Meta-tetra(hydroxyphenyl)chlorin photodynamic therapy in early-stage squamous cell carcinoma of the head and neck

Objective: Photodynamic therapy (PDT) is a relatively new treatment modality for various types of cancer, including cancer of the head and neck. The advent of the second-generation photosensitizers such as meta-tetra(hydroxyphenyl)chlorin (mTHPC) (Foscan; Scotia Pharmaceuticals, Stirling, Scotland), which are more effective and less phototoxic to the skin than their forerunners, now makes this treatment a feasible alternative to surgery or radiotherapy in specific cases. To evaluate the long-term outcome of this therapy for squamous cell carcinomas of the head and neck, we treated patients with PDT using mTHPC. Design: Prospective study. Setting: Tertiary cancer referral center. Patients: Twenty-five patients with 29 T1-T2 N0 tumors of the oral cavity and/or oropharynx. Intervention; Photodynamic therapy. Main Outcome Measure: Complete local tumor remission. Results: The mean follow-up of the patients after treatment was 37 months. 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 tumor

Intraperitoneal Photodynamic Therapy: Comparison of Red and Green Light Distribution and Toxicity

The aim of this study was to compare red (652 nm) and green (514 nm) light for photodynamic therapy (PDT) of the peritoneal cavity with emphasis on light distribution and toxicity. Red-light PDT was limited by intestinal toxicity and it was hypothesized that less penetrating green light would allow higher light doses to be used in the peritoneal cavity. Female non-tumor-bearing rats were photo-sensitized with mTHPC (meta-tetrahydroxyphenylchlorin, Foscan®) intravenously or intraperitoneally and the peritoneum was illuminated using a minimally invasive technique. For both red and green light, the time of illumination was varied to give the required dose. Light fluence rate was measured in situ at multiple sites within the abdominal cavity. The toxicity experiments were carried out with a total of 160 J incident red or 640 J incident green light and a drug dose of 0.15 mg/kg Foscan®. For red light a mean fluence rate of 55.2 ± 38.5 mW cm -2 was measured, with a peak fluence rate of 128 mW cm-2 on the intestines. For green light the mean and peak fluence rates were 8.2 ± 9.0 (i.e. including zero fluence rate measurements) and 28 mW cm-2 respectively. Intestines were most vulnerable to red light illumination. The intravenous injection route resulted in increased toxicity for red light, but for green light there were no major differences between intravenous and intraperitoneal routes. The 4 h interval between drug and illumination resulted in very little toxicity for both wavelengths. We conclude that for intraperitoneal PDT green light allows higher light doses than red light, but the light distribution over the peritoneum is much less favorable and may not be suitable for whole peritoneal illumination using a minimal-access technique

Intraperitoneal photodynamic therapy in the rat: Comparison of toxicity profiles for photofrin and mTHPC

Toxicity studies for intraperitoneal photodynamic therapy (IPPDT) were performed in Wag/RijA rats, using specially designed light delivery blocks for proper light distribution and light dosimetry. A recently developed photosensitizer mesotetrahydroxyphenylchlorin (mTHPC), excited at 652‐nm wavelength, was compared with Photofrin (630 nm). Toxicity profiles for various sensitizer doses, light fluences and time intervals were investigated. A light fluence of 15 J ‐ cm−2 delivered to the entire peritoneum 24 hr after 5 mg Photofrin per kg i.v. induced reversible impairment of intestinal, liver and kidney function. A dose of 0.2 mg mTHPC per kg i.v. followed by 6 J · cm−2 at 72 hr appeared to be equitoxic to the intestines; however, functional tests revealed little effect for this mTHPC‐mediated IPPDT regime on liver or kidney. Histology demonstrated focal irreversible damage to the kidneys for both photosensitizers, not reflected in functional impairment. Light doses of 25 to 30 J. cm−2 at 24 hr after Photofrin or 8–12 J · cm−2, 72 hr after mTHPC caused lethal toxicity in the first 2 weeks due to intestinal damage. Higher light doses caused a shock syndrome and rhabdomyolysis resulting in death within 20 hr for both photosensitizers. In conclusion, maximum tolerable schedules for whole‐abdomen IPPDT were defined for Photofrin and mTHPC. Both photosensitizers cause similar toxicity profiles depending on drug dose, light fluence and time interval