title: A phase I study of pemetrexed, carboplatin, and concurrent radiotherapy in patients with locally advanced or metastatic non-small cell lung or esophageal cancer.
abstract: OBJECTIVE
  The primary objective of this phase I study was to determine the maximum tolerated dose for pemetrexed, alone and in combination with carboplatin, with concurrent radiotherapy.
  
  
  METHODS
  Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) or esophageal cancer were treated every 21 days for two cycles. Regimen 1 was pemetrexed (200-600 mg/m(2)); regimen 2 was pemetrexed (500 mg/m(2)) with escalating carboplatin doses (AUC = 4-6). Both regimens included concurrent radiation (40-66 Gy; palliative-intent doses were lower).
  
  
  RESULTS
  Thirty patients (18 locally advanced and 12 metastatic with dominant local symptoms) were enrolled, with an Eastern Cooperative Oncology Group performance status of 0/1/2 (n = 8/21/1). All dose levels were tolerable for regimen 1 (n = 18: 15 NSCLC and 3 esophageal cancers) and regimen 2 (n = 12: all NSCLC). In regimen 1, one dose-limiting toxicity (grade 4 esophagitis/anorexia) occurred (500 mg/m(2)). Grade 3 neutropenia (3 of 18 patients) was the main hematologic toxicity. In regimen 2, one dose-limiting toxicity (grade 3 esophagitis) occurred (500 mg/m(2); AUC = 6); grade 3/4 leukopenia (4 of 12 patients) was the main hematologic toxicity. Four complete responses (2 pathology proven) and eight partial responses were observed. When systemically active chemotherapy doses were reached, further dose escalation was discontinued, and a phase II dose-range was established (pemetrexed 500 mg/m(2) and carboplatin AUC = 5-6).
  
  
  CONCLUSIONS
  The combination of pemetrexed (500 mg/m(2)) and carboplatin (AUC = 5 or 6) with concurrent radiation is well tolerated, allows for the administration of systemically active chemotherapy doses, and shows signs of activity. To further determine efficacy, safety profile, and optimal dosing, the Cancer and Leukemia Group B study 30407 is currently evaluating this regimen in patients with unresectable stage III NSCLC.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
authors.forename: Tanguy Y
authors.initials: TY
authors.lastname: Seiwert
authors.forename: Philip P
authors.initials: PP
authors.lastname: Connell
authors.forename: Ann M
authors.initials: AM
authors.lastname: Mauer
authors.forename: Philip C
authors.initials: PC
authors.lastname: Hoffman
authors.forename: Christopher M
authors.initials: CM
authors.lastname: George
authors.forename: Livia
authors.initials: L
authors.lastname: Szeto
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Posther
authors.forename: Binh
authors.initials: B
authors.lastname: Nguyen
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Haraf
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy*; D015331:Cohort Studies; D003131:Combined Modality Therapy / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D005260:Female; D005971:Glutamates / Q000008:administration & dosage*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000068437:Pemetrexed
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D016190:Carboplatin