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
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.
Its 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. Youve got to be careful
about thatbut it did not lead to patients going on to more
adverse events or fatal complications, he said.
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