Abstract
Curaderm BEC5 is a topical cream formulation that contains chemotherapeutic agents solasodine rhamnosyl glycosides (SRGs) and is very effective for treating nonmelanoma skin cancers with excellent cosmetic end results. This report gives a brief overview of Curaderm BEC5.
NonMelanoma Skin Cancer Incidence and available treatments
Skin cancer incidence is increasing at alarming rates. In the US alone, more than two million people develop over 3.5 million nonmelanoma skin cancers every year. This translates to more than 300 percent increase in cancer incidence since 1992 [1, 2]. This observation does not only apply to the US, but is a worldwide phenomenon. Skin cancer incidence is considered by some as an epidemic and its incidence is higher than all other cancers combined.
A variety of treatments are available for nonmelanoma skin cancers with good outcomes, especially if the cancers are detected and treated in the early stages of development. However, there are some serious disadvantages with the most common treatments.
Limitations and costs of current treatments for skin cancers pose many shortfalls and many patients afflicted with these diseases do not seek proper treatment, resulting in increased morbidity and mortality [1, 3, 4]
An ideal skin cancer therapy would be one that when applied topically to an exposed skin cancer it selectively necrotizes the tumour cells or induces them to undergo apoptosis or necrosis without causing damage to the surrounding healthy skin cells. In practice this has long eluded cancer therapy. The anticancer drugs available are neither selective nor penetrative.
Existing antimitotic chemotherapeutic agents appear to affect fast growing cells by killing such cells when they are dividing (proliferating cells). When such cells are not dividing (non-proliferating cells) the existing antimitotic chemotherapeutic agents have very limited effects upon these cells. Consequently, the time course for treating cancer cells with existing anti-mitotic chemotherapeutic agents is long and repetitive treatments are required. In addition, certain cancers have developed drug-resistance which seriously complicates antimitotic therapy. The side effects of antimitotic chemotherapy are well know.
Curaderm BEC5
Curaderm BEC5 topical cream contains the antineoplastic agents SRGs known as BEC.
BEC is a mixture of solasodine glycosides consisting of the triglycosides solasonine (β-solatriose) (33%), solamargine (β-chacotriose) (33%), and di-and monoglycosides (34%). All the glycosides contain the same aglycone, solasodine [1, 3, 4].
Figure 1 shows the chemical structures of solasonine and solamargine.
Figure 1. Chemical structures of solasonine and solamargine
SGRs are very promising antineoplastics. Oral, intravenous, intraperitoneal and intralesion studies with these glycoalkaloids have been described [5-11]. Many studies have reported the high antineoplastic efficacy, low toxicity of solamargine, solasonine and a constant mixture of these glycoalkaloids (BEC).
The cream formulation Curaderm BEC5 is available to patients in several countries. CuradermBEC5 contains the glycoalkaloids BEC at 0.005% as a topical cream formulation. The cream is applied twice daily (when possible every 12 hours) under occlusive dressing (micropore paper tape) until the lesion has clinically regressed [1, 3, 4].
The mode of action of Curaderm BEC5
Unlike established antimitotic drugs, BEC and its individual glycoalkaloids, solamargine and solasonine, are not antimitotic in their actions. BEC, at the appropriate dose, only interacts with cancer cells and not with normal cells.
A specific protein has been identified on cancer cells. This protein, known as rhamnose binding protein, is not, or very limited, on normal cells. The rhamnose binding protein is a receptor on cancer cells and binds BEC. After internalization in the cancer cell by receptor-mediated endocytosis through “coated pit endocytosis” a receptorsome or endosome is formed. Gradual transformation of endosomes results in the formation of lysosomes. BEC then triggers extrinsic and intrinsic apoptotic pathways in the cancer cells by up-regulating the expressions of external death receptors, such as tumour necrosis factor receptor 1 (TNFR-1), Fas receptor, TNFR-1 associated death domain and Fas-associated death domain. BEC enhances the intrinsic ratio of Bax to Bcl-2 by up-regulating Bax and down-regulating Bcl-2 and Bcl-xL expressions. These effects result in activation of Caspase -8, -9 and -3 in cancer cells, indicating that BEC triggers extrinsic and intrinsic apoptotic pathways in cancer cells [1, 3, 4].
Apoptosis or programmed cell death is a highly organized physiological process that results in the removal of unwanted cells. Induction of apoptosis in cancer cells or malignant tissues is accepted as an efficient approach for cancer chemotherapy.
The Therapeutic Agents in Curaderm BEC5 are More Effective and Safer than Other Well Established Drugs
It has been reported that solamargine the main constituent of BEC as an anticancer agent is far more effective than taxol, cisplatin, gemcitabine, camptothecin, vinblastine, methotrexate, 5-fluorouracil, epirubicin and cyclophoshamide [11].
Safety of Curaderm BEC5
Studies with Curaderm BEC5 have demonstrated that there are no adverse effects on the liver, kidneys or haematopoietic system during treatment [1, 3, 4].
When Curaderm BEC5 cream is applied to lesions on the skin, the action of Curaderm BEC5produces the following pattern of response: first erythema, then, usually, erosion, ulceration, dying of treated targeted cells and regrowth of normal cells. No systemic absorption of BEC occurs [12-14].
The reported local adverse reactions are itching, pain and occasionally burning sensation at the site of application. The local adverse reactions which are transient, are due to excipients salicylic acid and urea in the Curaderm BEC5 cream [4, 12].
Curaderm BEC5 is Noninvasive by Simple Topical Application of a Cream
The reported recommended Curaderm BEC5 treatment procedure is as follows:
The lesion and surrounding area is washed with a mild, non-irritating, soap, rinsed with water and dried thoroughly. A thin layer of approximately 2mm thick of Curaderm BEC5 is applied to the lesion. The lesion is then covered with an occlusive dressing such as micropore tape. During treatment the lesion is continually covered with the micropore dressing as the lesion is not allowed to dry out to form a scab. Application of Curaderm BEC5 is continued until the lesion is completely ablated and replaced with normal skin. At least twice daily application is necessary. Treatment period depends on the type and size of the lesion and accordingly, varies from a few days to several months. Clinical observations reveal that initially the lesion size appears to increase significantly and as treatment progresses the size of the lesion decreases until it is completely ablated and replaced with normal skin cells.
Curaderm BEC5 Shows Superior Cosmetic Outcomes Compared With Other Available Treatments
One of the unfortunate after-effects of the most widely used skin cancer treatments is that they often leave scars after treatments. Because many skin cancers crop up on parts of the body that are most exposed to the sun, having a carcinoma on the face – and scar after treatment – is very common. Understanding that treating skin cancer by most procedures may result in scars or disfigurement can also be troubling.
The mode of action of BEC places Curaderm BEC5 in an excellent enigmatic position. Consequently, treatment of skin cancer with Curaderm BEC5 exhibits excellent cosmetic end results with no or little scarring.
A unique case where a direct comparison could be made between the cosmetic effects of surgery and Curaderm BEC5 treatment was previously reported [7]. Other studies have verified the non-comparable cosmetic outcomes of Curaderm BEC5 therapy. Most recently studies were published whereby the huge benefit in terms of cosmetic outcomes of Curaderm BEC5 therapy was shown [11-15].
Examples Of Treatment Cases With Curaderm BEC5
Figures 2-13 illustrate some examples of cosmetic outcomes of various skin cancer treatments with Curaderm BEC5.
Figure 2. Clinical diagnosis of a BCC on the nose of a patient before treatment with Curaderm (a), during therapy (b) and site of treated BCC after completion of therapy (c) [14].
Figure 3. Clinical progress of a BCC close to the eye of the patient before treatment (a), during therapy (b), and site of treated BCC after completion with Curaderm (c) [14].
Figure 4. Large BCC on the temple of a woman (a). This BCC had been surgically removed and skin grafts applied on two previous occasions only to return. Four weeks treatment with Curaderm resulted in full regression (b). Note the cosmetic result. The clinical diagnosis was confirmed histologically by punch biopsy (c). After completion of the therapy histopathology determined that no residual cancer was present (d). Clinical assessment 5 years post treatment revealed that there was no recurrence [14].
Figure 5. An extensive protruding (4cm x 4cm x 2cm) BCC with central ulceration and raised curly borders on the right side of his face next to his ear is seen in this patient (top row). Treatment with Curaderm resulted in rapid break-down of the tumour and after 2 weeks of treatment the lesion was reduced to about a half of the original size. Minor bleeding had occurred during this treatment period (middle row). After 14 weeks of treatment the lesion was clinically eliminated. Normal skin cells had replaced the tumour and the cosmetic end result was excellent, with no scar tissue formation. Even the hairs had regrown where the tumour was originally (bottom row) [3].
Figure 6. A BCC of approximately 3cm x 4cm x 0.5cm before (a), during (b) and after (c) Curaderm BEC5 topical treatment. Complete clinical remission was observed 14 weeks after topical Curaderm BEC5 treatment [4].
Figure 7. BCC of approximately 3cm x 3cm x 0.5cm before treatment (a), during treatment (b) and after (c) Curaderm BEC5 topical treatment. After 14 weeks of topical application with Curaderm BEC5 the entire lesion had completely regressed [4].
Figure 8. A large BCC with three distinct focal areas measuring approximately 4cm x 4cm (a). During Curaderm BEC5 topical application erosion of the entire area occurred and it can be seen that the original distinct areas constituted a large interconnected BCC (b). The entire lesion was eliminated after treatment (c). Treatment with Curaderm BEC5 topical application was for 14 weeks [4].
Figure 9. A protruding (a), large (b) BCC of approximately 1cm x 3cm x 3cm before treatment. Haemorrhagic necrosis of the tumour mass occurred during treatment with Curaderm BEC5 (c). After 14 weeks of Curaderm BEC5 topical application the lesion had completely regressed. The impressive cosmetic end result (d) is seen 16 weeks after commencement of Curaderm BEC5therapy [4].
skin. Continue to treat lesion with Curaderm BEC5t are well withing the eipidermis and dermis, causing an apparent hole in th
Figure 10.A very large SCC, 6cm in diameter, before (a); during (b-d), and after (e) treatment with Curaderm. The treatment period was for 12 weeks. Note the specificity of Curaderm for the cancer cells and the regrowth of normal cells during Curaderm therapy. The clinical diagnosis was confirmed histologically by punch biopsy (f). After completion of the therapy histopathology determined that no residual cancer was present (g). Clinical assessment 5 years post treatment revealed that there was no recurrence [12].
Figure 11. Clinical and histological diagnosis of an SCC on a leg of a patient before treatment (lane a), during therapy (lane b) and site of treated SCC after completion of therapy (lane c). 1. Clinical diagnosis; 2. Histological diagnosis. Arrows indicate cancer cells dying during Curaderm treatment (lane B2). The observation of this type of cell death caused by Curaderm is similar to those obtained in cell culture studies [3, 14].
Figure 12. A large SCC (approximately 8cm x 6cm) on the shoulder of a patient before (a), during (b) and after (c) treatment with Curaderm. After 10 weeks the tumour was completely healed. The clinical diagnosis was confirmed histologically by punch biopsy (d). After completion of the therapy histopathology determined that no residual cancer was present (e). Clinical assessment 5 years post treatment revealed that there was no recurrence [12].
Figure 13. SCC on the nose of a patient before (a), during (b) and after Curaderm treatment (c). Curaderm was applied for 5 weeks. Note the depth of the cancer as cartilage was exposed during treatment. The clinical diagnosis was confirmed histologically by punch biopsy (d). After completion of the therapy histopathology determined that no residual cancer was present (e). Clinical assessment 5 years post treatment revealed that there was no recurrence [12].
Health versus cosmetic outcomes with Curaderm BEC5 have additional benefits. The treatment procedure is easily performed as an outpatient treatment. The procedure is non-invasive with excellent cosmetic outcomes such as no, or very little scarring, improved colouring, texture and tone of the skin.In most cases it is not possible to identify where the skin cancers were after Curaderm BEC5 treatment. The results are permanent if proper instructions are followed as shown with follow-up studies for over a decade [1, 4, 12].
Discussion
SRGs and thus BEC are a new class of antineoplastic chemotherapeutic agents. BEC is extracted from various Solanum plant materials and expresses its antineoplastic activities by highly ordered specificity and cancer cell destroying ability due to apoptosis and oncosis triggered by extrinsic and intrinsic apoptotic pathways. It has also been reported that BEC or its individual component solamargine is far more effective than other established antineoplastics-taxol, cisplatin, gemcitabine, camphothecin, vinblastine, methotrexate, 5-fluorouracil, epirubicin and cyclophosphamide.The fact that CuradermBEC5 eliminates BCCs is confirmedby many other published studies. The cosmetic end results after CuradermBEC5 therapy are, as previously reported, excellent. CuradermBEC5 therapy removes smaller BCCs within 6 weeks of treatment and for larger BCCs it takes approximately 14 weeks.
Tissue-sparing and preservation of functionality
CuradermBEC5 successfully treats Bowen’s disease (SCC in situ) of the penis (figures14, 15) with preservation of functionality and sparing of tissue. Treatment of these tumours with CuradermBEC5 is superior to other more-destructive treatment options for Bowen’s disease of the penis [12, 16].
Figure 14. An intra-epithelial SCC on the penis of a patient before (a), during (b) and after Curaderm therapy (c). The prognosis of this patient before treatment with Curaderm was amputation. Treatment period was 6 weeks. The clinical diagnosis was confirmed histologically by biopsy (d). After completion of the therapy histopathology determined that no residual cancer was present (e). Clinical assessment 5 years post treatment revealed that there was no recurrence [12].
Figure 15. Bowen’s disease on the penis (a), two months after starting treatment with a standard mixture of solasodine glycosides (b), Nine months after starting treatment with a standard mixture of solasodine glycosides (c), Two year follow-up after completion of treatment with a standard mixture of solasodine glycosides. Liquid nitrogen was used to treat verrucous lesions[16].
Conclusion
A topical cream, Curaderm BEC5, containing these antineoplastic glycoalkaloids, is very effective and safe for the treatment of nonmelanoma skin cancers. The treatment of skin cancers with Curaderm BEC5 overcomes the major drawbacks of other currently available therapies. Curaderm BEC5 is specific and eliminates the cancer cells only, without harming normal cells and consequently the cosmetic end result is excellent.
Studies of topical application of CuradermBEC5 have now been reported for malignant lesions on the face, trunk, limbs and penis. During treatment, patients develop areas of inflammation in and around the tumour, which then usually necrose, leading to ulceration and healing by
re-epithelialization. The endpoint of therapy is achieved with regrowth of new skin at the treatment site with unthinkable cosmetic outcomes.
REFERENCES
[1] T. R. Chase, “Curaderm BEC5 for Skin Cancers, Is It? An Overview,” Journal Cancer
Therapy, Vol. 2, No. 5, 2011, pp. 728-745.
doi:10.4236/jct.2011.25099
[2] H. W. Rogers, N. A. Weinstock, A. R. Harris, M. R.Hinckley, S. R. Feldman, A. B.
Fleischer and B. M.Coldiron, “Incidence Estimate of Nonmelanoma SkinCancer in the
United States,” Archives of Dermatology,Vol. 146, No. 3, 2010, pp. 283-287.
doi:10.1001/archdermatol.2010.19
[3] B. E. Cham, “Topical SolasodineRhamnosyl Glycosides Derivedfrom the Eggplant
Treats Large SkinCancers:Two Case Reports,” International Journal of Clinical
Medicine, Vol. 2, 2011, pp. 473-477.
doi:10.4236/ijcm.2011.24080
[4] B. E. Cham, “Intralesion and CuradermBEC5 Topical Combination Therapies of
Solasodine Rhamnosyl Glycosides Derived from the Eggplant or Devil’s Apple Result in
Rapid Removal of Large Skin Cancers. Methods of Treatment Compared,” International
Journal of Clinical Medicine, Vol. 3, 2012, pp. 115-124.
doi:10.4236/ijcm.2012.32024
[5] M. Millward, A. Powell, P. Daly, S. Tyson, R. Ferguson and S. Carter, “Results of Phase
I Clinical Trials of Coramsine in Patients with Advanced Solid Tumors,” Journal
Clinical Oncology, Vol. 2, No. 18, 2006, p. 2070.
[6] B. E. Cham, “SolasodineRhamnosyl Glycosides Specifically Bind Cancer Cell
Receptors and Induce Apoptosis and Necrosis. Treatment for Skin Cancer and Hope for
Internal Cancers,” Research Journal Biological Sciences, Vol. 2, No. 7, 2007, pp. 503-514.
[7] B. E. Cham and T. R. Chase, “SolasodineRhamnosyl Glycosides Cause Apoptosis in
Cancer Cells. Do They Also Prime the Immune System Resulting in Long-Term
Protection Against Cancer?” PlantaMedica, Vol. 78, 2012, pp. 349-353.
doi:10.1055/s-0031-1298149
[8] B. E. Cham, “Cancer Intralesion Chemotherapy with SolasodineRhamnosyl Glycosides,”
Research Journal Biological Sciences,Vol. 3, 2008, pp. 1008-1017.
[9] R. G. Van der Most, R. Himbeck, S. Aarens, S. J. Carter, I. Larma, C. Robinson, A.
Currice and R. A. Lake, “An-titumor Efficacy of the Novel Chemotherapeutic Agent
Coramsine Is Potentiated by Cotreatment with CpG- Containing Oligodeoxynucleotides,
Journal Immunotherapy, Vol. 29, No. 2, 2006, pp. 134-142.doi:10.1097/01.cji.0000187958.38179.a9
[10] B. E. Cham, “Cancer Intralesion Chemotherapy with SolasodineRhamnosyl
Glycosides,” Research Journal Biological Sciences, Vol. 3, 2008, pp. 1008-1017.
[11] K. W. Kuo and C. N. Lin, “Pharmacological Composition for Treating Cancer Cells,”
United States Patent 6, 1999, pp. 214-803.
[12] B. E. Cham, “SolasodineRhamnosyl Glycosides in a Cream Formulation Is Effective for
Treating Large and Troublesome Skin Cancers,” Research Journal Biological Science,
Vol. 2, No. 7, 2007, pp. 749-761.
[13] B. E. Cham, B. Daunter and R. Evans, “Topical Treatment of Malignant and
Premalignant Skin Cancers by Very Low Concentration of a standard mixture of
Solasodine Glycosides,” Cancer Letters, Vol. 59, No. 3, 1991, pp. 183-192.
[14] B. E. Cham and H. M. Meares, “Glycoalkaloids from Solanumsodomaeum L. are
Effective in the Treatment of Skin Cancers in Man,” Cancer Letters, Vol. 36, No. 2,
1987, pp. 111-118.
doi:10.1016/0304-3835(87)90081-4
[15] S. Punjabi, L. J. Cook, P. Kersey, R. Marks and R. Cerio, “SolasodineGlycoalkaloids: A
Novel Topical Therapy for Basal Cell Carcinoma.A Double-Blind, Randomized,
Placebo-Controlled, Parallel Group, Multicentre Study,” International Journal
Dermatology, Vol. 47, No. 1, 2008, pp. 78-82.
doi:10.1111/j.1365-4632.2007.03363.x
[16] L. H. Goldberg, J. M. Landau, M. N. Moody and I. J. Vergilis-Kalner, “Treatment of
Bowen’s Disease on the Penis with Low Concentration of a Standard Mixture of
Solasodine Glycosides and Liquid Nitrogen,” Dermatologic Surgery, Vol. 37, No. 6,
2011, pp. 858-861.
doi:10.1111/j.1524-4725.2011.02014.x