title: Activity of Pemetrexed on brain metastases from Non-Small Cell Lung Cancer.
abstract: Brain metastases from Non-Small Cell Lung Cancer are usually associated with poor prognosis and up to now chemotherapy has shown a modest activity upon cerebral localizations. We investigated the role of Pemetrexed, a new, well tolerated multi-target antifolate, on brain metastases.
  
  
  METHODS
  We collected 39 patients with evidence of cerebral nervous system (CNS) localizations from Non-Small Cell Lung Cancer (NSCLC) before starting treatment with Pemetrexed as second-line or further-line therapy.
  
  
  RESULTS
  We confirmed the good tolerability of Pemetrexed even in that setting of patients and we reported a progressive disease (PD) in 12 patients (30.8%), a stable disease (SD) and partial response (PR) in 12 (30.8%) and 15 (38.4%) patients respectively, with an overall clinical benefit obtained in 69% of patients. The cerebral response to Pemetrexed was interesting with a cerebral radiological benefit obtained in 32 patients (82%), while 7 patients only showed brain progressive disease. Overall median survival was 10 months. All irradiation-naïve patients and those with clear radiological evidence of cerebral progression after brain radiotherapy and before Pemetrexed, overall 22 patients, were included in one group, in order to avoid overlapping effects between brain radiotherapy and Pemetrexed over CNS localizations. Within that setting, we demonstrated an overall clinical benefit (SD+PR) and cerebral benefit in 63% and 68%, of patients respectively. Distribution of patients by overall response to Pemetrexed and CNS response was highly suggestive of activity of Pemetrexed on brain metastases.
  
  
  CONCLUSIONS
  We demonstrated the good tolerability of Pemetrexed even in patients with advanced NSCLC and brain metastases, and we found a very good overall response rate with evidence of activity on brain localizations.
authors.affiliation: Medical Oncology A, IRCCS-CRO, 33081 Aviano (PN), Italy. abearz@cro.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bearz
authors.forename: Isabella
authors.initials: I
authors.lastname: Garassino
authors.forename: Marcello
authors.initials: M
authors.lastname: Tiseo
authors.forename: Orazio
authors.initials: O
authors.lastname: Caffo
authors.forename: Hector
authors.initials: H
authors.lastname: Soto-Parra
authors.forename: Massimo
authors.initials: M
authors.lastname: Boccalon
authors.forename: Renato
authors.initials: R
authors.lastname: Talamini
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
authors.forename: Marco
authors.initials: M
authors.lastname: Bartolotti
authors.forename: Viviana
authors.initials: V
authors.lastname: Murgia
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Berretta
authors.forename: Umberto
authors.initials: U
authors.lastname: Tirelli
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology / Q000532:radiotherapy / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology / Q000532:radiotherapy / Q000556:secondary*; D018450:Disease Progression; D005260:Female; D005971:Glutamates / Q000008:administration & dosage* / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine