PDT Improves QOL in Lung Cancer Patients Who Have Endobronchial Obstruction

LOUISVILLE, Kentucky--Photodynamic therapy (PDT) offers a simple and effective alternative to conventional techniques for palliative debridement of endobronchial obstructions in lung cancer patients, data from two clinical trials suggest.

Compared to YAG laser treatment, PDT with porfimer sodium (Photofrin) demonstrated better efficacy for relief of obstructions and improvement in dyspnea and cough. Aside from photosensitivity reactions, systemic adverse effects of the two treatments were similar.

"A large proportion of patients with advanced lung cancer have symptoms of dyspnea, coughing, and hemoptysis, which has a major effect on quality of life," said

Thomas J. Wieman, MD, an oncologist at the University of Louisville, Kentucky. "Many times, if the symptoms can be alleviated, the patients can lead fairly independent lives, at least for the 6 or 9 or 12 months they have remaining."

In his poster presentation at the ASCO meeting, Dr. Wieman reviewed data from two randomized comparisons of Photofrin and the Nd:YAG laser in patients who had endobronchial obstruction related to advanced lung cancer. For statistical analysis, he and his colleagues combined data from the two trials, which involved a total of 198 treated patients.

Photofrin is a photosensitizer that produces a local, selective cytotoxic reaction when activated by red nonthermal laser light, Dr. Wieman said. Previous studies have demonstrated efficacy of the treatment in obstructive esophageal cancer (Gastrointest Endosc 42:507-512, 1995).

Photodynamic therapy with Photofrin comprises a two-step process: (1) The photosensitizer is injected intravenously and selectively retained by tumor tissue. (2) Two days later, a 630 nm wavelength nonthermal red light is directed at the tumor, activating the retained photosensitizing agent.

Generation of free radicals leads to a selective, direct cytotoxic effect on the tumor. Necrotic tissue is debrided 2 days after light exposure to prevent obstruction and associated severe dyspnea.

In the trials, a second light exposure was optional at the treating physician’s discretion.

Treatment with the Nd:YAG laser consisted of unlimited energy applications until all accessible tumor was ablated.

A complete response was defined as total ablation of all endoscopically viable tumor; a partial response was an increase of at least 50% in the smallest luminal diameter. In this analysis, complete and partial responses were combined into an overall response rate.

Results of the two trials showed response rates of approximately 60% for both therapies at the end of 1 week. At 1 month, significantly more patients treated with photodynamic therapy maintained their responses, 55% vs 29% of patients treated with the laser.

Symptom Palliation

Also at 1 month, symptom palliation favored PDT for all symptoms assessed (dyspnea, cough, hemoptysis, sputum, and percent of patients with a clinically important benefit from therapy). Significantly more patients treated with Photofrin had improvement in dyspnea and cough, 30% and 27%, respectively, vs 17% and 13%, respectively, for laser treatment.

Systemic toxicity was similar for the two treatments with the exception of photosensitivity reaction, which occurred in 20% of Photofrin patients and none of the laser-treated patients. The incidence of fever and pain did not differ between the two groups. Pulmonary adverse effects were significantly more common with PDT, especially dyspnea (32% vs 17%) and bronchitis (11% vs 3%).

Neither treatment was associated with improved survival. Median survival was 166 days in patients treated with PDT and 157 days in the laser-treated group.

"PDT is simpler to perform and leads to a better functional result, at least over the short term," Dr. Wieman said. "It’s hard to measure long-term effects because the patients have so many systemic problems and a brief life expectancy."