The clinical development of paclitaxel and the paclitaxel/carboplatin combination.
Paclitaxel and carboplatin have nonoverlapping toxicities with a broad range of clinical activity. The combination of escalating dose paclitaxel and carboplatin dosed to a fixed area under the curve (AUC) was explored in a series of phase I studies. 76 patients were treated with paclitaxel over three hours followed by a 30 min carboplatin infusion, dosed by the Calvert formula to a target AUC of 4.0 or 4.5 mg/min/ml-1. The maximum tolerated dose of paclitaxel was 270 to 290 mg/m2, with a dose limiting toxicity of peripheral sensory neuropathy. Activity was seen in lung cancer, with a paclitaxel dose at or above 230 mg/m2. Neuropathy correlated with paclitaxel AUC due to nonlinear pharmacokinetics at higher doses. Ongoing studies include the use of amifostine as a neuroprotectant and phase II studies of the paclitaxel/carboplatin regimen in head and neck cancer, small cell lung cancer and sarcomas.
Schwartz
G N
GN
Department of Solid Tumour Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Pendyala
L
L
Kindler
H
H
Meropol
N
N
Perez
R
R
Raghavan
D
D
Creaven
P
P
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D017321:Clinical Trials, Phase I as Topic; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects
D016190:Carboplatin; D017239:Paclitaxel