부산대학교 도서관

Byline: David I. Rosenthal (1), Sue S. Yom (2), Li Liu (1), Mitchell Machtay (1), Kenneth Algazy (3), Randal S. Weber (4), Gregory S. Weinstein (4), Ara A. Chalian (4), Linda K. Miller (1), Kenneth Rockwell (5), Margaret Tonda (6), Edward Schnipper (6), Diane Hershock (3) Keywords: chemoradiation; head and neck cancer; toxicity Abstract: Background: Liposomal cisplatinpreparations have two potential advantagesover the free drug when combined withradiation therapy (RT): 1) selective tumorlocalization, improving the therapeuticratio, and 2) prolonged half-life, allowingmore radiosensitization. We performed aPhase I study of Stealth(r) liposomalcisplatin (SPI-077) concurrent with RT forhead and neck squamous cell carcinoma(HNSCC). Methods: Patients with StageIVa/b HNSCC were treated with SPI-077,given intravenously twice two weeks apart,concurrent with RT (60--72 Gy in 6--7 weeks).The SPI-077 dose was escalated in standardphase I design. Results: Twenty patientsreceived 38 doses of SPI-077, escalatedfrom 20--200 mg/m.sup.2 in six dose levels.Two of these patients received one dosebecause of reversible Grade 3 livertoxicity or rash. Three patients had aGrade 1, and one had a Grade 2 infusionreaction. Four patients had transientlyelevated transaminases: Grade 1 (n = 1),Grade 2 (n = 1), and Grade 3 (n = 2). Grade 3neutropenia occurred in one patient. Therewas no ototoxicity, neurotoxicity, ornephrotoxicity. In-field radiation skin andmucosal toxicities did not appear to beintensified. Ten of 17 patients (59%)finishing treatment achieved initialcomplete response. Conclusions: Systemic andin-field radiation toxicities of SPI-077were minimal. Infusion reactions wereminimized with a slower and more diluteinitial infusion. Further dose escalationwas stopped in the absence of dose-limitingtoxicity to address the reformulation ofthe liposomally bound cisplatin.Nonetheless, this study shows that highdoses of SPI-077 can be given safely. Thepotentially beneficial therapeutic ratiosuggests that liposomal radiosensitizerpreparations warrant furtherinvestigation. Author Affiliation: (1) Department of Radiation Oncology, Head and Neck Surgery, Hospital of the University of Pennsylvania, USA (2) University of Pennsylvania School of Medicine, USA (3) Department of Medicine, Hematology/Oncology Division, Head and Neck Surgery, Hospital of the University of Pennsylvania, USA (4) Department of Otorhinolaryngology, Head and Neck Surgery, Hospital of the University of Pennsylvania, USA (5) Investigational Drug Service, University of Pennsylvania Health System, Philadelphia, PA, USA (6) ALZA Corporation, Mountain View, CA, USA Article History: Registration Date: 10/10/2004