J Gynecol Oncol.  2019 Jul;30(4):e59. 10.3802/jgo.2019.30.e59.

Pharmacokinetics of cisplatin during open and minimally-invasive secondary cytoreductive surgery plus HIPEC in women with platinum-sensitive recurrent ovarian cancer: a prospective study

• Petrillo M
• Zucchetti
• Cianci S
• Morosi L
• Ronsini C
• Colombo A
• D'Incalci
• Scambia G
• Fagotti A

• KMID: 2450238
• DOI: http://doi.org/10.3802/jgo.2019.30.e59

Abstract

OBJECTIVE
Evidences from animal models seem to suggest that minimally invasive surgery may enhance cisplatin diffusion when the drug is administered in the context of post-operative hyperthermic intraperitoneal chemotherapy (HIPEC). The present study evaluates the cisplatin pharmacokinetic profile in a prospective series of women with platinum sensitive recurrent epithelial ovarian cancer treated with open secondary cytoreductive surgery (O-SCS) or minimally-invasive secondary cytoreductive surgery (MI-SCS).
METHODS
Cisplatin levels were assessed at 0, 20, 40, 60, and 120 minutes in: 1) blood samples, 2) peritoneal perfusate, and 3) peritoneal biopsies at the end of HIPEC. Median Cmax has been used to identify women with high and low drug levels. Progression-free survival (PFS) was calculated as the time elapsed between SCS+HIPEC and secondary recurrence or last follow-up visit.
RESULTS
Nine (45.0%) women received MI-SCS, and 11 (55.0%) O-SCS. At 60 minutes, median cisplatin Cmax in peritoneal tissue was higher in patients treated with MI-SCS compared to O-SCS (Cmax=8.262 µg/mL vs. Cmax=4.057 µg/mL). Furthermore, median cisplatin plasma Cmax was higher in patients treated with MI-SCS compared to O-SCS (Cmax=0.511 vs. Cmax=0.254 µg/mL; p-value=0.012) at 120 minutes. With a median follow-up time of 24 months, women with higher cisplatin peritoneal Cmax showed a longer PFS compared to women with low cisplatin peritoneal levels (2-years PFS=70% vs. 35%; p-value=0.054).
CONCLUSIONS
We demonstrate for the first time that minimally invasive route enhances cisplatin peritoneal tissue uptake during HIPEC, further evaluations are needed to confirm the correlation between peritoneal cisplatin levels after HIPEC and survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01539785

Keyword

Epithelial Ovarian Cancer; Cytoreduction Surgical Procedure; Injections, Intraperitoneal; Endoscopy

MeSH Terms

Biopsy
Cisplatin*
Cytoreduction Surgical Procedures
Diffusion
Disease-Free Survival
Drug Therapy
Endoscopy
Female
Follow-Up Studies
Humans
Injections, Intraperitoneal
Minimally Invasive Surgical Procedures
Models, Animal
Ovarian Neoplasms*
Pharmacokinetics*
Plasma
Platinum
Prospective Studies*
Recurrence
Cisplatin
Platinum