title: Weekly paclitaxel/cisplatin with concurrent radiotherapy in patients with locally advanced non-small cell lung cancer: a phase I study.
abstract: We designed a phase I study to determine the maximum tolerated doses of weekly cisplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (doses escalated alternately) when given concurrently with standard or hyperfractionated radiotherapy (RT) and to define the nature of the dose-limiting toxicity. Chemotherapy-naive patients with locally advanced non-small cell lung cancer received weekly combination cisplatin/paclitaxel with concurrent local RT. Radiation therapy was initially given at the dose of 1.2 Gy twice daily x 5 d/wk x 5 weeks (total dose, 60 Gy). In the last two patient cohorts, the single daily dose was decreased to 2 Gy x 5 d/wk x 6 weeks. Overall, 25 patients were recruited into five different cohorts. Esophagitis was the main nonhematologic toxicity, occurring in 16 of 25 patients (64%; grade 3 or 4 in five). Neutropenia was the most prevalent hematologic toxicity, occurring in 33 of 141 weekly courses, but grade 4 neutropenia was seen in only four courses. Cisplatin/paclitaxel doses of 35 mg/m2/wk and 45 mg/m2/wk, respectively, were safe when standard RT was used, while the cisplatin dose had to be decreased to 30 mg/m2/wk in patients receiving bifractionation. Two complete and 13 partial responses were observed, for a 60% overall response rate (95% confidence interval, 39% to 79%). Median survival was 16 months, with a 66% 1-year actuarial probability. We thus conclude that the cisplatin/paclitaxel combination given weekly can be safely administered concurrent with both standard or hyperfractionated RT. Hyperfractionation is associated with a higher incidence of severe esophagitis and required a slight reduction in cisplatin dose. To verify whether the use of a daily schedule translates into a better therapeutic index, a new phase I study is under way, testing twice-daily cisplatin/paclitaxel concurrently with hyperfractionated RT.
authors.affiliation: Department of Radiation Therapy, and Radiology, National Tumor Institute, Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Comella
authors.forename: G
authors.initials: G
authors.lastname: Frasci
authors.forename: G
authors.initials: G
authors.lastname: Scoppa
authors.forename: C
authors.initials: C
authors.lastname: Guida
authors.forename: A
authors.initials: A
authors.lastname: Gravina
authors.forename: F
authors.initials: F
authors.lastname: Fiore
authors.forename: R
authors.initials: R
authors.lastname: Casaretti
authors.forename: A
authors.initials: A
authors.lastname: Daponte
authors.forename: P
authors.initials: P
authors.lastname: Ruffolo
authors.forename: P
authors.initials: P
authors.lastname: Comella
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage*; D011879:Radiotherapy Dosage; D016019:Survival Analysis
chemical_list: D017239:Paclitaxel; D002945:Cisplatin