Photosensitizer Radachlorin®: Skin cancer PDT phase II clinical trials☆
Introduction
This paper represents the full report of a phase IIb clinical trials for the photosensitizer Radachlorin [1] in Russia (August 2003–August 2005), previously published partly [2], [3], [4], [5], set forth in 2 different clinical trial Protocols (3 hospitals for “Radachlorin”®, i.v. administration (RCS); 2 hospitals for “Radachlorin”®, topical administration, RCG), aimed at obtaining confirmation of previous data [6], [7], [8] on applicability, safety and tolerability of Radachlorin-LAKHTA-MILON photodynamic therapy, as well as optimizing PDT regimes for improving photodynamic tumor destruction examining various drug doses, and light exposures. This followed laboratory studies (1999–2001) and clinical phase 0 and I trials (conducted in Russia in 3 hospitals in July 2001–March 2003, involving 67 patients with i.v. and 35 patients with topical administration of photosensitizer), for cutaneous basal cell carcinoma (BCC) treatment protocols.
Section snippets
Photosensitizer
“Radachlorin”® active pharmaceutical ingredient (API) as well as its finished formulation “Radachlorin”® gel for topical application 0.1% 25 g (RCG) were produced in a GMP-certified facility of RADA-PHARMA Co. Ltd. (Moscow, Russia).
“Radachlorin”® active pharmaceutical ingredient (API) is represented by the total sodium salts of chlorins (6.50/7.50 g), and purified water (up to 100.00 mL).
RCG is “Radachlorin”® (1.43 g) (total sodium salts of chlorins—0.10 g), purified water (up to 100.00 mL), and
Results
Safety study showed no side effects and a good tolerability of RCS by patients, save for moderate pain, depending on individual sensitivity, tumor localization and irradiation field. There was no normal skin/subdermal tissue damage after both laser and sunlight exposure. The main part (98%) of the drug was excreted or metabolized in the first 48 h.
A low dark toxicity, 48 h clearance of RCS from the human's body and a low affinity to the skin helped to avoid the skin photosensitivity to daylight
Discussion
“Radachlorin”® active substance is chemically stable in solutions for 1.5 years at 0 + 8 °C in the dark. When introduced to embryocarcinoma T36 bearing mice, it had maximal tumor uptake within 0.5–5 h post-injection with tumour-to-skin ratio around 14 by 3 h post-injection and clearance period about 24 h. In the animal PDT experiments “Radachlorin”®, active substance showed an expressed specific PDT activity, causing an intensive but bearable by animals necrotic action to the tumors [10], [11], [12],
Acknowledgments
The authors are highly grateful to the supervisors of the clinical trials V.A. Privalov (Prof., M.D., D.Med.Sc.), V.V. Sokolov (Prof., M.D., D.Med.Sc.), A.V. Geinits (Prof., M.D., D.Med.Sc.), as well as to physicists making fluorescent diagnosis possible: A.V.Lappa (Prof., D.Med.Sc.), M.V.Evnevich (Ph.D.), N.N.Boulgakova (Ph.D.).
This work would certainly have been impossible without I.D. Zalevskiy (Ph.D.) and S.E.Goncharov, who provided the lasers.
We would also like to thank the staff member of
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This paper was supported by the Natural Health Foundation (Noordwijkerhout, The Netherlands, www.naturalhealthfoundation.com).
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