Photodynamic therapy with chlorins for diffuse malignant mesothelioma: initial clinical results

Our plain-English summary of Photodynamic therapy with chlorins for diffuse malignant mesothelioma: initial clinical results, by H.B. Ris, H.J. Altermatt, R. Inderbitzi, et al (British Journal of Cancer, 1991).

The study

• Authors: H.B. Ris, H.J. Altermatt, R. Inderbitzi, R. Hess, B. Nachbur, J.C. Stewart, Q. Wang, C.K. Lim, R. Bonnett, M.C. Berenbaum
• Journal: British Journal of Cancer
• Published: 1991;64(6):1116-20
• Cited by: 173 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Four patients underwent intraoperative photodynamic therapy after surgery with meso-tetra-(hydroxyphenyl)-chlorin (mTHPC-PDT) for diffuse malignant mesothelioma. Preliminary procedures were performed in two patients in order to establish the efficacy of mTHPC-PDT and to optimise its tumoricidal effect. The tumoricidal effect was related to the mTHPC dose, light dose and the time interval between sensitation and activation. 0.3 mg kg-1 mTHPC activated after 48 h with 10 Joules cm-2 of non-thermal laser light at 650 nm resulted in a 10 mm deep tumour infarction, due to tumour vessel necrosis and thrombosis. The mTHPC tissue concentration was up to 14 times higher in the tumour than in normal tissues. Skin photosensitivity was mild, dose dependent and occurred 3 to 10 days after administration of mTHPC. According to the results obtained, intraoperative mTHPC-PDT was performed following pleuropneumonectomy in two, pleurectomy and lobectomy in one and pleurectomy in one patient. Ten Joules cm-2 were delivered to the diaphragm and the costophrenic sulcus and 5 Joules cm-2 to the remaining thoracic cavity. The postoperative course was marked by loss of appetite, fluid retention, hypoproteinemia and severe chest pain. One patient succumbed from aspiration pneumonia. The remaining patients developed no neural or vascular alterations and no bronchial stump insufficiency during follow-up. mTHPC-PDT following surgical tumour resection deserves further evaluation in good risk patients with diffuse malignant mesothelioma.

In plain English

This pilot study from the University of Bern, Switzerland, tested photodynamic therapy (PDT) in four men aged 46 to 65 with diffuse malignant mesothelioma affecting one side of the chest. PDT uses a light-activated drug, here one called mTHPC. All four men had possible occupation-related exposure to asbestos. In two patients, the authors first tried different drug doses, light doses and waiting times on small tumour areas. With 0.3 mg/kg of mTHPC and laser light given 48 hours later at 10 Joules per square centimetre, biopsies showed tumour death about 10 mm deep, with no viable tumour cells at the edges. Drug levels were up to 14 times higher in tumour than in skin and other normal tissues. Skin sensitivity to sunlight was mild. All four patients then had surgery followed by PDT of the chest cavity. Afterwards they had loss of appetite, fluid retention, low blood protein and severe chest pain. One patient died of aspiration pneumonia on the sixth day after surgery. At three months, one survivor showed disease on the other side of the chest. The authors concluded that the approach deserves further evaluation in good-risk patients.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: pilot clinical study (case series of four patients): preliminary dose-finding PDT in two patients, then surgery followed by intraoperative PDT in all four
• Who was studied: Four men aged 46, 48, 65 and 50 with diffuse malignant mesothelioma, treated at the University of Bern, Switzerland. Disease was on the right side in patients 1, 2 and 4 and on the left in patient 3. Tumour types were epithelial, biphasic, sarcomatous and mixed. The article gives no study dates.
• Exposure: The study examined a treatment, not an exposure. All four patients had possible occupation-related asbestos exposure; no fiber types, products, jobs or doses are given. The treatment was mTHPC (meso-tetra-(hydroxyphenyl)-chlorin) activated by 650 nm laser light. The final protocol was 0.3 mg/kg given 48 hours before light: 10 J/cm2 to the diaphragm and costophrenic sulcus and 5 J/cm2 to the rest of the cavity.
• Main results:
  • Preliminary PDT (patients 1 and 2): 0.075 mg/kg mTHPC with 10 J/cm2 of light after 24 hours caused necrosis of approximately 50% of tumour in treated areas.
  • Preliminary PDT: 0.15 mg/kg mTHPC with 10 J/cm2 of light after 24 hours caused 50% to 80% tumour destruction.
  • Preliminary PDT: 0.3 mg/kg with 10 J/cm2 of light after 24 hours caused 10 mm deep complete necrosis in the centre of treated areas, but cells were preserved at the periphery. When the same light dose was given after 48 hours, no viable tumour cells were seen at the periphery.
  • Light doses higher than 10 J/cm2, up to 40 J/cm2, did not produce deeper tumour destruction.
  • The mTHPC concentration was up to 14 times higher in tumour than in skin and other normal tissues.
  • The only side effect seen after mTHPC administration in the preliminary procedures was mild, dose-dependent skin photosensitivity. It appeared 3 to 10 days after the drug was given and lasted 2 to 3 days.
  • After surgery plus PDT, all patients had loss of appetite, fluid retention (up to 8 kg), hypoproteinemia, and more severe chest pain than expected from surgery alone.
  • Patient 3 died of a massive aspiration-induced pneumonia of the other lung on the sixth postoperative day. Patients 1, 2 and 4 were discharged after 3 weeks.
  • Autopsy of patient 3 showed PDT-induced necrosis of the remaining tumour. Underlying structures such as the aorta, nerve ganglion cells and the oesophagus were spared. However, rib cartilage and bone cells and smooth muscle cells of the aorta next to the destroyed tumour were altered.
  • At follow-up, the three surviving patients had no bronchial stump insufficiency and no vascular alterations. Patient 2 had diffuse weakness of the right arm without evidence of a peripheral nerve lesion.
  • About 3 months after the operation, CT scans showed no evidence of disease in patients 2 and 4. Patient 1 showed disease on the other side of the chest and anterior chest wall invasion at a previous biopsy site.
  • PDT added about 2 hours to surgery in patients 1, 2 and 3. A new high-power laser cut the treatment time to 50 minutes in patient 4.
• The authors' conclusion: The authors concluded that mTHPC-PDT showed some reasonable degree of treatment selectivity under clinical conditions, and that mTHPC-PDT following surgical tumour resection deserves further evaluation in good-risk patients with diffuse malignant mesothelioma.
• Limitations the authors state:
  • The optimal combination of drug dose, light dose and time interval had yet to be defined.
  • The large-surface treatment caused a substantial additional burden to patients after surgery.
  • The autopsy findings raised concern about how far normal tissue can be spared when tumour invades it, and late effects on underlying structures need attention.
  • It was difficult to deliver equal and sufficient light to the anterior chest wall, and to the collapsed lung in patient 3.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Necrosis, Diaphragm.

Related studies

• Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts — H.B. Ris, T. Krueger, et al. (1999)
• Experimental assessment of photodynamic therapy with chlorins for malignant mesothelioma — H.B. Ris, A. Giger, et al. (1997)
• Determination of 5,10,15,20-tetra-(m-hydroxyphenyl)chlorin in human plasma by high performance liquid chromatography — Q. Wang, H.B. Ris, et al. (1993)
• Foscan uptake and tissue distribution in relation to photodynamic efficacy — P. Cramers, M. Ruevekamp, et al. (2003)
• Photodynamic therapy as adjuvant therapy in surgically treated pleural malignancies — P. Baas, L. Murrer, et al. (1997)
• Photodynamic therapy for mesothelioma — S.M. Hahn, R.P. Smith, et al. (2001)

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