Photodynamic Therapy for Palliation of Locally Advanced Lung Cancer

In patients with endobronchial obstruction due to locally advanced lung cancer, photodynamic therapy (PDT) with porfimer sodium (Photofrin) affords as good and probably better palliation than therapy with a neodymium/yttrium-aluminum-garnet (Nd:YAG) laser, the standard treatment. This was the conclusion reached by two international prospective, randomized trials. Results of the trials were presented by Harvey I. Pass, MD, professor of surgery and oncology at Wayne State University, at a satellite symposium held in conjunction with the Society for Thoracic Surgeons annual meeting.

“The problem is that there are many symptoms to palliate in these patients,” said Dr. Pass. They include obstruction, atelectasis, dyspnea, hemoptysis, and cough. Among standard alternative treatments have been total parenteral nutrition (TPN) or the use of stents, although the latter may be subject to migration or associated with reflux and/or pain.

The American Cancer Society estimates that 171,500 patients were diagnosed with lung cancer in 1998. Of those, 20,000 to 25,000 patients may be candidates for treatment with porfimer sodium.

The majority of the 211 patients enrolled in both the Nd:YAG and PDT groups of the trials had dyspnea and cough, and 60% had hemoptysis. “Similarly, 60% of both groups had atelectasis and 90% had endobronchial obstruction,” said Dr. Pass.

Patients (N = 102) randomized to PDT were treated with porfimer sodium (2 mg/kg) intravenously, followed by light activation at 630 nm 48 hours later. Objective tumor responses were evaluated by bronchoscopy at 1 week and at 1, 2, 3, and 6 months after therapy. Symptom palliation was assessed at the same intervals.

Tumor Responses and Symptom Relief

Objective tumor responses, Dr. Pass reported, were very similar between the PDT and Nd:YAG groups at 1 week (59% vs 58%). However, an evaluation at 1 month revealed a 59% decline (to 30%) in the response of patients in the Nd:YAG group but no corresponding decline in the PDT group (55%). “It is probably related to the actual oncological effect that this therapy has,” said Dr. Pass. “It’s not just desiccation of the tumor, but a targeted tumor effect,” he added.

Photodynamic therapy also was associated with a greater and longer-lasting effect on the resolution of atelectasis. “Fully half of patients who had a luminal response went on to have a resolution of their atelectasis,” said Dr. Pass.

An 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 among 90% of patients in both groups. “However, improvements in dyspnea favored PDT (20% vs 7%),” said Dr. Pass, with a higher proportion of patients in the PDT group achieving a two-grade improvement in dyspnea. In addition, control of hemoptysis in the PDT group was more than double that in the Nd:YAG group (71% vs 32%) at 1 month, as was improvement in cough (13% vs 5%).

Adverse Events Also Similar

“If you looked at any symptom improvement in these patients and you compared them in the two groups at 1 month or at any time, what you found was that PDT was better than Nd:YAG (71% vs 64%),” said Dr. Pass. “Also, the treatment response was at least as good and probably better with PDT.”

Data from these trials, which contributed to the FDA approval of porfimer sodium, 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 a mild to moderate photosensitivity reaction, which occurred in 20% of patients. Also, rates of both early and late life-threatening events, such as respiratory insufficiency and fatal massive hemoptysis, were similar in the two groups.

In addition, where there is a tight airway, early transient edematous responses are possible with PDT. “You’ve got to be careful about that—but it did not lead to patients going on to more adverse events or fatal complications,” he said.

Summary

In summing up, Dr. Pass noted that about 74% of patients with endobronchial non-small-cell lung cancer will have a tumor response after PDT, 50% will have improvement in atelectasis, and a third will have marked (two-category) symptom improvement.

There were no differences between the two groups in treatment-related early or late deaths, or in overall survival. However, a trend toward longer survival also entailed more bronchoscopies for the PDT group, which may have contributed to increased adverse events.

Porfimer sodium has been indicated for the treatment of microinvasive non-small-cell lung cancer since January 1998 and for the palliation of obstructive esophageal cancer since December 1995.

Controlling the Side Effects of Porfimer Sodium

Following injection, porfimer sodium 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 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). Visible light stimulates photoactivation and therefore, ultraviolet sunscreens do not offer protection. Furthermore, 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. Outdoors, patients should wear sunglasses with an average light transmittance of less than 4%.