Читать книгу Intracranial Gliomas Part III - Innovative Treatment Modalities - Группа авторов - Страница 19

The reported results of PDT of malignant gliomas generally compare favorably with historical data, but there is a limited number of controlled studies. While the organization of a large scale double-blind randomized placebo-controlled trial for evaluation of PDT efficacy seems difficult and not very meaningful, carefully planned controlled phase III studies are definitely warranted [32]. To date three comparative studies have been conducted.

The first randomized controlled trial on PDT of malignant gliomas was done by Muller and Willson [6, 33]. It enrolled 43 patients who underwent resection of GBM followed by PDT with Photofrin^® (dose 2 mg/kg) and also a control group of 34 patients in whom tumor removal without PDT was done. Postoperative FRT was administered in all cases. Median survival was 11 months (95% CI 6–14 months) in the treatment group and 8 months (95% CI 3–10 months) in the control group. A 38% increase of median survival with PDT as well as greater 6-month survival rate in the treatment group were statistically significant, but Kaplan–Meier curves crossed over at 15 months [6, 33].

Kostron et al. [27] performed a non-randomized controlled phase II study on PDT with Foscan^® in 26 patients with recurrent GBM. Before treatment all tumors progressed and standard therapeutic options (irradiation, chemotherapy) were exhausted. Aggressive fluorescence-guided resection (macroscopically total in 75% of cases) was followed by intraoperative PDT. The median time-to-progression (TTP) after surgery was 6 months, median survival was 8.5 months, and 2-year survival rate was 15%. Comparison with matched controls revealed significantly better (p < 0.001) survival in the treatment group [27].

Finally, Eljamel et al. [29] conducted a single-center randomized controlled phase III trial on PDT with Photofrin^® after 5-ALA-induced fluorescence-guided resection of newly diagnosed GBM. In the study group (n = 13) the bulk of the tumor was removed and a balloon diffuser was implanted with subsequent repetitive PDT (5 sessions; 100 J/cm² each) during the postoperative period. In the control group (n = 14) the tumor was resected, but PDT was not done. After surgery all patients received standard FRT and were followed clinically and radiologically every 3 months until death. There was no statistical significant difference in the frequency of adjuvant and salvage treatments between the two cohorts. The mean survival of patients in the study and control groups was 52.8 weeks (95% CI 40–65 weeks) and 24.2 weeks (95% CI 18–30 weeks), respectively (p < 0.001). The mean KPS score at 6 months after surgery in the study and control groups was 80 and 70, respectively (p = 0.02). Although patients in the study group performed worse before surgery, their KPS scores improved to a much higher level postoperatively compared to controls (an absolute difference of 20 points). There was no residual tumor on discharge in 10 out of 13 patients in the study group and in 4 out of 14 patients in the control group. There was no difference between the groups in the average length of stay in the hospital or in complication rate. The mean TTP after treatment in the study and control groups was 8.6 and 4.8 months, respectively (p < 0.01) [29].

Although the sample sizes of these controlled studies were relatively small, they demonstrated a potential beneficial effect of PDT for prolongation of survival in patients with GBM in comparison to conventional treatment. However, according to the clinical data accumulated to date it is becoming evident that PDT cannot be equally effective in all cases of malignant gliomas, thus patient selection is very important to maximize its benefits. PDT should be strictly regarded as an adjuvant therapy. Extent of its therapeutic impact is limited to the depth of tissue penetration of the light, which varies from 2.5 to 5 mm depending on the wavelength, thus the corresponding effective distance of photo-irradiation is limited to 0.75–1.5 cm [7, 30]. Therefore aggressive resection of the tumor may be an important prerequisite for the clinical effectiveness of intraoperative PDT [31].