitaxel was given weekly in a dose of 90 mg/m(2) bid. CsA (10 mg/kg) was given 30 minutes before each dose of oral paclitaxel.


RESULTS
Twenty-six patients with a median age of 54 years (range, 32 to 77 years) were entered onto this study. Eighteen patients (69%) had received one prior chemotherapy regimen. The most frequently recorded toxicities were as follows: National Cancer Institute common toxicity criteria grade 3 neutropenia, eight patients (31%); grade 4, six patients (23%); grade 4 febrile neutropenia, three patients (12%); grade 2/3 neurotoxicity, three patients (12%); and grade 2 nail changes, four patients (15%). The overall response rate (ORR) of the 23 assessable patients was 26% (95% confidence interval [CI], 10% to 48%). In the intention-to-treat population, the ORR was 23% (95% CI, 9% to 44%). The median time to progression was 3.5 months (95% CI, 1.2 to 3.9 months), and median overall survival was 6.0 months (95% CI, 2.3 months to not available). Pharmacokinetics revealed that the mean area under the concentration-time curve (AUC) of oral paclitaxel was 5.0 +/- 2.3 micro mol/L/h in week 1 and 4.6 +/- 2.0 micro mol/L/h in week 2, with interpatient variabilities (coefficient of variation [%CV]) of 45% and 42%, respectively. The intrapatient variability (%CV) of the AUC was 14.5%.


CONCLUSIONS
Oral paclitaxel plus CsA is active and safe in advanced NSCLC, including in patients previously treated with chemotherapy.
Kruijtzer
C M F
CM
Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Schellens
J H M
JH
Mezger
J
J
Scheulen
M E
ME
Keilholz
U
U
Beijnen
J H
JH
Rosing
H
H
Mathôt
R A A
RA
Marcus
S
S
van Tinteren
H
H
Baas
P
P
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D017239:Paclitaxel