A possible association between aprotinin and improved survival after radical surgery for mesothelioma

Abstract

Background: Aprotinin has been used to decrease blood loss with complicated cardiac surgery but has not been investigated in extrapleural pneumonectomy, an operation that does not use cardiopulmonary bypass. In this prospective, randomized, placebo-controlled, double-blind trial, the authors investigated whether aprotinin decreased blood loss in patients who underwent this operation.

Methods: After appropriate statistical design and institutional review board approval, eligible patients who were scheduled for extrapleural pneumonectomy were randomized to receive either aprotinin or placebo during the operation. Blood loss and survival data were obtained from electronic medical records and surgical databases.

Results: Of 20 patients who were enrolled, 16 patients met criteria for blood loss analysis. Four patients were excluded from the blood loss analysis: Three patients were inoperable because of tumor spread and underwent limited surgery, and 1 patient died intraoperatively because of acute, massive hemorrhage. The mean blood loss was 769 mL with aprotinin versus 1832 mL with placebo (P = .05; Wilcoxon test). All 20 patients were included in survival analyses. All 9 patients who received placebo died. In contrast, 7 of 11 patients who received aprotinin remained alive at the time of the current report. Kaplan-Meier survival curves differed significantly between the 2 groups (P = .0004). A Bayesian multivariate survival analysis of 18 patients who had complete data available on 8 prognostic variables indicated a posterior probability of .99 that aprotinin was beneficial.

Conclusions: Aprotinin decreased blood loss. After accounting for covariate effects, there was a significant comparative benefit with aprotinin in postoperative survival. This finding was unexpected and could not be considered conclusive because of the small size of the current study. A confirmatory study may be warranted.

Figure 1

This box-and-whiskers plot depicts the median, interquartile range, and range for estimated blood loss in patients who received either aprotinin or placebo during extrapleural pneumonectomy (N = 16 patients).

Figure 2

Kaplan-Meier curves of survival probability for the aprotinin group (N = 11 patients, including 3 who were inoperable) and the placebo group (N = 9 patient, including 1 operative death). Survival length differed significantly (P = .0004; log-rank test) between the 2 treatment groups.

Figure 3

Kaplan-Meier curves of progression-free survival probability for the aprotinin group (N = 8 patients who were evaluable for disease progression) and the placebo group (N = 8 patients who were evaluable for disease progression). Progression-free survival did not differ significantly (P = .131; log-rank test) between the 2 treatment groups.