Objective: To determine the optimal administered
dose of meta-tetrahydroxyphenylchlorin (mTHPC) for intraoperative
photodynamic therapy (IPDT) in resected malignant pleural mesothelioma
(MPM). The primary objective of this combination treatment was to
improve local tumor control.
Design: Phase I/II dose
Setting: Two Dutch cancer
Patients: The study included 28 patients (2
women, 26 men), with pathologically confirmed MPM. The mean age was 57
years (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 found in 1 patient, and
mixed epithelial sarcomatous mesotheliomas were found in 10
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 undergoing surgery and IPDT.
Complete surgical resection (ie, pleuropneumonectomy)
was followed by integral illumination with monochromatic light of 652
nm (10 J/cm2). The real-time fluence rate measurements were
performed using four isotropic detectors in the chest cavity to
calculate the total light dose.
toxicity was reached at the level of 0.15 mg/kg mTHPC. Three patients
died in the perioperative period, and one death was directly related to
photodynamic therapy. Real-time dosimetry identified 12 patients
in whom additional illumination had to be given to the diaphragmatic
sinuses, which were unavoidably shielded during integral illumination.
In two patients, illumination was cancelled due to the insufficient
resectability 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 the
procedure, however, precludes its recommendation for widespread use.
Stricter patient selection and improvements of the IPDT
technique may reduce the toxicity.