Radiotherapy is commmonly used in the treatment of cancer. It is the primary curative modality in about 30% of patients, and more than half of all cancer patients recieve radiation therapy sometime during the course of their disease. Similar to surgery, radiation therapy is a local-regional modality. When successful, this treatment cures, (by eradicating tumor in the primary side), the draining regional lymphatics, and lymph nodes. Reproductive death – the consequence of DNA damage – is the primary mechanism of tumor destruction. The total dose delivered to the tumor currently is limited by the tolerance of the surrounding normal tissue, e.g. the skin.
Combined modality therapy for cancer is the sequential or simultaneous use of several treatment options, including surgery, radiotherapy, and chemotherapy. It is logistically complex, often associated with serious side-effects, and, generally, restricted to the curative-intent setting. The principle is to acknowledge the limitations inherent in each of the single modalities and to increase as part of a comprehensive treatment plan. Patients with locally or regionally advanced tumors that cannot be readily cured with surgery or radiotherapy benefit from combined modality therapy.
The starting point for judgments concerning the acceptability of normal tissue damage form cancer treatment, e.g. skin damage by radiotherapy alone or by combined modality therapy should always be a realistic expectation of the beneficial effects of that treatment. Clearly, patients and doctors are prepared to accept a high level of toxicity where cure is a reasonable objective. Palliation, on the other hand, requires non-toxic treatments, almost by definition. At the present time surgeons, radiotherapists, and chemotherapists also administer therapies which fall between these extremes. That is, they are neither curative or are they merely palliative. The middle group may be called retardive and applies to those therapies which, as well as relieving or preventing symptoms, show or temporarily reverse the progression of the disease, thus offering a prolongation of survival but not amounting to cure, in the vast majority of patients. For this group in particular, judgments about the acceptability of undesired effects become more difficult as they become more important. This is especially so since the same treatment may be used in all three settings. The problem is compounded by wide differences between patients in what they will accept and also by often undeclared discrepancies between doctor and patient.
A wide variety of skin reactions might occur with radiotherapy alone or with combined modality therapy. Radiation dermatitis, or reactivation of a radiation dermatitis in a previously irradiated field is sometimes seen. In addition, alopecia, pigment changes, cutaneous ulcers, morbilliform eruptions, scleroderma-like reactions with infiltrated plaques have all been reported. The principle risk in this situation is infection which can rapidly lead to massive tissue breakdown, because the immunocompetence of the skin is also heavily impaired.
It would be most helpful for oncologists and patients to have reliable quantitative data on normal tissue damage and prevention and treatment options, if transdermal radiation therapy is considered as a treatment options alone or in combination with other therapeutical modalities; unwanted side-effects should be encountered at the very begining of the treatment planing and coped with the most advanced remedies available.
PraevoSkin ® and Radiotherapy
As PraevoSkin ® has been tested rigorously in clinical studies, one particular promising preventive and therapeutic option has becomes noted. The rationale for developing PraevoSkin ® is as follows:
Radiation therapy, alone or in combination with chemotherapy, mostly works by cancer cell DNA-damage generated by oxygen-derived radicals; reactive oxygen species (ROS) are generated by radiation as well as by chemotherapeutic agents. However, this active principle, is unselective, hits normal and tumor tissue, might cause mutagenesis, carcinogenesis and early aging of the irradiated skin during transdermal radiotherapy a harmful side-effect, which is further increased, if ROS-inducing chemotherapeutical compounds are included into the treatment protocol.
Therefore, it was mandatory to search for treatment options, as already mentioned, which allow during transdermal radiotherapy/chemotherapy, to hit and destroy tumor cells, e.g. in the breast, but minimize the oxidative stress of the skin. During transdermal radiotherapy, and intravenously chemotherapy, the skin is under continuously attack from molecules known as ROS, generated by the high energy radiation beam and/or chemotherapeutic agents. The damages caused by them at the skin are kown as oxidative stress.
Over the past decade, the potential of the pineal hormone melatonin as a therapeutic agent in a variety of diseases has been recognized. Melatonin has effects in sleep disorders, it is used as an immunoregulatory agent with clinical results obtained in cancer immunotherapy, Melatonin exerts important effects on hematopoietic cells by stimulating the production of novel T helper cell opioid cytokines. The most intriguing discover, however, was the free radical (ROS) scavenger activity, neutralizing a number of free radicals and reactive oxygen and nitrogen species. Melatonin stimulates several antioxidative enzymes which increase its efficiency as an antioxidant. Melatonin is the most powerful natural antioxidant known in nature. Melatonin interacts with ROS at a rate constant at least two log-scales more powerful than Vitamin E.
With PraevoSkin ® it was possible for the first time to design a new dermato-cosmetics, containing melatonin in relevant amounts and in a lipid-encaged form, and, therefore, exhibiting its potent antioxidative activity at the surface of the skin, when applied topically before and during the course of radiation. The therapeutic dosis applied to the tumor target volume is not impaired, but the surface of the skin is protected from harmful side-effects caused by ROS.
PraevoSkin ® helps to prevent skin damage during radiation treatment and combined modalities, which are based on the principle to generate ROS for DNA-damage and cell killing.
A double blinded, randomised and prospective 6-weeks clinical trial, using the criteria of the American Society of Radiology to rate harmful side effects of radiation treatment, has shown that PraevoSkin ® application before, during and after treatment:
A long-term study (6 months) is under the way and results will be reported shortly; a preliminary analysis reveals that the results obtained in the the 6-weeks study (Figure 1) can be confirmed.
Editor’s Notes
We thank Professor Zaeker from the University of Witten in Germany very much for his first submission to the IAS Anti-Aging Bulletin.
His work in helping to protect the skin from the harmful effects of radiation (used in cancer therapy) is very important indeed, and it clearly highlights the ability of PraveoSkin ® to be efficacous. What’s more, the unique ingredients in this new product range have also been shown in one study to reduce wrinkles in skin by as much as 43.9% in only 1-month, (we hope to report more about that on our website soon).
It would therefore appear that not only is PraevoSkin ® an excellent topical cream for radiation therapy, but that it will also assist in general skin aging as a preventative to skin damage. Furthermore, it would appear that due to its properties, PraevoSkin ® is a superb after-sun cream, and would make an ideal protective against photoaging, especially when combined with Professor Ionescu’s Solaris ® sun-cream, details of which are also available in this Bulletin.
PraveoSkin ® can currently be found on the IAS order form listed as Melatonin Topical.
