title: Fractionated administration of carboplatin/paclitaxel reduces neurotoxicity in patients with advanced non-small cell lung cancer.
abstract: The combination of carboplatin/paclitaxel is commonly used as chemotherapy for advanced non-small cell lung cancer. However, the relatively high incidence of neurotoxicity remains a problem. This study was undertaken to determine whether the fractionated administration regimen can reduce the neurotoxicity. Patients with stage III or IV non-small cell lung cancer were randomized to the nonfractionated (NF) dose group, which received paclitaxel (200 mg/m(2)) and carboplatin (area under the concentration-time curve=6) on day 1, or the fractionated dose (F) group, which received paclitaxel (100 mg/m(2)) and carboplatin (area under the concentration-time curve=3) on days 1 and 8. The cycle was repeated every 3 weeks. Peripheral neuropathy was objectively evaluated by measuring the current perception threshold (CPT) in the median nerve using a neurometer. Fourteen and 13 patients were assigned to the NF and F groups, respectively. The incidence of subjective numbness was significantly lower in the F group (15.4%) than in the NF group (57.1%). The CPT value determined at 2000 Hz showed significant increases in the NF group compared with the pretreatment baseline, but no significant changes were observed in the F group. The response rate was comparable in both groups. The fractionated administration of carboplatin/paclitaxel combination therapy showed a significant reduction in neurotoxicity. Measurement of CPT by a neurometer is a useful tool to evaluate the neurotoxicity of anticancer drugs objectively.
authors.affiliation: Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan. ishiiysk@dokkyomed.ac.jp
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Ishii
authors.forename: Sakae
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Kazumi
authors.initials: K
authors.lastname: Okazaki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyoshi
authors.forename: Tomoe
authors.initials: T
authors.lastname: Furihata
authors.forename: Isano
authors.initials: I
authors.lastname: Hase
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takizawa
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kikkawa
authors.forename: Issei
authors.initials: I
authors.lastname: Yamada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukuda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy / Q000379:methods; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D020258:Neurotoxicity Syndromes / Q000517:prevention & control; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D010523:Peripheral Nervous System Diseases / Q000517:prevention & control; D016019:Survival Analysis
chemical_list: D016190:Carboplatin; D017239:Paclitaxel