The clinical development of paclitaxel and the paclitaxel/carboplatin combination

• Published in: European journal of cancer (1990) Vol. 34; no. 10; pp. 1543 - 1548
• Main Authors: Schwartz, G.N., Pendyala, L., Kindler, H., Meropol, N., Perez, R., Raghavan, D., Creaven, P.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford Elsevier Ltd 01.09.1998; Elsevier
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; carboplatin; Carboplatin - administration & dosage; Carboplatin - adverse effects; Carcinoma, Non-Small-Cell Lung - drug therapy; Chemotherapy; Clinical Trials, Phase I as Topic; Dose-Response Relationship, Drug; Female; Humans; Lung Neoplasms - drug therapy; Male; Medical sciences; Middle Aged; neuropathy; non small cell lung cancer; paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; pharmacokinetics; Pharmacology. Drug treatments; pharmacokinetics; non small cell lung cancer; paclitaxel; neuropathy; carboplatin; Antineoplastic agent; Human; Drug combination; Chemotherapy; Treatment; Taxane derivatives; Paclitaxel; Carboplatin; Phase I trial; Malignant tumor; Platinum II Complexes
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/S0959-8049(98)00225-1

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/m 2, with a dose limiting toxicity of peripheral sensory neuropathy. Activity was seen in lung cancer, with a paclitaxel dose at or above 230 mg/m 2. 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.