Intraoperative photodynamic therapy after pleuropneumonectomy in patients with malignant pleural mesothelioma - Dose finding and toxicity results

Objective: To determine the optimal administered dose of meta-tetrahydroxyp henylchlorin (mTHPC) for intraoperative photodynamic therapy (IPDT) in rese cted malignant pleural mesothelioma (MPM). The primary objective of this co mbination treatment was to improve local tumor control. Design: Phase I/II close escalation study. Setting: Two Dutch cancer centers. Patients: The study included 28 patients (2 women, 26 men), with pathologic ally confirmed MPM. The mean age was 57 Scars (age range, 37 to 68 years), and the World Health Organization performance score was 0 to 1. Epithelial mesotheliomas were found in 17 patients, a sarcomatous mesothelioma was fou nd in 1 patient, and mixed epithelial sarcomatous mesotheliomas were found in 10 patients. Methods: Patients were injected with 0.075 mg/kg (4 patients), 0.10 mg/kg ( 19 patients), or 0.15 mg/kg (5 patients) mTHPC 4 or 6 days before undergoin g surgery and IPDT. Complete surgical resection (re, pleuropneumonectomy) w as followed by integral illumination with monochromatic light of 652 nm (10 J/cm(2)). The real-time fluence rate measurements were performed using fou r isotropic detectors in the chest cavity to calculate the total light dose . Results: Dose-limiting toxicity was reached at die level of 0.15 mg/kg mTHP C. Three patients died in the perioperative period, and one death was direc tly related to photodynamic therapy. Real-time dosimetry identified 12 pati ents in whom additional illumination had to be given to the diaphragmatic s inuses, which were unavoidably shielded during integral illumination. In tw o patients, illumination was cancelled clue to the insufficient resectabili ty of the tumor. The median survival time for all 28 patients was 10 months . Local tumor control, 9 months after treatment, was achieved in 13 of the 26 patients treated with IPDT. Conclusion: IPDT using mTHPC, combined with a pleuropneumonectomy, resulted in local control of disease in 50% of the treated cases. The considerable toxicity associated with die procedure, however, precludes its recommendati on for widespread use. Stricter patient selection and improvements of the I PDT technique may, reduce the toxicity.