PMID- 24097815 OWN - NLM STAT- MEDLINE DCOM- 20141016 LR - 20220408 IS - 1600-0455 (Electronic) IS - 0284-1851 (Linking) VI - 55 IP - 7 DP - 2014 Sep TI - Negative-balance isolated pelvic perfusion in patients with incurable symptomatic rectal cancer: results and drug dose correlation to adverse events. PG - 793-801 LID - 10.1177/0284185113507253 [doi] AB - BACKGROUND: Drug leakage and lack of a drug-removal system have prevented clinical application of isolated pelvic perfusion (IPP). These barriers were overcome with negative-balance IPP (NIPP) in experimental pig models. Here, a phase 1 clinical study of NIPP was performed in patients with incurable symptomatic rectal cancer. PURPOSE: To establish a safe regimen of high-dose regional chemotherapy with NIPP using cisplatin in patients with incurable rectal cancer. MATERIAL AND METHODS: Between June 2004 and January 2007, NIPP therapy was performed for 23 patients (11 women, 12 men; mean age, 58 years). NIPP was routinely performed twice over a 4-week interval. Dose-limiting toxicities (DLTs) were defined using a 5 + 3 design, and cisplatin doses were escalated from 170 mg/m(2), with a fixed 5-fluorouracil dose of 1000 mg/m(2). The grade of adverse events (AEs) at the first and second sessions of NIPP therapy, pharmacokinetics, and antitumor response were evaluated. RESULTS: No DLTs were observed during the first session of NIPP. However, at the second session, two patients experienced the DLT of neuropathy after administration of 200 mg/m(2) cisplatin. Therefore, 190 mg/m(2) cisplatin was indicated as the maximum tolerated dose (MTD). The plasma pelvic-to-systemic exposure ratio was 18.4 based on the maximum concentration and 19.0 based on the concentration-time curve. Solid tumor responses included complete response in two patients, partial response in five patients, stable disease in 15 patients, and progressive disease in one patient. CONCLUSION: NIPP may offer the safe delivery of high-dose regional chemotherapy (MTD of 190 mg/m(2) cisplatin) with negligible AEs and effective control of tumor growth in patients with incurable rectal cancer. CI - (c) The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav. FAU - Murata, Satoru AU - Murata S AD - Department of Radiology/Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan genji@nms.ac.jp. FAU - Onozawa, Shiro AU - Onozawa S AD - Department of Radiology/Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan. FAU - Kim, Chol AU - Kim C AD - Department of Anesthesiology, Nippon Medical School, Tokyo, Japan. FAU - Tajima, Hiroyuki AU - Tajima H AD - Department of Radiology/Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan. FAU - Kimata, Ryoji AU - Kimata R AD - Department of Urology, Nippon Medical School, Tokyo, Japan. FAU - Uchida, Eiji AU - Uchida E AD - Department of 1st Surgery, Nippon Medical School, Tokyo, Japan. FAU - Kumita, Shin-Ichiro AU - Kumita S AD - Department of Radiology/Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan. LA - eng PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131005 PL - England TA - Acta Radiol JT - Acta radiologica (Stockholm, Sweden : 1987) JID - 8706123 RN - 0 (Antineoplastic Agents) RN - Q20Q21Q62J (Cisplatin) RN - U3P01618RT (Fluorouracil) SB - IM MH - Adult MH - Aged MH - Antineoplastic Agents/administration & dosage/adverse effects MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/*adverse effects MH - Chemotherapy, Cancer, Regional Perfusion/instrumentation/*methods MH - Chronic Disease MH - Cisplatin/administration & dosage/adverse effects MH - Dose-Response Relationship, Drug MH - Extravasation of Diagnostic and Therapeutic Materials/diagnosis/*etiology/*prevention & control MH - Female MH - Fluorouracil/administration & dosage/adverse effects MH - Humans MH - Infusion Pumps MH - Male MH - Maximum Tolerated Dose MH - Middle Aged MH - Peripheral Nervous System Diseases/*chemically induced/diagnosis/prevention & control MH - Rectal Neoplasms/complications/diagnosis/*drug therapy MH - Survival Rate MH - Treatment Failure OTO - NOTNLM OT - Intervention OT - pelvis OT - rectum OT - treatment effects EDAT- 2013/10/08 06:00 MHDA- 2014/10/17 06:00 CRDT- 2013/10/08 06:00 PHST- 2013/10/08 06:00 [entrez] PHST- 2013/10/08 06:00 [pubmed] PHST- 2014/10/17 06:00 [medline] AID - 0284185113507253 [pii] AID - 10.1177/0284185113507253 [doi] PST - ppublish SO - Acta Radiol. 2014 Sep;55(7):793-801. doi: 10.1177/0284185113507253. Epub 2013 Oct 5.