 |
Clinical studies of PDT with PHOTOFRIN were conducted in patients with obstructing esophageal and endobronchial nonsmall cell lung cancers and in patients with early-stage radiologically occult endobronchial cancer. In all clinical studies, the method of PDT administration was essentially identical. A course of therapy consisted of one injection of PHOTOFRIN (2mg/kg administered as a slow intravenous injection over 3-5 minutes) followed by up to two nonthermal applications of 630 nm laser light. Doses of 300 J/cm of tumor length were used in esophageal cancer. Doses of 200 J/cm were used in endobronchial cancer for both palliation of obstructing cancer and treatment of superficial lesions. The first application of light occurred 40-50 hours after injection. Debridement of residua was performed via endoscopy/bronchoscopy 96-120 hours after injection, after which any residual tumor could be retreated with a second laser light application at the same dose for the initial treatment. Additional courses of PDT with PHOTOFRIN were allowed after 1 month, up to a maximum of three courses.
PDT with PHOTOFRIN was utilized in a multicenter, single-arm study in 17 patients with completely obstructing esophageal carcinoma. Assessments were made at 1 week and 1 month after the last treatment procedure. As shown in Table 1, after a single course of therapy, 94% of patients obtained an objective tumor response and 76% of patients experienced some palliation of their dysphagia. On average, before treatment these patients had difficulty swallowing liquids, even saliva. After one course of therapy, there was a statistically significant improvement in mean dysphagia grade (1.5 units, p <0.05) and 13 of 17 patients could swallow liquids without difficulty 1 week and/or 1 month after treatment. Based on all courses, three patients achieved a complete tumor response (CR). In two of these patients, the CR was documented only at Week 1 as they had no further assessments. The third patient achieved a CR after a second course of therapy, which was supported by negative histopathology and maintained for the entire follow-up of 6 months.
Of the 17 treated patients, 11 (65%) received clinically important benefit from PDT. Clinically important benefit was defined hierarchically as a complete tumor response (3 patients), achievement of normal swallowing (2 patients went from Grade 5 dysphagia to Grade1), or achievement of a marked improvement of two or more grades of dysphagia with minimal adverse reactions (6 patients). Duration of benefit was calculated only for the period with documented evidence of improvement. All of these patients were still in response at their last assessment and, therefore, the estimate of 69 days is conservative. The median survival for these patients was 115 days.
| TABLE 1. Course 1 Efficacy Results in Patients with Completely Obstructing Esophageal Cancer. | |
| EFFICACY PARAMETER | PDT n=17 |
| OBJECTIVE TUMOR RESPONSE (a) | |
| Week 1 | 82% |
| Month 1 | 35% (b) |
| Any Assessment (c) | 94% |
| IMPROVEMENT IN DYSPHAGIA (d) | |
| Week1 | 71% |
| Month 1 | 47% |
| Any Assessment (c) | 76% |
| MEAN DYSPHAGIA GRADE AT BASELINE (e) | 4.6 |
| MEAN IMPROVEMENT IN DYSPAGIA GRADE | |
| Week 1 | 1.4 |
| Month 1 | 1.5 |
| MEAN NUMBER OF LASER APPLICATIONS | 1.4 |
(a) CR + PR, CR = complete response(absence of endoscopically visible tumor), PR = partial response (appearance of a visible lumen)
(b) Eight of the 17 treated patients did not have assessments at Month 1.
(c) Week 1 or Month 1
(d) Patients with at least a one-grade improvement in dysphagia grade
(e) Dysphagia Scale: Grade 1 = normal swallowing, Grade 2 = difficulty swallowing some hard solids; can swallow semisolids, Grade 3 = unable to swallow any solids; can swallow liquids, Grade 4 = difficulty swallowing liquids, Grade 5 = unable to swallow saliva
Comments to: KKee@partners.org
©2007, Division of Thoracic Surgery at Brigham and Women's Hospital. All rights reserved.
Division of Thoracic Surgery
Brigham and Women's Hospital
75 Francis Street
Boston, MA 02115
Phone: (617) 732-6824