Annals of Surgical Oncology

, Volume 12, Issue 10, pp 808–816 | Cite as

Photodynamic Therapy With 5,10,15,20-Tetrakis(m-Hydroxyphenyl) Bacteriochlorin for Colorectal Liver Metastases Is Safe and Feasible: Results From a Phase I Study

  • Frederieke H. van Duijnhoven
  • Jeroen P. Rovers
  • Kerstin Engelmann
  • Zdenko Krajina
  • Shaun F. Purkiss
  • Frans A. N. Zoetmulder
  • Thomas J. Vogl
  • Onno T. Terpstra



The prognosis for patients with liver metastases from colorectal carcinoma is limited because of the low number of patients who are eligible for curative hepatic resection. In this phase I study, 31 liver metastases in 24 patients with nonresectable metastases from colorectal carcinoma were treated with photodynamic therapy (PDT).


The photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)bacteriochlorin (mTHPBC) was intravenously administered in a dose of .6 mg/kg (n = 12) or .3 mg/kg (n = 12). After 120 hours (n = 18) or 48 hours (n = 6), tumors were illuminated for 300 to 600 seconds through percutaneously inserted optical fibers with a light dose of 60 J/cm of diffuser (740 nm).


Tumor necrosis at 1 month after PDT was achieved in all treated lesions. Laser treatment was associated with mild pain (n = 8) and transient subclinical hepatotoxicity (n = 21). In one patient, PDT damage to the pancreas was inflicted, and in another patient, PDT damage of the skin occurred, but no serious clinical complications from PDT were reported. Administration of .6 mg/kg of mTHPBC led to transient phlebitis in 10 patients, and 3 patients experienced mild skin phototoxicity after excess light exposure.


Colorectal liver metastases that are ineligible for resection can be safely and effectively treated with interstitial mTHPBC-based PDT.


Photodynamic therapy Liver metastases Colorectal cancer Phase I. 


  1. 1.
    Boyle RW, Dolphin D. Structure and biodistribution relationships of photodynamic sensitizers. Photochem Photobiol 1996;64:469–85PubMedGoogle Scholar
  2. 2.
    Bugelski PJ, Porter CW, Dougherty TJ. Autoradiographic distribution of hematoporphyrin derivative in normal and tumor tissue of the mouse. Cancer Res 1981;41:4606–12PubMedGoogle Scholar
  3. 3.
    Fingar VH. Vascular effects of photodynamic therapy. J Clin Laser Med Surg 1996;14:323–8PubMedGoogle Scholar
  4. 4.
    Korbelik M. Induction of tumor immunity by photodynamic therapy. J Clin Laser Med Surg 1996;14:329–34PubMedGoogle Scholar
  5. 5.
    Dougherty TJ, Cooper MT, Mang TS. Cutaneous phototoxic occurrences in patients receiving Photofrin. Lasers Surg Med 1990;10:485–8PubMedGoogle Scholar
  6. 6.
    Ackroyd R, Kelty CJ, Brown NJ, Stephenson TJ, Stoddard CJ, Reed MW. Eradication of dysplastic Barrett’s oesophagus using photodynamic therapy: long-term follow-up. Endoscopy 2003;35:496–501CrossRefPubMedGoogle Scholar
  7. 7.
    Moghissi K, Dixon K, Thorpe JA, Stringer M, Moore PJ. The role of photodynamic therapy (PDT) in inoperable oesophageal cancer. Eur J Cardiothorac Surg 2000;17:95–100CrossRefPubMedGoogle Scholar
  8. 8.
    Ortner M. Photodynamic therapy for cholangiocarcinoma. J Hepatobiliary Pancreat Surg 2001;8:137–9CrossRefPubMedGoogle Scholar
  9. 9.
    Waidelich R, Stepp H, Baumgartner R, Weninger E, Hofstetter A, Kriegmair M. Clinical experience with 5-aminolevulinic acid and photodynamic therapy for refractory superficial bladder cancer. J Urol 2001;165:1904–7CrossRefPubMedGoogle Scholar
  10. 10.
    van Hillegersberg R, Marijnissen JP, Kort WJ, Zondervan PE, Terpstra OT, Star WM. Interstitial photodynamic therapy in a rat liver metastasis model. Br J Cancer 1992;66:1005–14PubMedGoogle Scholar
  11. 11.
    Purkiss SF, Dean R, Allardice JT, Grahn MF, Williams NS. An interstitial light delivery system for photodynamic therapy within the liver. Lasers Med Sci 1993;8:253–7Google Scholar
  12. 12.
    Purkiss SF, Grahn MF, Abulafi AM, Dean R, Allardice JT, Williams NS. Multiple fiber interstitial photodynamic therapy of patients with colorectal liver metastases. Lasers Med Sci 1994;9:27–35Google Scholar
  13. 13.
    Hara N, Ichinose Y, Motohiro A, Ohta M, Yagawa K. Distribution of hematoporphyrin derivative in normal and malignant tissue. Jpn J Exp Med 1988;58:139–43PubMedGoogle Scholar
  14. 14.
    Copper MP, Tan IB, Oppelaar H, Ruevekamp MC, Stewart FA. Meta-tetra(hydroxyphenyl)chlorin photodynamic therapy in early-stage squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 2003;129:709–11CrossRefPubMedGoogle Scholar
  15. 15.
    Rovers JP, de Jode ML, Grahn MF. Significantly increased lesion size by using the near-infrared photosensitizer 5,10,15,20-tetrakis (m-hydroxyphenyl)bacteriochlorin in interstitial photodynamic therapy of normal rat liver tissue. Lasers Surg Med 2000;27:235–40CrossRefPubMedGoogle Scholar
  16. 16.
    Yow CM, Chen JY, Mak NK, Cheung NH, Leung AW. Cellular uptake, subcellular localization and photodamaging effect of temoporfin (mTHPC) in nasopharyngeal carcinoma cells: comparison with hematoporphyrin derivative. Cancer Lett 2000;157:123–31CrossRefPubMedGoogle Scholar
  17. 17.
    Rovers JP, Saarnak AE, Molina A, Schuitmaker JJ, Sterenborg HJ, Terpstra OT. Effective treatment of liver metastases with photodynamic therapy, using the second-generation photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC), in a rat model. Br J Cancer 1999;81:600–8CrossRefPubMedGoogle Scholar
  18. 18.
    Rovers JP, de Jode ML, Rezzoug H, Grahn MF. In vivo photodynamic characteristics of the near-infrared photosensitizer 5,10,15,20-tetrakis(M-hydroxyphenyl) bacteriochlorin. Photochem Photobiol 2000;72:358–64CrossRefPubMedGoogle Scholar
  19. 19.
    Rovers JP, Saarnak AE, de Jode M, Sterenborg HJ, Terpstra OT, Grahn MF. Biodistribution and bioactivity of tetra-pegylated meta-tetra(hydroxyphenyl)chlorin compared to native meta-tetra(hydroxyphenyl)chlorin in a rat liver tumor model. Photochem Photobiol 2000;71:211–7CrossRefPubMedGoogle Scholar
  20. 20.
    Green S, Weiss GR. Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria. Invest New Drugs 1992;10:239–53PubMedGoogle Scholar
  21. 21.
    Goldberg SN, Charboneau JW, Dodd GD III, et al. Image-guided tumor ablation: proposal for standardization of terms and reporting criteria. Radiology 2003;228:335–45Google Scholar
  22. 22.
    Green S, Weiss GR. Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria. Invest New Drugs 1992;10:239–53PubMedGoogle Scholar
  23. 23.
    Wagnieres G, Hadjur C, Grosjean P, et al. Clinical evaluation of the cutaneous phototoxicity of 5,10,15,20-tetra(m-hydroxyphenyl)chlorin. Photochem Photobiol 1998;68:382–7CrossRefPubMedGoogle Scholar
  24. 24.
    Lustig RA, Vogl TJ, Fromm D, et al. A multicenter phase I safety study of intratumoral photoactivation of talaporfin sodium in patients with refractory solid tumors. Cancer 2003;98:1767–71CrossRefPubMedGoogle Scholar
  25. 25.
    Chen J, Keltner L, Christophersen J, et al. New technology for deep light distribution in tissue for phototherapy. Cancer J 2002;8:154–63PubMedGoogle Scholar
  26. 26.
    Parikh AA, Curley SA, Fornage BD, Ellis LM. Radiofrequency ablation of hepatic metastases. Semin Oncol 2002;29:168–82CrossRefPubMedGoogle Scholar
  27. 27.
    Curley SA. Radiofrequency ablation of malignant liver tumors. Ann Surg Oncol 2003;10:338–47Google Scholar
  28. 28.
    Solbiati L, Goldberg SN, Ierace T, et al. Hepatic metastases: percutaneous radio-frequency ablation with cooled-tip electrodes. Radiology 1997;205:367–73Google Scholar
  29. 29.
    Mack MG, Straub R, Eichler K, et al. Percutaneous MR imaging-guided laser-induced thermotherapy of hepatic metastases. Abdom Imaging 2001;26:369–74CrossRefPubMedGoogle Scholar
  30. 30.
    Vogl TJ, Mack MG, Straub R, Roggan A, Felix R. Magnetic resonance imaging–guided abdominal interventional radiology: laser-induced thermotherapy of liver metastases. Endoscopy 1997;29:577–83PubMedGoogle Scholar
  31. 31.
    Lu DS, Raman SS, Vodopich DJ, Wang M, Sayre J, Lassman C. Effect of vessel size on creation of hepatic radiofrequency lesions in pigs: assessment of the “heat sink” effect. AJR Am J Roentgenol 2002;178:47–51PubMedGoogle Scholar

Copyright information

© The Society of Surgical Oncology, Inc. 2005

Authors and Affiliations

  • Frederieke H. van Duijnhoven
    • 1
  • Jeroen P. Rovers
    • 1
  • Kerstin Engelmann
    • 2
  • Zdenko Krajina
    • 3
  • Shaun F. Purkiss
    • 4
  • Frans A. N. Zoetmulder
    • 5
  • Thomas J. Vogl
    • 2
  • Onno T. Terpstra
    • 1
  1. 1.Department of Surgery, K6-RLeiden University Medical CenterLeidenThe Netherlands
  2. 2.Diagnostische und Interventionelle RadiologieZentrum der Radiologie, Johann Wolfgang Goethe-UniversitätFrankfurt am MainGermany
  3. 3.Department for Oncology and RadiotherapyClinical Hospital OsijekOsijek
  4. 4.Department of SurgeryThe Royal London HospitalLondonUnited Kingdom
  5. 5.Department of Medical OncologyThe Netherlands Cancer Institute/Slotervaart HospitalAmsterdamThe Netherlands

Personalised recommendations