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complications included one bronchial stenosis, one esophagotracheal
fistula and two probable occult performations of the esophagus. Skin
photosensitization, which was never observed later than the first week
after injection, occurred in 12 patients. Hence, PDT with H2(m-THPC) is a
safe and effective technique for the treatment of early carcinomas of the
upper aerodigestive tract. Its efficacy is much lower for more advanced
cancers. Recently, Dilkes et al.359 have treated a wide variety of head
43 / Porphyrins as Photosensitizers in Photodynamic Therapy
Scheme 84. Barbituric acid derivatives of porphyrins and chlorins.
R = H, X = Î
0 - v 4 Htg"V
Butyl - N' V Me'
^~N 0 | HI C02Me
Bu'y' C02Me C02Me
cancer patients with H2(m-THPC)-mediated PDT. Treatment ranged from
palliation and adjunctive to curative procedures, and the results were
Miravant (Santa Barbara, California), has reported promising
preliminary phase I/Ï clinical results with SnEt2 (tin ethyletiopurpurin)
for the treatment of cutaneous cancers and AIDS-related Kaposi's
sarcoma.172 The first combined phase I/II study on cutaneous cancers
included 46 patients with 418 tumors. Based on the result from phase I
studies, the optimal drug/light dose was used (1.2 mg /kg and 200 J/cm2)
in phase Ï. Complete response with no visible or palpable evidence of the
tumor was obtained in the treatment of all the basal cell carcinomas. The
second combined phase I/II study on AIDS-related Kaposi's sarcoma
included 45 patients with 404 tumors. Phase I investigated with one drug
and one light dose, while phase II was conducted using one drug dose and
two light doses (1.2 mg/kg, 200 and 300 J/cm2). At the higher light
doses, 63% of the evaluable tumors responded including 37.8% complete
response and 25% partial response. Side effects of the treatment were
mild transient sun sensitivity in a small percentage of patients.
BPDMA is currently in phase II clinical trials for the treatment of
cutaneous malignancies (basal-cell carcinoma and cutaneous metastases)
and psoriasis.360 Results to date suggest that BPDMA has potential in
both of these areas. One hundred and twenty patients have received
liposomal BPDMA intravenously in doses ranging between 0.15 and 0.5 mg /
kg. No unexpected adverse events have been attributed to the drug to date
and only one patient has reported a mild case of skin photosensitivity.
The drug-light interval was between 20 minutes and 4 hours post
injection. Recently, a clinical trial was initiate for the treatment of
age-related macular degeneration (AMD), a neovascular condition in the
eye which leads to blindness.361 In the phase I study, 40 patients were
treated with 6 or 12 mg/kg of BPD and single-light treatment of 50, 75,
100 or 150J/cm2 at either 20 or 30 minutes post intravenous injection. No
shortterm adverse events or unexpected loss of visual accurity have been
observed. Results from phase II studies are also very encouraging.
Pandey and Zheng
Scheme 85. Nucleoside adducts of porphyrins and chlorins.
Scheme 86. Oxybenzy- and oxypyridino-porphyrins via the "3 + 1" approach.
424 X = N
425 X = CH
The response rate for basal-cell carcinomas following a single
treatment of ALA following topically ALA-based PDT treatment has been 90%
complete cure and 7.5% partial cure for the first 80 lesions treated.362
The cosmetic results have been excellent, and patient acceptance has been
very good. Since then numerous clinical studies have been carried out.
ALA has been shown to be effective for selective photosensitization
whether administered topically for PDT of cutaneous lesions, locally for
use in internal organs such as the urinary bladder or uterus, or
via oral or parenteral administration for PDT of internal cancers.
DUSA Pharmaceuticals has completed a phase III trial of ALA in actinic
kerotoses and expects FDA approval in
In a phase I clinical study carried out by Weiman et al.364 12
patients with a total of 15 tumor sites were treated with PDT using NPe6.
Lesions included recurrent adenocarcinoma of the breast, basal-cell and
squamous-cell carcinoma. The protocol consisted of a single intravenous
43/Porphyrins as Photosensitizers in Photodynamic Therapy
Scheme 87. Porphyrins containing six-membered ring systems.
Et HO Et
Scheme 88. A novel ring-enlargement reaction for the formation of