title: Escalating paclitaxel doses combined with carboplatin/etoposide and thoracic radiotherapy as preoperative or definitive treatment for stage III non-small cell lung cancer.
abstract: We have evaluated escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with carboplatin, cisplatin, etoposide, and concurrent thoracic radiotherapy in patients with stage III non-small cell lung cancer. Dose-limiting toxicity was observed at paclitaxel 90 mg/m2. Subsequent modifications resulted in a new regimen, which consists of a 3-hour paclitaxel infusion on day 1 (three dose levels: 80, 100, and 120 mg/m2), etoposide 40 mg/m2 intravenously over 1 hour daily on days 2 to 5, and carboplatin given at an area under the concentration-time curve of 4 mg/mL x min on day 1 after paclitaxel. Treatment courses were repeated every 28 days. Eleven patients considered eligible for surgery received two courses. Nonsurgical patients (five) received three courses. No episodes of grade > or = 3 nausea and vomiting, dermatitis, anorexia, esophagitis, or thrombocytopenia were observed. The dose-limiting toxicity (grade 4 granulocytopenia) occurred in three of five patients at 120 mg/m2 paclitaxel (level 3). Grade 3 radiation pneumonitis was observed in three patients. Nine patients have undergone pulmonary resection: four pneumonectomies, four lobectomies, and one segmental resection. No operative deaths, respiratory insufficiency, or cardiovascular complications were observed. Clinical partial remissions have been observed in 11 of 16 patients overall, and two histologic complete remissions were achieved in nine surgical patients. Our preliminary results show that pulmonary resection is feasible following treatment with radiation and concurrent paclitaxel-containing chemotherapy. Although the maximum tolerated paclitaxel dose in the present study was relatively low, favorable initial responses warrant further study of paclitaxel-containing combination chemotherapy and concurrent radiation. We next plan to delete etoposide from our chemoradiotherapy regimen and escalate the paclitaxel dose.
authors.affiliation: Department of Radiation Therapy, Rush University Medical Center, Chicago, IL, USA.
authors.forename: P
authors.initials: P
authors.lastname: Bonomi
authors.forename: S
authors.initials: S
authors.lastname: Siddiqui
authors.forename: S
authors.initials: S
authors.lastname: Lincoln
authors.forename: M
authors.initials: M
authors.lastname: Sharma
authors.forename: D
authors.initials: D
authors.lastname: Recine
authors.forename: W
authors.initials: W
authors.lastname: Warren
authors.forename: L P
authors.initials: LP
authors.lastname: Faber
mesh_terms: D000380:Agranulocytosis / Q000139:chemically induced; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage* / Q000633:toxicity; D011014:Pneumonia / Q000139:chemically induced; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel