A REVIEW OF PHYSICAL, CHEMICAL, PHARMACOLOGICAL AND CLINICAL DATA
Photolon® is a agent for PDT ( 1, 3, 5, 8 -
sodium-vapor salt) 0.1 for intravenous injections designed and produced on
pharmaceutical company "Belmedpreparaty" Belarus.
Photosensitizer for photodynamic
therapy and diagnosis
Photolon comprises a
molecular complex of a sodium salt of chlorin e6 and its derivatives
with low-molecular polymer component of intravenous drugs.
Photolon is a dry scentless porous
substance of a dark-green color, soluble in water and salt solutions (25 mg, 50
mg, 100 mg vials)
Mechanism of action
The essential feature of
photodynamic therapy is the presence of a photosensitizer, which upon its
administration into the organism selectively accumulates in a certain type of
tissue, and upon irradiation with light of a certain wavelength, produces
particles toxic to this type of tissue.
The initial stage includes
photoactivation of the photosensitizer by its irradiation by light with a
certain wavelength. This is followed by energy transfer from the excited
photosensitizer molecule to molecular oxygen present in tissues. This process
leads to production of singlet oxygen which interacts with lipids and other
components of cell membranes thus leading to disruption of their integrity and,
as a result, to the cell death. The second possible mechanism of the
photosensitizer effect can be connected with production of free radical
particles. These particles can be created as a result of an interaction of an
excited photosensitizer molecule immediately with molecular components of the
cell, of with an oxygen molecule. The laser treatment induces a photochemical,
not a thermal, effect.
Photolon is a
second-generation photosensitizer showing a high therapeutic activity.
Photolon is characterized by
strong absorption band in the long-wavelength region, which allows using light
from the long-wavelength part of the visible range which penetrates deeper into
biological tissues, and thus provide a possibility of treatment of relatively
massive and deep-lying tumors. Upon intravenous administration, Photolon is
highly tumorotropic, possess a high uptake rate in target tissues, have a low
phototoxicity, and is virtually completely removed from the body during several
Effect of Photolon on the
depth and frequency of the complete tumor necrosis
a) (sarcoma M-1) in the rat
Photolon at the dose of 2.5
mg/kg was accompanied by light irradiation of 100 J/cm2; the depth
of tumor necrosis comprises 11.6±0.5 mm. The frequencies of the complete tumor
necrosis is 100%.
b) alveolar liver cancer RS-1in the
Photolon at the dose of 2.5
mg/kg was accompanied by light irradiation of 50 J/cm2, the depth of
tumor necrosis comprises 12.2±0.7 mm. The complete tumor necrosis is achieved
in 100% of cases.
multicentral phase I and phase II trials of Photolon were carried out at the Medical Radiological Scientific Center (Obninsk, Russia) and Scientific Research Institute
for Oncology and Medical Radiology (Minsk, Belarus). PDT with Photolon (1.5–3.0
mg/kg) was carried out for 82 patients (61 – malignant skin neoplasm, 10 –
malignant lip neoplasm, 5 – breast cancer with skin metastases, and 6 –
malignant melanoma with skin metastases). The complete and partial destruction
of malignant tissue was obtained in 85–95% and 5–15% of cases, respectively.
Additionally, Photolon was applied in treatment of Kaposi’s sarcoma.
The accumulation level of
Photolon in the tumour tissue is 2–20 times higher compared to normal tissue.
The above quantity depends on a number of factors including, but not limited
to, the photosensitizer dose, and tumour growth stage and rate. The accumulation
level of Photolon in tumour tissue increases with the photosensitizer dose
administered. A higher accumulation level of Photolon in tumour was found to be
characteristic of fast-growing tumours. One of the important advantages of
Photolon over other photosensitizers is its fast elimination from the organism: only trace amounts of the preparation are found 24 h
after its intravenous injection.
INDICATIONS TO ADMINISTRATION
Photolon is applied for
photodynamic therapy of basal-cell skin cancer, flat-cell skin cancer,
metatypical skin cancer, flat-cell cancer of the lip, intra- and subcutaneous
metastases of breast cancer, intracutaneous metastases of melanoma, and
Caposi’s sarcoma; photodynamic therapy of mucous membrane cancer (vulva
cancer, uterus cervix cancer, and rectum cancer).
Photosensitizer is applied for
photodynamic diagnosis of neoplasms.
Hypersensitivity to the product,
cardiovascular diseases (decompensated), liver and/or renal insufficiency.
Pregnancy. Nursing mothers.
Not administered in pediatric practice.
Photolon should be administered as a slow
intravenous injection (dropwise) over 30 minutes at 2.5-3 mg/kg body weight.
Reconstitute the adequate dose of Photolon in 200 ml 0.9% Sodium Chloride
Injection, shake well until dissolved. Do not mix Photolon with other drugs in
the same solution.
Initiate 660-670 wavelength
laser light delivery to the patient 3-4 hours following injection of Photolon.
A total light dose of 100 - 600 J/cm2 during one or two sessions of
laser treatment of one or several areas is administered, depending on the
clinical form and morphology of the malignant neoplasm, and on the infiltration
Concominant use of local anesthetics is not
Clinical experience has identified no
interactions resulting from topical or systemic administration of other drugs
(including analgesic drugs) concomitantly with Photolon.
Antioxidants, Bien, Reparef-2 Ointment
could facilitate early epithelization of tissue damage, enhance connective
tissue growth, reduce pain.
Most toxicities are associated with local
effects in the region of illumination. Fever and pain in the region of lazer
illumination may occur. In patients with cardiovascular diseases sometimes
Systemically induced effects associated with
photodynamic therapy with Photolon is mild photosensitivity. Photosensitivity
reactions as a rule are associated with disturbance of precausions to avoid
sunlight and bright indoor light (mild hyperemia, edema without pigmentation).
POSSIBLE COMPLICATIONS AND PRECAUTIONS
patients who receive Photolon must observe precautions to avoid exposure of
skin and eyes to direct sunlight or bright indoor light. Photolon should be
administered in darkened room.
should not be used during pregnancy.
It is not
known whether this drug is excreted in human milk. Because many drugs are
excreted in human milk and because potential for serious adverse reactions in
nursing infants from Photolon, women receiving Photolon must not breast feed.
and effectiveness in children have not been established.
Use in elderly patient
There was no apparent difference
in effectiveness or safety in patients over 60 years of age compared to younger
people. Dose modification based upon age is not required.
Sunscreen creams should be administered
following administration of Photolon.
There is no information on overdosage
situation involving Photolon.
LD50 of Photolon is not less than 140 mg/kg
in the rat.
In animals toxic effects include dyspnoea,
tachycardia, hypertension, excitation, following central nervous system
Photolon for ingection is supplied as a freeze-dried cake
or powder as 25 mg, 50 mg, and 100 mg vials.
Store at temperature not more + 10°C, in
dark (protected from light) place.