Intrapleural Photodynamic Therapy in a Multimodal Treatment for Patients With Malignant Pleural Mesothelioma

phase II trial assessing the feasibility of an experimental multimodal treatment combining:

• surgery of the MPM: extended pleurectomy/decortication (eP/D)
• intra-operative (intrapleural) photodynamic therapy (PDT). Briefly, each patient will receive porfimer sodium (PHOTOFRIN®) (2 mg/kg) 24 hours before eP/D (IV injection on 3-5 minutes). Cutaneous light precautions will be instituted immediately and for the next 4 weeks.

then:

• prophylactic chest radiotherapy of surgical scars to prevent tumor seeding (3 x 7 Gray)
• adjuvant standard chemotherapy by (cis)platin 75 mg/m2 and pemetrexed 500 mg/m2 up to 6 cycles (1 cycle every 3 weeks), with oral folic acid (400 μg daily) and vitamin B12 (1000 μg Q9W) supplementation
• follow-up

Inclusion criteria

• histologically-proved epithelioid malignant pleural mesothelioma (MPM) on biopsies obtained before eP/D surgery
• tumor stage: no tumor extension to controlateral lung, mediastinum, peritoneum or myocardium (<T4); mediastinal lymph nodes extension: cN2 but no bulky N2 or N3), no metastasis (M0)
• Performance status WHO PS 0-1
• patients fit to have surgery (eP/D) and chemotherapy (cisplatin-pemetrexed), based on clinical examination, complete normal biological work-up, full assessment by cardiac and pulmonary function tests. Predicted post-surgical values should be sufficient for normal daily life: FEV1>40%; pre-surgical DLCO>50% predicted value and VO2max >15 ml/min/kg; (left ventricular) cardiac function >50% and no significant pulmonary artery hypertension
• written informed consent must be obtained before inclusion and randomization

Exclusion criteria

• Another histologic subtype than epithelioid MPM at the time of diagnosis
• Bulky N2, N3 and/or M1 stage (UICC/IMIG 1995)
• prior chemotherapy for mesothelioma
• prior radiotherapy of thorax, neck or upper abdomen
• other malignancy treated within 5 years, except basal cell carcinoma or in situ carcinoma of the cervix
• contra-indication for MPM surgery or chemotherapy (cisplatin and pemetrexed): cardiac failure, pulmonary hypertension, liver or kidney dysfunction (GFR<60 ml/min), uncontrolled infection, previous major neurotoxicity or ototoxicity,... or other severe condition according to the investigator
• pregnancy or breast feeding
• contra-indication for porfimer sodium (Photofrin): porphyria or known hypersensitivity to porphyrins, severe hepatic impairment, tracheo-oesophageal or broncho-oesophageal fistula, suspected erosion of major blood vessels due to risk of massive, potentially fatal haemorrhage
• A previous talc pleurodesis during diagnostic thoracoscopy is NOT an exclusion criteria but talc on mediastinal pleura should be avoided to not keep away from eP/D.