Phase I feasibility and pharmacologic study of weekly intraperitoneal paclitaxel: a Gynecologic Oncology Group pilot Study.

Abstract

Paclitaxel can be delivered by the IP route on a weekly schedule with both an acceptable toxicity profile and a major pharmacokinetic advantage for cavity exposure. The recommended dose and schedule for phase II study of IP paclitaxel is 60 to 65 mg/m2 weekly.

Proceedings of a GOG workshop on intraperitoneal therapy for ovarian cancer

“…Thus, the large saline fluid volume used to administer intraperitoneal chemotherapy not only assures drug distribution throughout the intraperitoneal space, but also retards drug clearance to make a drug more available to intraperitoneal tumor deposits. Finally, as documented by Howell et al and Casper et al [4,5] with intraperitoneal cisplatin, and by Markman et al and Francis, et al [8,9] with intraperitoneal paclitaxel, large systemic plasma concentration • time products of intraperitoneal administered drugs can be achieved in the absence of relatively low peak plasma concentrations. As a result of the latter phenomenon, IP administered cisplatin is associated with considerably less tinnitus, hearing loss and neutropenia than the same doses administered intravenously [10].…”

“…• IP chemotherapy treats both intraperitoneal tumor bed and extraperitoneal tumor through systemic recirculation (1,4,5,8,9) • IP chemotherapy achieves dose intensification in the intraperitoneal space of 20-1,000 fold that achieved with "high-dose" intravenous chemotherapy regimens (4,5,8,9) • IP chemotherapy reaches intraperitoneal sites that may not be reached by the intravenous route, especially when up to 2 L of dialysate are administered…”

Feasibility of weekly intraperitoneal versus intravenous paclitaxel therapy delivered from the day of radical surgery for gastric cancer: a preliminary safety analysis of the INPACT study, a randomized controlled trial

“…From these findings taken together, bone marrow toxicity should not be taken lightly in patients who received intraperitoneal PTX therapy on the day of or shortly after radical gastrectomy. Abdominal pain was the dose-limiting adverse event in the phase I trial of weekly intraperitoneal PTX therapy for ovarian cancer patients [17], but was not particularly common when these patients were compared with patients with received intravenous PTX therapy. The small sample size is one of the weaknesses of this study.…”

“…Thus the PTX phase of the treatment was limited to 8 weeks in the current study so that evidence-based systemic chemotherapy could be offered to the participants thereafter. In addition, PTX is known to have limited capacity to directly penetrate into tumor tissue [17]. Therefore accrual of patients who are likely candidates for R0/R1 resection rather than R2 resection was encouraged.…”

“…In group A, patients received PTX intraperitoneally at 60 mg/ m 2 on the day of surgery (day 1) and on days 15, 22, 29, 43, 50, and 57. The dose of PTX administered intraperitoneally is based on a phase I trial performed in the USA for ovarian cancer patients [17]. PTX was dissolved in 1000 mL saline, and its delivery on the day of surgery was performed on closure of the abdomen through a catheter temporarily placed through the surgical incision.…”