Bremachlorin® is a light-sensitive compound or photosensitizer that is undergoing careful scientific evaluation and holds promise for optimizing photodynamic therapy (PDT) for cancer. Bremachlorin® is also known as Radachlorin® in Russia, where the agent is clinically approved for various skin and cancer treatments. Preclinical studies are now under way in the Netherlands with a goal toward achieving clinical acceptance in the European Union.

Photosensitizers vary in the ways they are metabolized by the body. The ideal photosensitizing agent is taken up easily by cancer cells and retained within the tumor while being excreted fairly quickly by normal tissues. When the concentration of the agent is much higher in malignant than in normal tissues, this can result in the highly targeted destruction of the tumor, with virtually no side effects.

It has been proposed that Bremachlorin’s high level of therapeutic efficacy as a component of PDT for cancer is related to the ability to readily penetrate biological membranes (thus entering living cells with ease) as well as to a greatly increased accumulation in tumor tissues compared to surrounding healthy tissues.

 

Three Key Components

In addition, Bremachlorin contains three components (Chlorin e6, Chlorin p6, Purpurin 5) that target different aspects of cancer biology:

  • Vascular damage, or interfering with the growth of new blood vessels that in turn enable tumors to grow
  • Damage to the cancer cell’s membranes and cell signaling system, along with increased recognition by the body’s anti-cancer immune defenses
  • Damage to the cancer cell’s internal structures, in particular the mitochondria and DNA.

Thus, the three components in Bremachlorin® result in a unique, multi-faceted tumor-killing potential. The third component, Purpurin 5, is the most critical in terms of finally killing the tumor. Because this compound shows a high degree of chemical instability, it must be combined with the two chlorin compounds in order to become stable and successfully delivered to the tumor.

This trio of compounds explains Bremachlorin’s success as both a therapeutic and a diagnostic agent. When used in fluorescent diagnosis, this trio cause the entire tumor to glow or fluoresce. First the entire tumor fluoresces, then individual cells, and then the organelles.

 

The Leiden-Erasmus Studies

Researchers from two academic centers in The Netherlands—Leiden University Medical Center in Leiden, and Erasmus University Medical Center in Rotterdam—recently demonstrated that Bremachlorin displayed a more lasting tumor-killing potential compared to Chlorin e6 alone. Bremachlorin’s ability to accumulate preferentially in tumors may allow for selective targeting of those tumors.

The Leiden-Erasmus researchers propose that such research can be used to help define an optimal treatment protocol for Bremachlorin-PDT. These research findings were reported in the January 2014 Journal of Biomedical Optics and also in the March 2014 issue of Lasers in Surgery and Medicine.

Cancers of the skin, bladder, brain, breast and lung are just a few of the cancers being considered for future studies of Bremachlorin-PDT. “What we’ve seen in our studies of breast cancer, for example, is that Bremachlorin is taken up very actively by the breast cancer cells, and is retained in the tumor for much longer time periods when compared to other photosenstiizers,” says Clemens Lowik, PhD, one of the Leiden investigators. “Since it’s taken up by the cells and stays much longer than the usual six or seven hours, you are more likely to see better tumor killing. This suggests great potential for breast cancer treatment.”

 

An Overview of Bremachlorin-PDT’s Clinical Potential

PDT has proven ability to destroy tumors as well as infectious bacteria, fungi and viruses. At this time, various Bremachlorin doses and light exposures are being explored in order to determine the optimal protocols for Bremachlorin-PDT as primary and adjuvant treatments for malignant disease. As a primary treatment, this approach has been especially effective in the elimination of small tumors—and in particular, more superficial tumors or those readily exposed to laser or other light sources.

Following the light treatment, the following therapeutic effects have been attributed to Bremachlorin-PDT:

  • greatly obstructed blood flow to the tumor
  • accelerated destruction of the tumor (necrosis)
  • increased activation of anti-cancer immune mechanisms

When used as an adjuvant treatment, Bremachlorin-PDT could be useful in the following situations:

  • to eliminate residual tumor following surgical debulking (i.e., surgical removal of the bulk of the tumor)
  • to help prevent the formation of metastases following surgery
  • to lower the dose of radiotherapy needed for treating larger, inoperable tumors
  • to eliminate cancer cells that have become resistant to chemotherapy and radiation treatments. It may be used to.

PDT can be used before, during or after surgery. Chemotherapeutic and radiation treatments can enhance the effect of PDT with Bremachlorin ®. When combined with these treatments, however, the Bremachlorin infusion must precede chemotherapy and follow radiation treatment.

 

Side effects, Contraindications and Precautions

Following intravenous administration of Bremachlorin®, there is a risk of skin hypersensitivity to therapeutic doses of irradiation during and after light treatment (photosensitivity). Symptoms of skin photosensitivity may include the skin becoming red, irritated, swollen, and sore, sometimes with small blisters. Such reactions are typically only seen with extended exposure to sunlight following PDT.

Once the Bremachlorin preparation is administered, the patient must avoid prolonged exposure (longer than 30 minutes) to direct sunlight. In the summertime, such avoidance should be practiced for two consecutive days after the treatment; in wintertime, avoidance should be practiced for 24 hours after the treatment. Bremachlorin is contraindicated for anyone with a known hypersensitivity to any ingredient of the drug.

No test of the preparation has been conducted with pregnant women. Therefore, as with other medicinal preparations, Bremachlorin should not be administered during pregnancy. The most “high risk” period may be during the first three months of gestation unless the physician is convinced that the expected benefit for the mother’s health will be greater than a potential risk to the fetus.

For more information, please see Appendix A of our ebook series, Photomedicine Discoveries.