title: Intrapleural infusion of activated macrophages and gamma-interferon in malignant pleural mesothelioma: a phase II study.
abstract: OBJECTIVE
  Intrapleural immunotherapy has shown some activity in patients with malignant mesothelioma. We conducted a multicentric pilot phase II study to evaluate the tolerance and the activity of intrapleurally infused autologous human activated macrophages (AM Phi) in patients with stage IA, IB, and IIA malignant pleural mesothelioma (MPM).
  
  
  METHODS
  AM Phi derived from in vitro monocyte culture were infused into the pleura of patients every week for 8 consecutive weeks. Each infusion was followed 3 days later by an intrapleural injection of 9 millions units of gamma-interferon (gamma-IFN) in an attempt to prolong the in vivo activation of infused AM Phi. Response was assessed by CT scan and thoracoscopy when possible. If the patient's disease progressed after AM Phi treatment, an additional treatment was left to the choice of the investigator.
  
  
  METHODS
  Nineteen patients with histologically proven stage IA, IB, or IIA MPM were enrolled. Two patients were excluded before any AM Phi infusion because of complications impeding infusion. Seventeen patients were actually treated. After completion of the AM Phi cellular therapy, 10 patients were treated with chemotherapy as their diseases progressed.
  
  
  RESULTS
  The overall response rate of patients actually treated was 14%. When including the two patients enrolled but not treated, the overall response "in intention to treat" was 11%; two patients had a partial response, with a duration of response of 30 months and 3 months, respectively. One patient, who could not be evaluated by thoracoscopy because of pleural symphysis, is still alive without any clinical or radiologic sign of disease 69 months after treatment. No major adverse effects were observed during the infusion of either AM Phi or gamma-IFN, and there was no interruption of treatment because of toxicity. However, symphysis was observed in 7 of 14 patients who received the complete treatment. The median survival of patients actually treated, including those who received chemotherapy after AM Phi, was 29.2 months.
  
  
  CONCLUSIONS
  Combined infusion of AM Phi and gamma-IFN was well tolerated in patients with MPM; however, it had limited antitumor activity.
authors.affiliation: Department of Pneumology, Center Hospitalier Intercommunal de Créteil, Créteil, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Monnet
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Breau
authors.forename: Denis
authors.initials: D
authors.lastname: Moro
authors.forename: Hervé
authors.initials: H
authors.lastname: Lena
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Eymard
authors.forename: Olivier
authors.initials: O
authors.lastname: Ménard
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Vuillez
authors.forename: Mohamed
authors.initials: M
authors.lastname: Chokri
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Romet-Lemonne
authors.forename: Manuel
authors.initials: M
authors.lastname: Lopez
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007263:Infusions, Parenteral; D007371:Interferon-gamma / Q000008:administration & dosage*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008654:Mesothelioma / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D010994:Pleura; D010997:Pleural Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D007371:Interferon-gamma