SAN ANTONIOPhotodynamic therapy (PDT) with porfimer sodium (Photofrin) in patients with endobronchial obstruction due to locally advanced lung cancer appears to be at least as good as an Nd-YAG laser for palliation and probably better, Harvey I. Pass, MD, said at a satellite symposium of the Society for Thoracic Surgeons meeting.
Following injection, porfimer sodium (Photofrin) largely clears normal cells but is selectively retained by malignant cells. When the area of malignancy is exposed to light from a nonthermal laser at 630 nm, a photochemical reaction produces a toxic form of oxygen, destroying malignant cells with minimal side effects. At this time, porfimer sodium is the only agent approved for photodynamic therapy (PDT) in the United States.
Patients who receive porfimer sodium become photosensitized and for 30 days must avoid exposure of skin and eyes to direct sunlight or bright indoor light (such as from examination lamps or unshaded bulbs at close proximity). Outdoors, patients should wear sunglasses with an average light transmittance of less than 4%.
Visible light stimulates photo-activation, and, therefore, UV sunscreens do not offer protection. Because exposure to ambient indoor light safely and gradually inactivates remaining drug in the skin, patients should be instructed not to remain in a darkened room.
Dr. Pass, chief of thoracic surgery, Karmanos Cancer Institute, Detroit, presented data from two prospective randomized clinical studies of PDT in patients with obstructing endobronchial non-small-cell lung cancer (NSCLC).
The problem is that there are many things to palliate in these patients, he said, including obstruction, atelectasis, dyspnea, hemoptysis, and cough. Among the 211 patients in the two trials, the majority in both the Nd:YAG and PDT groups had dyspnea and cough, and 60% of both groups had hemoptysis. Similarly, 60% of patients in both groups had atelectasis and 90%, endobronchial obstruction, Dr. Pass said.
Patients randomized to PDT were administered porfimer sodium (2 mg/kg intravenously), followed 48 hours later by light activation at 630 nm. Objective tumor responses were evaluated by bronchoscopy 1 week and 1, 2, 3, and 6 months after therapy. Symptom palliation was assessed at the same intervals.
Objective tumor responses, Dr. Pass reported, were very similar between the PDT and Nd:YAG groups at 1 week (58% Nd:YAG, 59% PDT). Evaluation at 1 month, however, showed a 59% decline (to 30%) in response for patients in the Nd:YAG group, but no corresponding decline in the PDT group (55%). It is probably related to the actual oncologic effect that this therapy has, Dr. Pass commented. Its not just desiccation of the tumor, but a targeted tumor effect.
PDT therapy was also associated with a greater and longer-lasting effect on the resolution of atelec-tasis. Fully half of patients who had a luminal response went on to have a resolution of their atelec-tasis, Dr. Pass said.
Overall analysis of palliation of symptoms of dyspnea, cough, and hemoptysis showed PDT and Nd:YAG to be very similar, with improvements in specific symptoms in 90% of cases for both treatments. However, improvements in dyspnea favored PDT (20% vs 7%), Dr. Pass said, and a higher proportion of PDT group patients had a two-grade improvement in dyspnea (on a six-point scale).
In addition, at 1 month, control of hemoptysis in the PDT group was more than double the efficacy for the Nd:YAG group (71% vs 32%), and improvement in cough was greater (13% vs 5%).
If you compare any symptom improvement in the two groups at 1 month or at any time, you find that PDT was better than Nd:YAG (71% vs 64%), Dr. Pass said. Also, the treatment response was at least as good and probably better with PDT.
Data from these trials also showed similar adverse events (73% for PDT vs 64% for Nd:YAG) with equal numbers of withdrawals. The most frequent treatment-related adverse event for PDT was mild-to-moderate photosensitivity reaction, which occurred in 20% of patients. Also, both early and late life-threatening events such as respiratory insufficiency and fatal massive hemoptysis were similar between the two groups.
Caution With Tight Airways
Dr. Pass mentioned that in patients with a tight airway, early transient edematous responses are possible with PDT. Youve got to be careful about thatbut it did not lead to patients going on to more adverse events or fatal complications, he said.
He reported that there were no differences between the two groups in treatment-related early or late deaths, or in overall survival. There was a trend toward longer survival with PDT, which meant that patients receiving PDT were followed longer and underwent more bronchoscopies, which may have contributed to some late adverse events.
Photofrin has been approved for treatment of microinvasive NSCLC since 1998 and for palliation of obstructive esophageal cancer since 1995. The Oncology Drugs Advisory Committee has recommended that the FDA approve its use as palliation in late-stage NSCLC.