title: A prospective phase II trial of vinblastine and methotrexate in multivessel intraluminal pulmonary vein stenosis in infants and children.
abstract: OBJECTIVE
  To determine the safety and efficacy of the chemotherapeutic agents vinblastine and methotrexate in the treatment of children with progressive multivessel intraluminal pulmonary vein stenosis (PVS).
  
  
  METHODS
  Children received weekly vinblastine and methotrexate for a period of 1 year. Outcomes (for patients receiving ≥1 month of chemotherapy) were classified separately for patients with isolated PVS and PVS with congenital heart disease (CHD). Primary efficacy outcome was "response to treatment" categorized by echocardiographic criteria of response. Survival to 1 year was also evaluated. All adverse events were classified according to Cancer Therapy Evaluation Program, Common Terminology Criteria version 3.0. Events were further classified as related to chemotherapy, cardiac, or other causes.
  
  
  RESULTS
  Among 29 patients enrolled, 28 received at least one dose of chemotherapy and were evaluable for toxicity, while 23 were evaluable for response (21 CHD, 2 isolated). Both patients in the isolated group had progressive disease and died. Overall, 33% (7/21) of patients with PVS and CHD had stable disease; 1-year survival of 38%; and four patients continue in remission (93, 96, 124, and 125 months after treatment initiation). While both cardiac-related (19%) and chemotherapy-related (53%) toxicities were common, most were asymptomatic laboratory changes. Grade 3 (13%) and grade 4 (4%) toxicities were reversible, and no treatment-related grade 5 toxicities were observed.
  
  
  CONCLUSIONS
  We report on the first prospective trial of chemotherapy for infants and children targeting the presence of myofibroblastic cells within the lesions of PVS based on myofibroblastic proliferation associated with desmoid tumors of infancy. The toxicity profile resulted in numerous treatment delays and interruptions that, combined with limited information on the natural history of PVS in this patient population, hampered our ability to determine the true efficacy of this approach. These results will be important as a baseline for clinical trials in this patient population.
authors.affiliation: Department of Cardiology, Children's Hospital, Boston, MA, USA.
authors.forename: Maliha
authors.initials: M
authors.lastname: Rehman
authors.forename: Kathy J
authors.initials: KJ
authors.lastname: Jenkins
authors.forename: Amy L
authors.initials: AL
authors.lastname: Juraszek
authors.forename: Jean A
authors.initials: JA
authors.lastname: Connor
authors.forename: Kimberlee
authors.initials: K
authors.lastname: Gauvreau
authors.forename: Muhammad
authors.initials: M
authors.lastname: Muneeb
authors.forename: Laureen M
authors.initials: LM
authors.lastname: Sena
authors.forename: Steven D
authors.initials: SD
authors.lastname: Colan
authors.forename: Terry
authors.initials: T
authors.lastname: Saia
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kieran
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D058628:Myofibroblasts / Q000187:drug effects / Q000473:pathology; D011446:Prospective Studies; D011667:Pulmonary Veins / Q000187:drug effects* / Q000473:pathology; D011668:Pulmonary Veno-Occlusive Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D013781:Texas; D013997:Time Factors; D016896:Treatment Outcome; D014463:Ultrasonography; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D014747:Vinblastine; D008727:Methotrexate