title: Phase I trial of outpatient weekly docetaxel, carboplatin and concurrent thoracic radiation therapy for stage III unresectable non-small-cell lung cancer: a Vanderbilt cancer center affiliate network (VCCAN) trial.
abstract: OBJECTIVE
  Docetaxel, an active agent for non-small cell lung cancer (NSCLC), has demonstrated activity as a radiosensitizer in numerous pre-clinical studies. We conducted a phase I trial to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of weekly Docetaxel, Carboplatin with concurrent thoracic radiation therapy (TRT) in patients with unresectable stage III NSCLC.
  
  
  METHODS
  In this phase I clinical trial, Docetaxel was administered weekly as a 1-h intravenous infusion for 6 weeks with a starting dose of 20 mg/m(2). Docetaxel doses were escalated by 10 mg/m(2) increments in successive cohorts of three patients. DLT was defined as grade >or=3 nonhematologic and hematologic toxicity according to RTOG toxicity criteria. Once the DLT of Docetaxel alone was reached, weekly Carboplatin (AUC 2) was added at a DLT-2 dose of Docetaxel (two dose levels below that of dose limiting toxicity). Docetaxel doses were again escalated at 10 mg/m(2) increments in successive cohorts of three new patients to define further DLT and MTD of Docetaxel/Carboplatin with TRT. TRT was administered to the primary tumor and regional lymph nodes (40 Gy) followed by a boost to the tumor (20 Gy).
  
  
  RESULTS
  Fifteen patients were entered onto this study with Docetaxel alone through three dose escalations (from 20 to 40 mg/m(2) weekly). The DLT of weekly Docetaxel/TRT was esophagitis and the MTD was 30 mg/m(2) per week for 6 weeks. Nine more patients were added with the Docetaxel/Carboplatin/TRT regimen. The DLT of weekly Docetaxel/Carboplatin with TRT was esophagitis and the MTD of Docetaxel was 20 mg/m(2) per week with weekly Carboplatin (AUC 2). There were 2 complete responses and 13 partial responses in 25 evaluable patients (RR 60%).
  
  
  CONCLUSIONS
  This combination regimen has activity with manageable toxicity in patients with stage III NSCLC. A phase II study is planned to define activity.
authors.affiliation: Vanderbilt University Medical School, Nashville, TN, USA. hak.choy@mcmail.vanderbilt.edu
authors.forename: H
authors.initials: H
authors.lastname: Choy
authors.forename: R F
authors.initials: RF
authors.lastname: DeVore
authors.forename: K R
authors.initials: KR
authors.lastname: Hande
authors.forename: L L
authors.initials: LL
authors.lastname: Porter
authors.forename: P A
authors.initials: PA
authors.lastname: Rosenblatt
authors.forename: B
authors.initials: B
authors.lastname: Slovis
authors.forename: K
authors.initials: K
authors.lastname: Laporte
authors.forename: Y
authors.initials: Y
authors.lastname: Shyr
authors.forename: D H
authors.initials: DH
authors.lastname: Johnson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D043823:Taxoids; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin; D017239:Paclitaxel