PSM
Jesse Demuytere, MD
PhD-fellow
Laboratory of experimental surgery
Melle, Oost-Vlaanderen, Belgium
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
No in vivo data from randomized controlled trials exist to investigate the potential impact of hyperthermia in cisplatin HIPEC on pharmacokinetics and survival. Here, we report secondary endpoints of the OvIP1 study (NCT02567253), a multicenter randomized trial investigating tumor tissue platinum penetration after normothermic (37°C) versus hyperthermic (41°C) chemoperfusion with cisplatin at 75 or 120 mg/m2 in stage III EOC.
Methods:
Patients were randomized to normo- or hyperthermic chemoperfusion of 90 minutes with either high or low dose cisplatin at the time of surgery. During and after perfusion, blood, perfusate and tissue samples were obtained.
Morbidity up to 30 days after surgery was calculated using the comprehensive complication index (CCI). Intact cisplatin levels were determined in perfusate and plasma samples using UHPLC-MS/MS, after which area under the curve (AUC) and half-life (T1/2) were computed.
Results:
A total of fifty-four patients were included. The highest dose was amended to 100 mg/m2 due to higher than expected renal toxicity at the 120 mg/m2 dose level.
The total cisplatin dose was similar in both temperature groups at both dose levels. Mean T1/2 in perfusate was significantly lowered by hyperthermia in the low dose group (39.3 min vs 33 min, P=0.041), and to a lesser extent in the high dose group (42.8 min vs 33.4 min, P=0.068). Systemic uptake of cisplatin was not significantly affected by hyperthermia: AUC in plasma was similar in both groups (P=0.19 and P=0.44). A mean AUC ratioperfusate/plasma of 9.6 was observed with no significant between-group differences.
Mean CCI (37°C: 37.1; 41°C: 28.5) was not affected by hyperthermia (P=0.20). Patients were followed up for two years post-surgery. In an intention-to-treat analysis, one-year survival of 90.9% and a two-year survival ratio of 75% were reached. During follow-up, 27 patients recurred or died, leading to a RFS of 13.45 months. Hyperthermia and dose level did not affect OS and RFS significantly.
Conclusions:
HIPEC with cisplatin is feasible and safe at dose levels not exceeding 100 mg/m2, and leads to a favorable pharmacokinetic profile, which can be further enhanced by hyperthermia.