Intrapleural infusion of activated macrophages and gamma-interferon in malignant pleural mesothelioma: a phase II study.
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.
Monnet
Isabelle
I
Department of Pneumology, Center Hospitalier Intercommunal de Créteil, Créteil, France.
Breau
Jean-Luc
JL
Moro
Denis
D
Lena
Hervé
H
Eymard
Jean-Christophe
JC
Ménard
Olivier
O
Vuillez
Jean-Philippe
JP
Chokri
Mohamed
M
Romet-Lemonne
Jean-Loup
JL
Lopez
Manuel
M
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*
D000970:Antineoplastic Agents; D007371:Interferon-gamma