Thoracic radiation therapy and concomitant low-dose daily paclitaxel in non-small cell lung cancer: a phase I study.
The primary objective of the current study was to determine the maximum tolerated dose of paclitaxel (PTX) that could be added daily to radiation therapy (RT) in patients with non-small cell lung cancer (NSCLC). The secondary objective was to achieve a plasma concentration of PTX estimated to exert a radiosensitizing effect. Eighteen patients with locally advanced NSCLC were treated. 60 Gy of RT were given in 2 Gy fractions, 5 days per week. A daily dose of PTX was delivered by 4-h i.v. infusion before RT. The initial dose level of PTX was 9 mg/m2/day, escalated by 1 mg at each additional patient triplet. Two out of 6 patients experienced acute dose limiting toxicity (DLT) at the 12 mg/m2/day PTX dose level. PTX continuously greater than 10 nM, the estimated radiosensitizing condition, was achieved at the PTX dose level of 12 mg/m2/day. PTX at doses up to 11 mg/m2/day may be safely added to a conventional conformal RT course. Both DLT and the estimated radiosensitizing plasma exposure to PTX were encountered at the 12 mg/m(2)/day dose level.
Gobitti
Carlo
C
Radiation Oncology Department, Centro di Riferimento Oncologico, National Cancer Institute, 33081 Aviano, Italy. cgobitti@cro.it
Franchin
Giovanni
G
Minatel
Emilio
E
Gigante
Marco
M
Basso
Barbara
B
Bujor
Laurentiu
L
Trovò
Mauro G
MG
D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002851:Chromatography, High Pressure Liquid; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D016019:Survival Analysis; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel