title: Multicenter phase II trial of Motexafin gadolinium and pemetrexed for second-line treatment in patients with non-small cell lung cancer.
abstract: BACKGROUND
  Motexafin gadolinium (MGd) disrupts redox-dependent pathways by inhibiting oxidative stress-related proteins leading to apoptosis. MGd selectively targets tumor cells, disrupting energy metabolism and repair mechanisms, rendering cells more prone to apoptosis. Preclinical studies with MGd and pemetrexed show significant tumor growth delay in lung cancer cell lines.
  
  
  METHODS
  Patients with non-small cell lung cancer, Eastern Cooperative Oncology Group performance status 0 to 1, who had received one previous platinum containing regimen and normal organ function were treated with MGd 15 mg/kg and pemetrexed 500 mg/m q21days. Patients were allowed to receive more than one regimen if the initial treatment was in the adjuvant or curative setting and administered >12 months earlier. The primary end point was to demonstrate a 40% rate of 6-month progression free survival (PFS).
  
  
  RESULTS
  Seventy-two patients (30 women, 42 men), performance status 0/1 (30/42), and a median age of 63 years were enrolled. Most patients (96%) were current or former smokers. All histologic types were represented (squamous/adenocarcinoma/other: 28%, 42%, 31%). Number of prior regimens: 1: 69%; 2: 26%, and >2: 4%. Median number of cycles administered was (range) 2 (1-12).
  
  
  RESULTS
  grade 3/4 neutropenia was noted in 8.3% with febrile neutropenia in 1.4%, thrombocytopenia in 8.3%, fatigue in 9.7%, and pneumonia in 11.1%. There were no complete responses, 8.1% had partial response, 56.5% had stable disease, and 35.5% had progressive disease as their best response. Twenty-three percent of patients were progression free at 6 months and the median PFS was 2.6 months with an overall survival of 8.1 months.
  
  
  CONCLUSIONS
  The combination of MGd and pemetrexed was well tolerated with toxicity similar to that of pemetrexed alone. However, the study did not achieve its end point of 40% 6-month PFS. The response rate, PFS, and overall survival did not seem markedly different than prior phase II and phase III studies of pemetrexed alone. Consequently, there are no further plans for development of this combination.
authors.affiliation: University of Maryland Greenebaum Cancer Center, Baltimore, MD 21201, USA. medelman@umm.edu
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Edelman
authors.forename: Gregory
authors.initials: G
authors.lastname: Otterson
authors.forename: Joseph
authors.initials: J
authors.lastname: Leach
authors.forename: Thomas
authors.initials: T
authors.lastname: Malpass
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
authors.forename: Dennie
authors.initials: D
authors.lastname: Jones
authors.forename: Tarak D
authors.initials: TD
authors.lastname: Mody
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Govindan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008665:Metalloporphyrins / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D010865:Pilot Projects; D011379:Prognosis; D016879:Salvage Therapy; D015996:Survival Rate
chemical_list: D005971:Glutamates; D008665:Metalloporphyrins; D000068437:Pemetrexed; D006147:Guanine; C437683:motexafin gadolinium