For advanced gastric cancer, diagnosis of peritoneal dissemination is mandatory prior to the decision of therapy; therefore, staging laparoscopy (SL) has gained wider clinical acceptance. We have reported the efficacy of SL with photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA). In this study, the safety and effectiveness of oral administration of 5-ALA PDD compared with that of conventional white-light laparoscopic diagnosis is assessed in a phase I/II study. This research also used a randomised double-blind comparison to explore the optimum dose of 5-ALA to be followed by a confirmatory study.
Subjects were patients with type 3 or 4 gastric cancer. A total of 20 or 40 mg/kg 5-ALA was administered orally 180–300 minutes before SL. The primary endpoint was safety; the secondary endpoints were sensitivity, specificity, positive predictive value, negative predictive value, and the proportion of patients with peritoneal dissemination.
Thirty-one patients, comprising 19 men and 12 women, were enrolled. Fourteen patients were allocated to the 20 mg/kg group and 17 to the 40 mg/kg group. The median age was 70 years. The proportions of adverse events were 53.8% and 41.2% in the 20 and 40 mg/kg groups, respectively. Hypotension was noted as serious adverse event in 1 patient. The sensitivities of PDD in the 20 and 40 mg/kg groups were higher (95.7% and 100%, respectively) than those of conventional diagnosis (73.9% and 67.8%) (p = 0.0625 and p = 0.0313). In terms of precision, the evaluation values of diagnosis through conventional imaging compared with PDD were as follows: sensitivity, 83.5% vs. 98.6%; specificity, 75.5% vs. 38.8%; positive predictive value, 82.2% vs. 69.6%; and negative predictive value, 75.5% vs. 95.0%, respectively. In addition, one more patient was found positive for dissemination via PDD.
This investigator-initiated clinical trial confirmed the safety and effectiveness of 5-ALA administration in PDD for peritoneal metastases in gastric cancer. Results indicated that both doses of 5-ALA may be clinically applicable. Thus, we are now conducting a confirmatory study to apply for pharmaceutical approval of 5-ALA.
Clinical trial identification
Legal entity responsible for the study
Prof. Yuichiro Doki
This work was supported by the clinical trial promotion pro-gram subsidized by the Japan Medical Association with theMinistry of Health, Labour and Welfare Research Grant
All authors have declared no conflicts of interest.