Journ.al of Photochemistry

and Photobiology, B: Biology, 6 (1990)

443-449

443

News and Views

Proposal of a protocol brain tumours C. PERRIA, Clinica

for the photodynamic

therapy of malignant

G. CASU and E. SGARAMELLA

Neurochinwgica,

Universitb di Sassari,

07100 Sassari

(Italy)

1. Introduction

A variety of protocols are currently used for the photodynamic therapy (PDT) of malignant brain tumours (MBTs) [l-8]. In spite of technical difficulties, such studies have succeeded in demonstrating that PDT can be employed to treat MBTs. However, the differences in the clinical procedures generate some uncertainties and confusion among clinicians. There is an urgent need for a standard protocol which gives a reliable basis for evaluating the efficiency of the phototherapeutic treatment as compared with other treatment modalities. We propose a PDT protocol for MBTs and hope to stimulate useful discussions on this very important problem. The main features of the protocol are described in the following sections. 2. Criteria fw admission of the patients to the protocol Several workers have used PDT to treat patients who have developed recurrences of MBTs after surgery and/or radiotherapy and chemotherapy [l-3, 5, 81. In these cases, PDT was applied during surgical resection of the recurrence, in some instances by stereotactic interstitial implantation of optical fibres into the tumour [ 31. Some patients were in a hopeless condition. Other neurosurgeons have performed PDT on untreated tumours [ 1, 2, 41, and have also treated the patients by radiotherapy. In these cases, the actual effectiveness of PDT may be masked by the possible synergism with radiotherapy. The effectiveness of PDT and patient survival are affected by the location and size of the tumour, since these factors may prevent or facilitate uniform irradiation of the tumour bed. The importance of radical resection of MBTs has been shown in ref. 9 and by McCulloch et al. [4] who removed two glioblastomas and exposed the patients to PDT and radiotherapy; both patients survived for 6 years. We suggest that any patient, of any age, suffering from an MBT should be admitted to the protocol, provided that the tumour has not been previously treated and radical resection and satisfactory decompression are possible. This criterion excludes malignant tumours of the skull base and benign tumours. Radical resection denotes the removal of all the tumour which the surgeon can detect and remove. Only cerebral computerized tomography or magnetic resonance 8-10 days later can confirm the radical resection; otherwise the patients must be excluded from the protocol. loll-1344/90/$3.50

0 Elsevier

Sequoia/Printed in The Netherlands

444

NEWSANDVEWS

3. Evaluutim of neurological jindings and quality of life a$er PDT The criterion often adopted, i.e. “survival of patients”, is very uncertain, especially if used to assess the effectiveness of PDT; survival may depend on reanimation and antioedema therapies and may be prolonged under conditions which can be defined “survival” but are certainly not “life”. It is essential to determine to what extent the neurological findings and quality of life of the patients are improved by PDT. To this aim Karnofsky grading [9] should be used. 4. Choice of the photosensitizing agent Haematoporphyrin derivative (HpD) is the most frequently used photosensitizer [l-5], although haematoporphyrin (Hp) is also used [8]. Drug dosage ranges between 2.5 and 5 mg kg-’ body weight. The presence of the drug in the tumour, which can be detected by its red-orange fluorescence, is not sufficient to explain why PDT is successful or fails. The drug concentration needs to be accurately measured and this can be done only after extraction from the tissue and spectrophotofluorometric analysis. In this context, Hp is preferable since it has a more homogeneous composition than HpD, and its concentration can be expressed in terms of micrograms of drug per gram of tumour. Hp is also more suitable for clearance studies in plasma, urine and faeces. The serum content of Hp decreases at a faster rate than that of HpD, which may decrease general skin photosensitivity [8]. The tumours should be exposed to light at 12-24 h after injection of Hp at a dose of 5 mg kg-‘. 5. Choice of irradiation parameters Initial attempts to employ PDT for MBTs involved the use of 620-640 nm light from low power He-Ne lasers [2], filtered quartz halogen lamps [ 1, 4, 81 or dye lasers [3-81. More recently, gold vapour lasers have been employed [4]. Usually, the light is focused onto the surface of the tumour bed, while depth effects are obtained by insertion of optical fibres into the tumour [3]. In some cases the light power has been too weak to induce an efficient photoactivation of the drug, whereas in others it has been too strong and has led to the generation of hyperthermia. It is often difficult to express the delivered light dose precisely, especially when fibres are inserted. Present experience suggests that the most appropriate PDT treatment, following radical excision of the tumour, is irradiation with 600-640 nm light using a power in the range 300-400 J cm-‘. At least 300 J cm-’ should be delivered. In our opinion, the in-depth activation of the photoprocess using a large number of optical fibres is not feasible due to the excessive length of the operation time. The best results of PDT for MBTs seem to be obtained by a combination of surgery, PDT and radiotherapy [ 3, 41. Thus MBTs should also receive adequate radiotherapy doses (not less than 50-60 Gy). The efficacy of PDT should then be assessed by comparing patients treated by surgery and radiotherapy with patients treated by surgery, PDT and radiotherapy.

NEWSANDVIEWS

445

6. Post-operative evaluation of patients Computerized tomography and magnetic resonance scans should be carried out at 7, 30, 90, 180 and 365 days after PDT. Any recurrence must be measured antero-posteriorly and latero-laterally; the data must be correlated with the neurological check-up and Karnofsky grading. If decompressive craniectomy has been performed during or after operation, it would be useful to describe the possible swelling of the flap. 1 I. J. Forbes, P. A. Cowled, A. S. Y. Leong, A. D. Ward, R. B. Black, A. G. Black and F. J. Jacka, Phototherapy of human tumours using hematoporphyrin derivative, Med. J. Amt., 2 (1980) 489-493. 2 C. Perria, T. Capuzzo, G. Cavagnaro, R. Datti, N. Francavigha, C. Rivano and V. E. Tercero, First attempts at the photodynamic treatment of human ghomas, J. Neurosurg. Sci., 244 (1980) 119-129. 3 E. R. Laws, D. A. Cortese, J. H. Kinsey, R. T. Eagan and R. E. Anderson, Photodynamic therapy in the treatment of malignant brain tumours; a phase I (feasibility) study, Ne-urosurger?/, 9 (1981) 672-678. 4 G. A. J. McCuIIoch, I. J. Forbes, K. Lee See, P. A. Cowled, F. J. Jacka and A. D. Ward, Phototherapy in malignant brain tumours, in D. R. Doiron and C. J. Gomer (eds.), Porphyrin Localization and Treatment of Tuwwum, Alan R. Liss, New York, 1984, pp. 709-717. 5 P. J. MuIIer and B. C. Wilson, Photodynamic therapy: cavitary illumination of malignant cerebral tumours using a laser-coupled inflatable balloon, Can. J. NeuroZ. Sci., 12 (1985) 371-373. 6 A. H. Kaye, G. Morstyn and D. Brownbill, Adjuvant high-dose photoradiation therapy in the treatment of cerebral glioma: a phase l-2 study, J. Neurosurg., 67 (1987) 500-505. 7 H. Kostron, G. Weiser, E. Fritsch and V. Grunert, Photodynamic therapy of mahgnant brain tumours: clinicaI and neuropathological results, Photo&em. Photobiol., 46 (1987) 937-943. 8 C. Perria, M. Carrai, A. FaIzoi, G. Orunesu, A. Rocca, G. Massarehi, N. Francavigha and G. Jori, Photodynamic therapy of mahgnant brain tumours: clinical results of, di6icuIties with, questions about, and future prospects for the neurosurgical applications, Neurosurgery, 23 (1988) 557-563. 9 D. A. Kamofsky and J. H. Burchenal, The clinical evaluation of chemotherapeutic agents in cancer, in C. M. McLeod (ed.), Evaluation of Chemotherapeutic Agents, Columbia University Press, New York, 1949, pp. 191-205.

Topical application

of liposomes

DANIEL B. YAROSH Applied

Genetics

Inc., 205 Baalo

Ave., Freeport,

NY 11520 (U.S.A.)

Introduction Liposomes are microscopic vesicles formed by amphipathic liquid membranes. They are used as models for biological membranes and have recently been exploited as delivery vehicles for systemic administration of drugs. Of particular interest to the photobiologist is their topical use. They are included in cosmetics and yet discounted as therapeutically ineffective when applied to the skin surface. In fact, liposomes are applied topically for different purposes and their effectiveness depends on their penetration and mechanism of drug delivery. 1.

Proposal of a protocol for the photodynamic therapy of malignant brain tumours.

Journ.al of Photochemistry and Photobiology, B: Biology, 6 (1990) 443-449 443 News and Views Proposal of a protocol brain tumours C. PERRIA, Clin...
245KB Sizes 0 Downloads 0 Views