Adjuvant intraoperative photodynamic therapy diminishes the rate of local recurrence in a rat mammary tumour model.

The use of photodynamic therapy (PDT) as an adjunct to curative tumour resection was investigated in a tumour recurrence model, using rat mammary adenocarcinoma BN472. Tumours were inoculated subcutaneously in 60 animals and resected after 21 days of growth. Immediately after removal, the operation site was exposed to 320-450 nm light of 0.1 W cm-2 and 60 J cm-2 after photosensitisation with either Photofrin (5 mg kg-1 i.v. 48 h before illumination) or 5-aminolaevulinic acid (ALA) (2 mg ml-1 in drinking water for 9 days). Porphyrin concentrations were measured in tissue samples. After 28 days, animals treated with adjunctive PDT had a significantly longer tumour-free interval than controls (P < 0.01); median 25 days (Photofrin), 18 days (ALA), 14 days (controls). Moreover, in the PDT groups significantly fewer rats had lymph node metastasis. A prophyrin concentration ratio between tumour and mammary tissue of 2:1 was found after Photofrin and 4:1 after ALA. The results indicate that adjuvant intraoperative PDT may be a safe and effective method of destroying residual tumour, thereby preventing locoregional tumour recurrence.

[1]  Ann Smith.  Mechanisms of Toxicity of Photoactivated Artificial Porphyrins Role of Porphyrin‐Protein Interactions , 1987, Annals of the New York Academy of Sciences.

[2]  J. H. Wilson,et al.  Acute intermittent porphyria in The Netherlands. Heterogeneity of the enzyme porphobilinogen deaminase. , 1986, The Netherlands journal of medicine.

[3]  P. Zondervan,et al.  Light-dark-shift stress, with special reference to spontaneous tumor incidence in female BN rats. , 1986, Journal of the National Cancer Institute.

[4]  J C Kennedy,et al.  NON‐INVASIVE TECHNIQUE FOR OBTAINING FLUORESCENCE EXCITATION AND EMISSION SPECTRA IN VIVO , 1986, Photochemistry and photobiology.

[5]  T J Dougherty,et al.  DISTRIBUTION AND ELIMINATION OF PHOTOFRIN II IN MICE , 1989, Photochemistry and photobiology.

[6]  T J Dougherty,et al.  Intraoperative photodynamic therapy for retroperitoneal sarcomas , 1988, Cancer.

[7]  Z. Malik,et al.  Destruction of erythroleukaemic cells by photoactivation of endogenous porphyrins. , 1987, British Journal of Cancer.

[8]  R. Straight,et al.  Intraoperative phototherapy (PDT) and surgical resection in a mouse neuroblastoma model , 1990, Lasers in surgery and medicine.

[9]  A. Andrén-sandberg,et al.  Recurrence of exocrine pancreatic cancer--local or hepatic? , 1993, Hepato-gastroenterology.

[10]  T J Dougherty,et al.  Photodynamic therapy in patients with colorectal cancer , 1986, Cancer.

[11]  A. Purushotham,et al.  Breast‐conserving surgery and tumour bed positivity in patients with breast cancer , 1994, The British journal of surgery.

[12]  J. Marescaux,et al.  Experimental photodynamic therapy with a copper metal vapor laser in colorectal cancer , 1992, International journal of cancer.

[13]  Toshiya Takeda,et al.  An evaluation of radical resection for pancreatic cancer based on the mode of recurrence as determined by autopsy and diagnostic imaging , 1993, Cancer.

[14]  N. Schoenfeld,et al.  The heme biosynthetic pathway in lymphocytes of patients with malignant lymphoproliferative disorders. , 1988, Cancer letters.

[15]  M. Buyse,et al.  Adjuvant therapy of colorectal cancer. Why we still don't know. , 1988, JAMA.

[16]  Z. Hall.  Cancer , 1906, The Hospital.

[17]  C J Gomer,et al.  Photodynamic therapy in the treatment of malignancies. , 1989, Seminars in hematology.

[18]  J Moan,et al.  PHOTOBLEACHING OF PORPHYRINS USED IN PHOTODYNAMIC THERAPY AND IMPLICATIONS FOR THERAPY , 1987, Photochemistry and photobiology.

[19]  C. Rimington,et al.  The biochemical approach to cancer therapy: a short essay. , 1993, The International journal of biochemistry.

[20]  F. Ames,et al.  Management of local and regional recurrence after mastectomy or breast-conserving treatment. , 1990, The Surgical clinics of North America.

[21]  A. J. MacRobert,et al.  Oral versus intravenous administration of 5-aminolaevulinic acid for photodynamic therapy. , 1993, British Journal of Cancer.

[22]  G. Voortman,et al.  Porphyrin synthesis by human hepatocytes and HepG2 cells--effects of enzyme inducers and delta-aminolevulinic acid. , 1991, Toxicology.

[23]  L. L. Needham,et al.  Simultaneous quantification of erythrocyte zinc protoporphyrin and protoporphyrin IX by liquid chromatography. , 1986, Clinical chemistry.

[24]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[25]  W. Star,et al.  WAVELENGTH DEPENDENCE OF HEMATOPORPHYRIN DERIVATIVE PHOTODYNAMIC TREATMENT EFFECTS ON RAT EARS , 1990, Photochemistry and photobiology.

[26]  A E Profio,et al.  SKIN PHOTOSENSITIVITY: DURATION and INTENSITY FOLLOWING INTRAVENOUS HEMATOPORPHYRIN DERIVATES, HpD and DHE , 1987, Photochemistry and photobiology.

[27]  J C Kennedy,et al.  Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. , 1992, Journal of photochemistry and photobiology. B, Biology.

[28]  R. van Hillegersberg,et al.  Selective accumulation of endogenously produced porphyrins in a liver metastasis model in rats. , 1992, Gastroenterology.

[29]  T. Dougherty.  Photodynamic therapy. , 1993, Photochemistry and photobiology.

[30]  S. Steinberg,et al.  Phase I study of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors. , 1993, International journal of radiation oncology, biology, physics.

[31]  B W Henderson,et al.  Hyperthermic potentiation of photodynamic therapy employing photofrin I and II: Comparison of results using three animal tumor models , 1987, Lasers in surgery and medicine.