Regional Therapies
Megan M. Harper, MS, MD
Resident
University of Kentucky
Lexington, Kentucky, United States
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Agents for hyperthermic intraperitoneal chemotherapy (HIPEC) have remained unchanged for nearly a decade. Nano-liposomal irinotecan (nal-Iri) is a promising option for HIPEC administration given its systemic safety, delivery of higher pro-drug and active metabolite concentrations, large molecular weight, and heat stability. Here we report pharmacokinetic (PK) data of the first phase 1 trial of nal-Iri for HIPEC.
Methods:
Patients with peritoneal carcinomatosis from appendiceal and colorectal cancers were administered HIPEC nal-Iri for 30 min at 42°C at 70 (n=3), 140 (n=6), and 210 (n=3) mg/m2 during cytoreductive surgery (CRS). Venous blood samples were collected prior to and after HIPEC, and at time points 1, 3, 6, 24, 48, 72 h. Irinotecan, active metabolite SN38, and inactive secondary metabolite SN38G were measured at each time point for all samples. Data were analyzed using standard PK calculations and included maximum plasma concentration (Cmax, ng/mL), time to Cmax (TCmax, h), and total concentration over time or area-under-the-curve (AUC, h*ng/mL).
Results: We successfully obtained blood samples at every time point for all 12 patients enrolled in the study. We found that at all dose-dependent concentrations, peak and total-time concentrations (Cmax and AUC0-72h) for irinotecan, SN38, and SN38G were far below comparable IV nal-Iri concentrations (< 1/100th). Plasma irinotecan TCmax was 24h, approximately 10-fold slower than IV nal-Iri, for all dose-dependent concentrations. Table 1.
Conclusions: Our study reveals extremely low plasma irinotecan and SN38 concentrations following IP nal-Iri administration, up to 72 h post-HIPEC. This makes nal-Iri a promising novel HIPEC agent because concentrations stay elevated in the peritoneum to target residual tumor cells while demonstrating little systemic absorption. Clinical trial information: NCT04088786.