title: Phase I study of pemetrexed and cisplatin with concurrent high-dose thoracic radiation after induction chemotherapy in patients with unresectable locally advanced non-small cell lung cancer.
abstract: OBJECTIVE
  This is a phase I, escalating-dose trial targeting exclusively patients with non-small cell lung cancer (NSCLC), investigating pemetrexed and fixed-dose cisplatin concurrently administered with high-dose radiotherapy (RT) after induction chemotherapy (CT). Primary objective was to determine the maximum tolerated dose and recommended phase II dose of pemetrexed.
  
  
  METHODS
  Patients with unresected stage III NSCLC, planned V20 ≤ 35%, and FEV ≥ 1.3 L, were treated every 21 days for 2 cycles (pemetrexed 500 mg/m2; cisplatin 75 mg/m2), followed by 2 cycles of concurrent CT-RT: pemetrexed starting dose was 400 mg/m2, escalated up to 800 mg/m2 per 100mg/m2 dose level (DL), cisplatin at 75 mg/m2 and RT at fixed dose of 66 Gy/33 fractions.
  
  
  RESULTS
  Nine of 10 enrolled patients (age range 46-68 years; 6 men; ECOG PS 0 [6 patients], PS 1 [4]; stage IIIA [1], IIIB [9]; 6 adenocarcinomas, 3 squamous cell carcinomas, 1 large cell carcinoma) were entered on 3 DLs. Dose escalation of pemetrexed was conducted up to 600 mg/m2 based on the independent safety monitoring board recommendation. One dose-limiting toxicity occurred at DL3: Grade 4 septic shock. Grade 3 related toxicities: 2 neutropenia at DL3, 2 lymphopenia per DL (3 recurrent), 2 leukopenia (1 recurrent) at DL3, 1 gastric pain (DL3), 1 nausea and 1 recurrent vomiting (DL2). No Grade 3/4 radiation-related toxicities were observed. No toxic death was observed. Disease control rate was 77.7% (1 CR, 4 PR, 2 SD). One-year survival rate was 90%.
  
  
  CONCLUSIONS
  This phase I report of pemetrexed is dedicated to NSCLC with induction therapy and fixed high-dose RT. Pemetrexed at 500 mg/m2, concurrently given with cisplatin and RT was well tolerated and appears to be the only third-generation agent that can likely be recommended safely at full dose in future trials with concurrent RT.
authors: Department of Radiation Oncology, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France. francoise.mornex@chu-lyon.fr
authors: Françoise
authors: F
authors: Mornex
authors: Karine
authors: K
authors: Peignaux
authors: Thierry
authors: T
authors: Germain
authors: Virginie
authors: V
authors: Wautot
authors: Nadia
authors: N
authors: Chouaki
authors: Nawel
authors: N
authors: Bourayou
authors: Jean-Marc
authors: JM
authors: Tourani
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D060828:Induction Chemotherapy; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D008231:Lymphopenia / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000209:etiology; D000068437:Pemetrexed; D011879:Radiotherapy Dosage; D016896:Treatment Outcome; D014839:Vomiting / Q000209:etiology
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D002945:Cisplatin