Presentation on theme: "MELANOMA The responses of cutaneous melanoma have not been sufficiently beneficial to consider PDT a viable option at the present time. Although common."— Presentation transcript:
MELANOMA The responses of cutaneous melanoma have not been sufficiently beneficial to consider PDT a viable option at the present time. Although common sense dictates that melanized cells would be relatively resistant to light- based therapies, lutetium texaphyrin, a photosensitizer activated by very deeply penetrating 752 nm red light, did demonstrate the destruction of subcutaneous melanoma metastases in phase I trials. At present, PDT might only be considered as a final-option, palliative treatment for small cutaneous and subcutaneous metastases of advanced melanoma.
KAPOSI'S SARCOMA In three HIV-infected patients, Kaposi's sarcoma (KSI) was reported to respond to systemic PDT consisting of intravenous indocyanin green (two boluses 30 minutes apart) plus irradiation with an 805 nm diode laser. The lesions irradiated (100 J/cm2) 10-30 minutes after the last dose of indocyanin green demonstrated complete clearance; those treated at longer time intervals between injection and irradiation showed only a partial response.
EXTRAMAMMARY PAGET'S DISEASE In a study of 16 cases of extramammary Paget's disease, 11 of which had received previous treatments (including Mohs micrographic surgery, laser ablation and excision), 8 (50%) showed a complete response at 6 months. However, 3 of these 8 recurred within 1 year, for a durable complete response of 5/16 (31 %). In this protocol, topical ALA 20% was applied to axillary and anogenitallesions and occluded for 18-24 hours. Each lesion received red argon pumped dye laser light (632 nm), followed in some cases by further filtered red light (590-700 nm) irradiation.
PORT-WINE STAINS As noted previously, given the appropriate photosensitizer, PDT has the ability (via LDL receptor-mediated endocytosis) to induce endothelial cell damage and local vascular collapse. Initial clinical studies of PDT alone demonstrated reasonable blanching of PWSs, but the treatment was complicated by the development of skin necrosis when both blue and red light sources were employed. In a series of 118 patients with PWS, one intravenous injection of a purified mixture of six types of porphyrin molecules, followed within 30 minutes by irradiation with a copper vapor laser (578 nm), led to good to excellent clearing in 74% of patients. The highest rate of success was seen in macular PWSs In one small series, PDT, consisting of oral ALA plus PDL, was investigated as a possible treatment for PWSs. No differance
Investigations are ongoing, as PDT has shown to be the only significant alternative to photothermal treatments alone as a means of enhancing the rapidity and degree of PWS improvement.
PSORIASIS In 1937, psoriasis was first reported to respond to PDT consisting of HPD (i.e. porfimer sodium) plus UV light, with seven patients noting a marked improvement. Since then, both systemic (e.g. porfimer, BPD-MA) and topical (ALA) photosensitizers, in combination with visible light, have produced partial or complete clearance of psoriatic plaques. PDT poses an attractive alternative because of the potential for: more rapid clearance of lesions reduced cumulative exposure to UV irradiation (by using photoactivating doses) and the use of visible light: reduce the carcinogenic risk, when compared to traditional UV irradiation therapies.
ACNE Both porphyrin expression by naturally occurring Propionibacterium acnes as well as PplX production occurring primarily within sebaceous glands and hair follicles after topical ALA application have suggested the potential of PDT for diseases of the pilosebaceous unit. PDT utilizing topical ALA and mALA (as well as indocyanine green) may well have an increasing role in the treatment of acne, particularly in patients unable or unwilling to undergo isotretinoin therapy.
HUMAN PAPILLOMAVIRUS INFECTIONS Systemic and topical PDT have led to lesion regression in rabbit models. In addition, some in- vitro studies have pointed to a direct antiviral effect of PDT. As with any cutaneous tumor, topical PDT would be preferred for its lesion specificity and limited photosensitivity. In one study, a maximal condylomata:normal skin PpIX fluorescence ratio was detected at 2 hours, suggesting that virally infected cells could be preferentially targeted by PDT at this same time point. Lastly, because mucosal lesions (i.e. condylomata) typically do not have associated hyperkeratotic scale (which inhibits drug penetration) and cutaneous lesions (i.e. verrucae) are characteristically keratotic, more variable responses to topical PDT would be anticipated with verrucae.
Approved ALA PDT, which utilizes blue light for the treatment of AKs, requires the use of opaque protective goggles as well as placing the face within a relatively confined space illuminated by bright blue light. Some patients may feel' claustrophobic' or find this a stimulus for a panic atta ck.
TECHNIQUE Before any PDT is undertaken, adequate documentation of the lesions to be treated, a full history and informed consent should be obtained. Preoperative photographs are helpful to …. PDT should be carried out in an appropriate clinical setting; it should provide for low light levels (preferably no windows and a dimmer switch or lamp), cooling and ventilating for the heat generated by the light source, and a room whose size is adequate for the necessary equipment. Like any similar situation, the uncomfortable sensations caused by PDT can evoke vasovagal responses. These are largely preventable by instructing patients to eat a moderate meal before therapy, and by prone or supine positioning during intravenous infusions and irradiation.
SYSTEMIC PDT Systemic PDT involves oral or intravenous administration of the drug or prodrug. Porfimer, BPD-MA, SnET2 or mTHPC can be given by a slow, fixed-rate infusion; the time until light application is typically determined with reference to the initiation of the intravenous infusion. When given orally, ALA powder is mixed with orange juice and given either as a single oral bolus or fractionated into 20 mg/kg doses, imbibed hourly. The time until light application is determined with reference to the last oral dose. The patient should be kept in a low-light room to prevent both acute phototoxicity and photobleaching. Because of their rapid and broad distribution, systemic photosensitizers do require more attention to normal skin shielding during irradiation. Patients are given goggles for ocular protection and instructed to avoid bright light exposure.
POSTOPERATIVE CARE peau d'orange appearance Immediately after PDT, the treatment sites develop erythema and edema, often leading to a peau d'orange appearance. Pain typically reduces dramatically with cessation of irradiation. Postoperative pain is usually easily controlled with acetaminophen or non- steroidal antiinflammatory drugs, but some individuals may require opioid analgesics. The patients should again be advised how to avoid photosensitivity reactions by covering themselves with clothing. Those receiving systemic agents should use eyewear that blocks the appropriate wavelengths faithfully until the risk of photosensitivity is minimal.
Wound Healing More superficial epithelial conditions (e.g. AKs, psoriasis, SCCs in situ) may crust and then peel, with newly healed skin appearing within 1-2 weeks. With deeper dermal conditions and photo sensitizers that cause more vascular injury, treated sites first blister or turn gray, then deeper ulcerative wounds develop requiring more prolonged healing times (weeks to months). Patients should keep the wounds moist by applying a topical antibiotic or white petrolatum two to three times a day. Wound infections may occur, but at no greater frequency than with other wounds healing by second intention. Therefore, unless there is a strong propensity to wound infections, patients should only receive antibiotics for identified infections. Patients with a history of HSV infection should receive antiviral prophylaxis if PDT will be administered to the site of a prior infection or an adjacent
PDT has been reported to reactivate photosensitive conditions such as lupus, and the Koebner phenomenon was described after PDT treatment of a superficial SCC in a patient with psoriasis.
This is the most commonly reported side effect of PDT and it can vary from a slight ache to severe pain. The degree of pain depends on the size and anatomic site of the lesion being treated as well as the particular photosensitizer. Comparative study of mALA versus ALA found that the associated pain was less severe with mALA, and the explanation was greater absorption of ALA by cutaneous nerves.
Nausea, emesis, headache and flu-like symptoms. Virtually all macrocyclic photosensitizers are subject to hepatic metabolism, and liver toxicity has occurred with HPD (porfimer sodium). Large (30-40 mg kg) oral doses of ALA may cause a transient (1-3 weeks), dose-dependent elevation of hepatic enzyme and bilirubin levels. However, to date there has been no evidence of permanent liver damage or changes in neurologic function or hematologic indices after oral ALA administration at these doses. More recent experience suggests that ALA dose fractionation (20 mg kg given at hourly intervals) circumvents the elevation of hepatic enzymes.
The future of this highly promising diagnostic and therapeutic technique will depend upon the intricate relationship between technology and clinical medicine. Clinicians should expect advances in light delivery (automated sources with realtime monitoring of dosimetry), photosensitizer development (e.g. indium methyl pyrropheophorbide, a chlorin derivative capable of topical delivery), basic research to elucidate in detail the mechanism of photodynamic action in vivo, and clinical research to establish the safety and efficacy of new photosensitizers as well as to compare proven photosensitizers against standard therapies. Ongoing evaluation of the role of PDT in the treatment of pilosebaceous tumors, lichen planus, morphea, port-wine stain vascular malformations and hirsutism (photodynamic tricholysis), to name just a few.