Background: Few pancreatic cancers are suitable for surgery and few respond to chemoradiation. Photodynamic therapy produces local necrosis of tissue with light after prior administration of a photosensitising agent, and in experimental studies can be tolerated by the pancreas and surrounding normal tissue. Aims: To undertake a phase I study of photodynamic therapy for cancer of the pancreas. Patients: Sixteen patients with inoperable adenocarcinomas (2.5–6 cm in diameter) localised to the region of the head of the pancreas were studied. All presented with obstructive jaundice which was relieved by biliary stenting prior to further treatment. Methods: Patients were photosensitised with 0.15 mg/kg meso-tetrahydroxyphenyl chlorin intravenously. Three days later, light was delivered to the cancer percutaneously using fibres positioned under computerised tomographic guidance. Three had subsequent chemotherapy. Results: All patients had substantial tumour necrosis on scans after treatment. Fourteen of 16 left hospital within 10 days. Eleven had a Karnofsky performance status of 100 prior to treatment. In 10 it returned to 100 at one month. Two patients with tumour involving the gastroduodenal artery had significant gastrointestinal bleeds (controlled without surgery). Three patients developed duodenal obstruction during follow up that may have been related to treatment. There was no treatment related mortality. The median survival time after photodynamic therapy was 9.5 months (range 4–30). Seven of 16 patients (44%) were alive one year after photodynamic therapy. Conclusions: Photodynamic therapy can produce necrosis in pancreatic cancers with an acceptable morbidity although care is required for tumours invading the duodenal wall or involving the gastroduodenal artery. Further studies are indicated to assess its influence on the course of the disease, alone or in combination with chemoradiation.

Interstitial photodynamic therapy (IPDT) is a technique for applying photodynamic therapy (PDT) to internal tumours using light delivered via fibres inserted percutaneously. This phase I–II study assessed the safety and efficacy of IPDT for patients with persistent or recurrent head and neck cancer unsuitable for further treatment with surgery, radiotherapy or chemotherapy, recruited for ‘last hope’ salvage treatment. Patients were sensitised with 0.15 mg kg⁻¹ mTHPC (meso-tetrahydroxyphenyl chlorin) 4 days prior to light delivery from fibres inserted directly into the target tumour (20 J per site at 652 nm) under image guidance. In all, 45 patients were treated. Nine achieved a complete response. Five are alive and free of disease 10–60 months later. Symptomatic relief (mainly for bleeding, pain or tumour debulking) was achieved in a further 24. The median survival (Kaplan–Meier) was 16 months for the 33 responders, but only 2 months for the 12 nonresponders. The only serious complication was a carotid blow out 2 weeks after PDT. No loss of function was detected in nerves encased by treated tumours. Interstitial photodynamic therapy provides worthwhile palliation with few complications and occasional long-term survivors for otherwise untreatable advanced head and neck cancers. It is a treatment option worth adding to those available to integrated head and neck oncology teams.

Photodynamic therapy (PDT) is a technique for producing localized necrosis with light after prior administration of a photosensitizing agent. This study investigates the nature, safety, and efficacy of PDT for image-guided treatment of primary breast cancer. We performed a phase I/IIa dose escalation study in 12 female patients with a new diagnosis of invasive ductal breast cancer and scheduled to undergo mastectomy as a first treatment. The photosensitizer verteporfin (0.4 mg/kg) was administered intravenously followed by exposure to escalating light doses (20, 30, 40, 50 J; 3 patients per dose) delivered via a laser fiber positioned interstitially under ultrasound guidance. MRI (magnetic resonance imaging) scans were performed prior to and 4 days after PDT. Histological examination of the excised tissue was performed. PDT was well tolerated, with no adverse events. PDT effects were detected by MRI in 7 patients and histology in 8 patients, increasing in extent with the delivered light dose, with good correlation between the 2 modalities. Histologically, there were distinctive features of PDT necrosis, in contrast to spontaneous necrosis. Apoptosis was detected in adjacent normal tissue. Median follow-up of 50 months revealed no adverse effects and outcomes no worse than a comparable control population. This study confirms a potential role for PDT in the management of early breast cancer.

Multiple drug resistance (MDR) is a problem that seriously reduces the efficacy of many chemotherapy agents. One mechanism for MDR is increased acidification of endocytic vesicles and increased cytosol pH, so weak base chemotherapeutic agents, including doxorubicin, are trapped in endocytic vesicles and exhibit a drug resistant phenotype. Treatments that selectively reverse this accumulation may therefore reverse the MDR phenotype. Photochemical internalization (PCI) is a novel technology developed for site‐specific enhancement of the therapeutic efficacy of macromolecules by selective photochemical rupture of endocytic vesicles and consequent release of endocytosed macromolecules into the cytosol. This study evaluates PCI for release of doxorubicin from endocytic vesicles in MDR cells. Two breast cancer cell lines, MCF‐7 and MCF‐7/ADR (the latter resistant to doxorubicin), were selected. They were found equally sensitive to photochemical treatment with the photosensitiser TPPS_2a (disulfonated meso‐tetraphenylporphine) and light. On exposure to doxorubicin alone, the IC₅₀ (drug concentration for 50% reduction in colony formation) was 0.1 μM for MCF‐7 and 1 μM for MCF‐7/ADR. After PCI (photochemical treatment followed by doxorubicin), the IC₅₀ concentration was 0.1 μM for both cell lines. Comparable changes were seen with assay of cell viability using 3‐(4,5‐dimethyltiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT). On fluorescence microscopy in MCF‐7/ADR cells, doxorubicin localised in granules identified as lysosomes. After PCI, doxorubicin was released into the cytosol and entered cell nuclei, as was seen in MCF‐7 cells without PCI. In conclusion, PCI reversed the MDR phenotype of doxorubicin resistant breast cancer cells by endo‐lysosomal release of the drug. The technique is a promising new approach to tackling the problem of MDR.

Background: Many patients with advanced malignant dysphagia are not suitable for definitive treatment. The best option for palliation of dysphagia varies between patients. This paper looks at a simple technique for enhancing laser recanalisation. Aim: To assess the value of adjunctive brachytherapy in prolonging palliation of malignant dysphagia by endoscopic laser therapy. Patients: Twenty two patients with advanced malignant dysphagia due to adenocarcinoma of the oesophagus or gastric cardia, unsuitable for surgery or radical chemoradiotherapy. Methods: Patients able to eat a soft diet after laser recanalisation were randomised to no further therapy or a single treatment with brachytherapy (10 Gy). Results were judged on the quality and duration of dysphagia palliation, need for subsequent intervention, complications, and survival. Results: The median dysphagia score for all patients two weeks after initial treatment was 1 (some solids). The median dysphagia palliated interval from the end of initial treatment to recurrent dysphagia or death increased from five weeks (control group) to 19 weeks (brachytherapy group). Three patients had some odynophagia for up to six weeks after brachytherapy. There was no other treatment related morbidity or mortality. Further intervention was required in 10 of 11 control patients (median five further procedures) compared with 7/11 brachytherapy patients (median two further procedures). There was no difference in survival (median 20 weeks (control), 26 weeks (brachytherapy)). Conclusions: Laser therapy followed by brachytherapy is a safe, straightforward, and effective option for palliating advanced malignant dysphagia, which is complementary to stent insertion.

Photodynamic therapy, using a photosensitizing drug activated by red light, can destroy localized areas of cancer with safe healing and without the cumulative toxicity associated with ionizing radiation. We used photodynamic therapy in a phase I-II study to treat patients with locally recurrent prostate cancer after radiotherapy. Patients with an increasing prostate specific antigen (PSA) and biopsy proven local recurrence after radiotherapy were offered photodynamic therapy. Three days after intravenous administration of the photosensitizer meso-tetrahydroxyphenyl chlorin, light was applied using optical fibers inserted percutaneously through perineal needles positioned in the prostate with imaging guidance. Patients were followed with PSA measurements, prostate biopsies, computerized tomography or magnetic resonance imaging and questionnaires on urinary and sexual function. Photodynamic therapy was given to 14 men using high light doses in 13. Treatment was well tolerated. PSA decreased in 9 patients (to undetectable levels in 2) and 5 had no viable tumor on posttreatment biopsies. After photodynamic therapy, contrast enhanced computerized tomography or magnetic resonance imaging showed necrosis involving up to 91% of the prostate cross section. In 4 men stress incontinence developed (troublesome in 2 and mild in 2) which is slowly improving. Sexual potency was impaired in 4 of the 7 men able to have intercourse before photodynamic therapy, which did not improve. There were no rectal complications directly related to photodynamic therapy, but in 1 patient a urethrorectal fistula developed following an ill-advised rectal biopsy 1 month after therapy. Photodynamic therapy is a new option that could be suitable for organ confined prostate cancer recurrence after radiotherapy. With more precise light dosimetry, it may be possible to destroy essentially all glandular tissue within the prostate with few complications. These results suggest that photodynamic therapy merits further investigation.