Next Generation PDT

Photodynamic therapy is effective not only in treating cervical intraepithelial neoplasia (CIN) but also for eradicating cervical human papilloma virus (HPV), a causal factor in the formation cancer. Many of the common surgical procedures for cervical cancer lead to infertility and significantly PDT has the potential to preserve fertility while simultaneously successfully treating the cancer. Patients are not informed of this option in the treatment of their cervical cancer which can preserve fertility they are significantly disadvantaged.

Breast Cancer
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Photodynamic therapy offers a highly successful treatment for recurrent breast cancer on the chest wall with few side effects, high patient satisfaction, quality of life and possible repetitive application. PDT using m-THPC (a medicine approved for use in Europe) resulted in complete response (no evidence of residual tumor) in all patients treated for recurrent breast cancer.

Lung Cancer
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Photodynamic therapy (PDT) has now achieved the status of a standard treatment modality for centrally located, early-stage lung cancer and is introduced on the home page of the US National Cancer Institute. As an increasing number of patients consider quality of life after therapy, the indications for PDT are expected to expand. PDT is a promising new technique for curative treatment of localized, peripheral lung cancer less than 1cm in size in patients who are unfit for surgery or radiotherapy.

Prostate Cancer
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Photodynamic therapy has great potential in the treatment of prostate    carcinoma. The principle side effects of prostate surgery are incontinence and impotence. These can be potentially avoided with PDT. However, most patients are not even informed of the option nor are offered the therapy.

Esophagus Cancer
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PDT is an effective and safe treatment method in esophageal cancer. In advanced disease it improves swallowing. In early stage disease it offers long survival and the prospect of cure in some patients.

Peritoneal/Sarcoma
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Debulking surgery with intraperitoneal PDT for sarcomatosis is feasible. Preliminary response data suggest prolonged relapse-free survival in some patients.

Skin Cancer
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With a single course of verteporfin (an approved medicine) PDT showed treatment benefit for patients with multiple nonmelanoma skin cancers.

Bile Duct Cancer
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Photodynamic therapy (PDT) of bile duct cancer have shown astonishingly good results in the reduction of cholestasis, improvement of quality of life, and even prolongation of the survival time. In one of the articles the study was terminated prematurely because PDT proved to be so superior to simple stenting treatment that further randomization was deemed unethical. Yet this therapy is offered to no one and is not even mentioned to most patients with bile duct cancer.

Stomach Cancer
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PDT was found to be a safe, feasible treatment that could improve symptoms resulting from advanced gastric cancer.

Brain Cancer
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The selectivity of the process makes PDT appealing in the brain, where conservation of healthy tissue is vital. Many new photosensitizing compounds and varying methods of light delivery are being studied. This technology shows promise for the treatment of primary brain malignancies.

Cutaneous Lymphoma
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The results showed a high response of both stage I and stage III MF lesions to ALA PDT. This modality appears to be very effective and can be used successfully for MF treatment.

Liver Metastases
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With the use of multiple devices, ablation of liver tumors seems to be possible, and no severe side effects or toxicities related to the treatment are reported. PDT can become a clinically relevant adjunct in the locoregional therapy strategies.   Another study demonstrates that mTHPC (an approved medicine in Europe) is retained in an intrahepatic tumour and that mTHPC-PDT is capable of inducing complete tumour remission of liver tumours. Again, amazingly few if any patients are being informed of this option, much less being offered the therapy.

Malignant Melanoma
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PDT with chlorin e(6) for skin metastases from melanoma is effective and well tolerated. Further clinical investigation of PDT with chlorin e(6) is warranted.

Bladder Cancer
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More than half of the patients with TCC refractory to traditional intravesical therapy received benefit from a single PDT session. Patients who achieve a complete recovery (CR) have less likelihood of and longer time interval before needing cystectomy for progressive disease than no response (NR) patients. The PDT protocol is associated with minimal morbidity in these high-risk patients.

Ovarian Cancer
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These preliminary results suggest that PDT with an OC125 immunoconjugate may be an effective therapy for the management of advanced ovarian cancer. Clinical application of this therapy needs to be further optimised and may require multiple treatments, similar to fractionated radiation therapy and cyclic chemotherapy, in order to control malignant disease with acceptable toxicity to normal tissue. Examples of benefits are as follows: Of the 51 patients enrolled and treated with IP PDT two are alive without evidence of recurrence. Eleven of 45 patients showed no evidence of recurrence 3 months after treatment. No evidence of recurrence was noted in 7/17 sarcoma patients, 2 of 13 ovarian cancer patients, and 2 of 15 gastrointestinal cancer patients.

Pancreas Cancer
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ICG PDT induces consistent and dramatic pancreatic cancer cell death. Since neither ICG nor laser alone caused toxicity, combination therapy may offer effective control of tumor growth with minimal side effects in patients with unresectable primary or metastatic pancreatic cancer

Barretts Esophagus (Pre Malignant condition of the esophagus)
(See corresponding scientific articles)

PDT increases life expectancy and is cost-effective when compared to endoscopic surveillance and surgical esophagectomy. Again, this therapy is not mentioned to most patients and again not offered as therapy in spite of the proven benefits.

Head and Neck Cancer
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In 25 (86%) of 29 tumors, a complete remission of the primary tumor was obtained. In the 4 recurrences, salvage was achieved by conventional therapy. In none of the patients was any long-term functional deficit detected. CONCLUSIONS: This study confirms that PDT is a powerful treatment modality that could be considered as an alternative to surgery or radiotherapy in specific cases of head and neck cancer. The major advantage of PDT over these conventional therapies is the reduction in long-term morbidity. Radiotherapy or surgery could be reserved for salvage therapy in the event of a recurrence or second primary tumors. Often surgery for head and neck cancer leaves the patient with grotesque cosmetic side effect and severe functional speech disabilities. Most if not all of these patients have not been informed of this option nor give the choice of this much less invasive and destructive therapy.

Rectal Cancer
(See corresponding scientific articles)

In a group of patients who are at high risk for recurrence irrespective of initial treatment, PDT can be used as a successful alternative to surgical excision for anal carcinoma in situ. Surgery in this area can lead to lifelong problems with incontinence. Most patients are again not given the option of this less invasive therapy nor even informed of its existence.

General
(See corresponding scientific articles)

PDT can lead to specific tumor auto vaccination that is neither possible nor observed with traditional therapies. It is hypothesized that PDT destroys the structure of a tumor, thereby enabling direct interaction between immune cells and tumor cells resulting in the systemic anti-tumor immune response.

The scientific evidence for the effectiveness of PDT with specific journal references is shown in the following exhibits.

Abstract from Medline: return to Search Results

Int J Clin Oncol, October 1, 2003 ; 8(5): 322-5.

Eradication and reinfection of human papillomavirus after photodynamic therapy for cervical intraepithelial neoplasia.

H Ichimura, S Yamaguchi, A Kojima, T Tanaka, K Niiya, M Takemori, K Hasegawa, and R Nishimura

Department of Obstetrics and Gynecology, Hyogo Medical Center for Adults, 13-70 Kitaoji-cho, 673-8558, Akashi, Japan.

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Articles in Medline by Author:

	Ichimura, H
	Yamaguchi, S
	Kojima, A
	Tanaka, T
	Niiya, K
	Takemori, M
	Hasegawa, K
	Nishimura, R

MEDLINE ABSTRACT

BACKGROUND: Photodynamic therapy (PDT) has been proven to be a promising therapeutic modality for selected dysplasias and malignancies in a variety of organs. We assessed the effectiveness of PDT for treating cervical intraepithelial neoplasia (CIN) by cytological and histological examinations and investigated its impact on human papillomavirus (HPV) infection. METHODS: A series of 31 patients with CIN (2 with CIN2, 29 with CIN3) were given polyhematoporphyrin ether/ester (PHE) 2 mg/kg IV. After 60 h their cervices were exposed to a 630-nm YAG-OPO laser. HPV-DNA extracted from cervical smears was amplified by the polymerase chain reaction and typed for HPV using restriction fragment length polymorphism. RESULTS: At 3 months after PDT, cytology and directed biopsy of the cervix revealed regression of the disease in 28 [complete remission (CR) rate 90%] of 31 patients, and HPV-DNA could be no longer detected in the cervical smears of 22 (76%) of 29 HPV-positive patients. After 12 months, all 31 patients had achieved a CR on biopsy, although HPV-DNA was still present in the cervical smears of 6 patients. The types of HPV-DNA detected 12 months after PDT were different from those seen before PDT in each of the 6 patients, suggesting that they might be reinfected with other HPV types after PDT. CONCLUSION: PDT is effective not only in improving the cytological and histological measures when treating CIN but also for eradicating cervical HPV.

Abstract from Medline: return to Search Results

Lasers Surg Med, January 1, 2002; 30(4): 273-9.

Photodynamic therapy of vulvar and vaginal condyloma and intraepithelial neoplasia using topically applied 5-aminolevulinic acid.

MK Fehr, R Hornung, A Degen, VA Schwarz, D Fink, U Haller, and P Wyss

Department of Obstetrics and Gynecology, Division of Gynecology, University Hospital, CH-8091 Zurich, Switzerland. Mathias.Fehr@fhk.usz.ch

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Articles in Medline by Author:

	Fehr, MK
	Hornung, R
	Degen, A
	Schwarz, VA
	Fink, D
	Haller, U
	Wyss, P

MEDLINE ABSTRACT

BACKGROUND AND OBJECTIVES: To determine the feasibility of photodynamic therapy (PDT) of vulvar and vaginal condyloma and intraepithelial neoplasia (VIN, VAIN) and to compare PDT results with conventional treatments. STUDY DESIGN/MATERIALS AND METHODS: Thirty-eight patients with vulvar or vaginal intraepithelial neoplasia (VIN) grade II/III (n = 22) or condyloma (n = 16) had 10% 5-aminolevulinic acid (ALA)-gel applied topically. After 2-4 hours, 80-125 J/cm(2) laser light at a wavelength of 635 nm was applied. PDT was compared to conventional treatments for condyloma (CO(2) laser evaporation) and for VIN III (laser evaporation, surgical excision). RESULTS: The complete clearance rate for condyloma treated by PDT was 66% and the rate for IN was 57% (as determined by biopsy). Of the neoplasia patients, none with hyperkeratotic VIN (n = 4) responded, and only one of four with increased pigmentation cleared. No scarring occurred, and postoperative discomfort lasted 4.9 /- 3.4 days. Reduced disease-free survival (DFS) was associated with multifocal VIN (P = 0.02, OR 2.17, 95% CI 1.15-4.08), but DFS did not vary with treatment mode. CONCLUSIONS: Although PDT is not equally efficacious for all subgroups, PDT for condyloma and intraepithelial neoplasia appears to be as effective as conventional treatments, but with shorter healing time and excellent cosmetic results.

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Int J Cancer, September 1, 2001; 93(5): 720-4.

Photodynamic therapy of locoregional breast cancer recurrences using a chlorin-type photosensitizer.

P Wyss, V Schwarz, D Dobler-Girdziunaite, R Hornung, H Walt, A Degen, and M Fehr

Department of Obstetrics and Gynecology, University Hospital, Z|rich, Switzerland. Pius.Wyss@fhk.usz.ch

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Articles in Medline by Author:

	Wyss, P
	Schwarz, V
	Dobler-Girdziunaite, D
	Hornung, R
	Walt, H
	Degen, A
	Fehr, M

MEDLINE ABSTRACT

Chest wall recurrences are a frequent problem in patients treated by mastectomy for breast cancer. Surgery and ionizing radiation are established treatment modalities in these cases. Photodynamic therapy (PDT) provides an alternative treatment modality using a photosensitizer and laser light to induce selective tumor necrosis. PDT was performed as compassionate use in 7 patients aged 57.6 years ( /-12.6 SD). A total of 89 metastatic skin nodes were treated in 11 PDT sessions. As photosensitizer meta-tetra(hydroxyphenyl)chlorin (m-THPC) was applied intravenously. Patients (n = 3) photosensitized with a drug dose of 0.10 mg/kg bodyweight were irradiated 48 hr after drug application at a lightdose of 5 J/cm(2). Patients (n = 4) were illuminated by an optical dose of 10 J/cm(2) 96 hr after photosensitization with 0.15 mg/kg. Laser light at a wavelength of 652 nm was generated by a diode laser and applied by a front lens light diffuser using a fluence rate of 20--25 mW/cm(2). PDT using m-THPC resulted in complete response in all patients. Response to treatment did not differ when using the 2 different drugdose protocols. Healing time depended mainly on the size of the illumination field but not on the lightdose. Pain score usually raised 1 day after PDT and lasted at higher levels for about 10 days. Healing time usually ranged between 8--10 weeks. Photodynamic technique offers a minimal-invasive, outpatient treatment modality for recurrent breast cancer on the chest wall with few side effects, high patient's satisfaction and with possible repetitive application.

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