Primary Outcome Measures
- Number of Patients having the full multimodal treatment without unacceptable and unexpected toxicities (grade ≥ 3) graded According to NCI CTC Version 4.0 [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures
- Number of responders or stable patients after surgery [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]
- Progression-free survival (PFS) [ Time Frame: through study completion, an average of 13 months ] [ Designated as safety issue: Yes ]
- Quality of life assessed by a specific questionnaire MPM (HCCA EORTC-30) [ Time Frame: Baseline and at 12 months ] [ Designated as safety issue: Yes ]
Detailed Description
- 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
Eligibility
- 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.
