title: Simultaneous radiochemotherapy with paclitaxel in non-small cell lung cancer: a clinical phase I study.
abstract: Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of the most active single agents available for the treatment of non-small cell lung cancer (NSCLC), with reported response rates of 21% to 24%. Its observed radiosensitizing effect is attributed to its interruption of cell development at the G2/M phase of the cell cycle, when cells are most sensitive to the killing effects of ionizing radiation. This phase I study of paclitaxel and simultaneous radiation therapy in patients with previously untreated, locally advanced inoperable stage IIIA/B NSCLC was designed to determine the maximum tolerated paclitaxel dose, to define the safety and toxicity of this combined modality, and to obtain preliminary data on its activity. Patients received a fixed dose of radiotherapy (1.8 Gy/d, 5 days a week, in shrinking-field technique, for a total dose of 59.4 Gy) and concomitant chemotherapy with a 3-hour infusion of paclitaxel once weekly on day 1, initially at a dose of 45 mg/m2, for 3 weeks. This dose remained constant during study levels 1 to 3, with the number of weeks of treatment increasing to 5 and 7 at levels 2 and 3, respectively. At dose level 4, the paclitaxel dose was increased to 55 mg/m2 over 7 weeks. Of 22 NSCLC patients who entered the study, 18 are evaluable for toxicity and response. Responses included one complete and 10 partial remissions; the other seven patients had minimal improvement. The therapy was well tolerated; no severe adverse events were associated with paclitaxel or radiotherapy. This combined modality appears to be a practicable and effective treatment for NSCLC. The maximum tolerated paclitaxel dose has not yet been reached, and dose escalation is planned.
authors.affiliation: Department of Radiation Medicine, Städtische Kliniken Offenbach/Main, Germany.
authors.forename: H G
authors.initials: HG
authors.lastname: Vogt
authors.forename: C
authors.initials: C
authors.lastname: Kolotas
authors.forename: T
authors.initials: T
authors.lastname: Martin
authors.forename: L V
authors.initials: LV
authors.lastname: Schneider
authors.forename: A
authors.initials: A
authors.lastname: Neeb
authors.forename: P S
authors.initials: PS
authors.lastname: Mitrou
authors.forename: K
authors.initials: K
authors.lastname: Diergarten
authors.forename: W
authors.initials: W
authors.lastname: Dornoff
authors.forename: N
authors.initials: N
authors.lastname: Zamboglou
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011879:Radiotherapy Dosage
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel