title: A phase II trial of second-line pemetrexed in adults with advanced/metastatic osteosarcoma.
abstract: BACKGROUND
  Osteosarcoma is the most common primary malignant tumour in young adults. An effective treatment strategy for relapsed patients is still not defined. Pemetrexed is a multitargeted antifolate with a mode of action similar to, and a range of action broader than that of methotrexate. The primary objective of this phase II study was to determine tumour response rate in patients with high-grade, advanced/metastatic osteosarcoma. Secondary end-points included progression-free survival (PFS), overall survival (OS) and safety.
  
  
  METHODS
  Pemetrexed 500mg/m(2) was administered on day 1 of 21-day cycles with folic acid and vitamin B(12) supplementation. At least 5 tumour responses in a targeted population of 32 were required to consider further investigation.
  
  
  RESULTS
  Thirty-two patients (median age, 43.3 years; range, 18.6-76.0) with 1 prior chemotherapy regimen for high-grade advanced/metastatic osteosarcoma were enrolled. Thirty (93.8%) patients had an ECOG performance status ≤ 1 and 29 (90.6%) had metastases in the lung. One patient had partial response (3.1%) and 5 (15.6%) had stable disease. Median PFS and OS were 1.4 months (95% CI: 1.4-1.7) and 5.5 months (95% CI: 2.3-10.5), respectively. The most common drug-related grade 3/4 toxicities were leukopaenia, asthaenia and elevated alanine aminotransferase in 3 (9.4%) patients each. One patient died due to multi-organ failure considered possibly related to the study drug.
  
  
  CONCLUSIONS
  Pemetrexed 500mg/m(2) administered on day 1 of 21-day cycles as second-line treatment to patients with advanced/metastatic high-grade osteosarcoma was generally well tolerated but did not meet minimal response expectations for further investigation in this patient population.
authors.affiliation: Marseille and Aix-Marseille University, Marseille, France. florence.duffaud@ap-hm.fr
authors.forename: Florence
authors.initials: F
authors.lastname: Duffaud
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Egerer
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.forename: Hisham
authors.initials: H
authors.lastname: Rassam
authors.forename: Ulrike
authors.initials: U
authors.lastname: Boecker
authors.forename: B
authors.initials: B
authors.lastname: Bui-Nguyen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D000068437:Pemetrexed; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine