Investigational New Drugs

, Volume 20, Issue 3, pp 343–349

A Phase I Study of SPI-077 (Stealth® Liposomal Cisplatin) Concurrent with Radiation Therapy for Locally Advanced Head and Neck Cancer

  • David I. Rosenthal
  • Sue S. Yom
  • Li Liu
  • Mitchell Machtay
  • Kenneth Algazy
  • Randal S. Weber
  • Gregory S. Weinstein
  • Ara A. Chalian
  • Linda K. Miller
  • Kenneth RockwellJr
  • Margaret Tonda
  • Edward Schnipper
  • Diane Hershock
Article

DOI: 10.1023/A:1016201732368

Cite this article as:
Rosenthal, D.I., Yom, S.S., Liu, L. et al. Invest New Drugs (2002) 20: 343. doi:10.1023/A:1016201732368

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® 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/m2 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.

chemoradiationhead and neck cancertoxicity

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • 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 RockwellJr
    • 5
  • Margaret Tonda
    • 6
  • Edward Schnipper
    • 6
  • Diane Hershock
    • 3
  1. 1.Department of Radiation Oncology, Head and Neck SurgeryHospital of the University of PennsylvaniaUSA
  2. 2.University of Pennsylvania School of MedicineUSA
  3. 3.Department of Medicine, Hematology/Oncology Division, Head and Neck SurgeryHospital of the University of PennsylvaniaUSA
  4. 4.Department of Otorhinolaryngology, Head and Neck SurgeryHospital of the University of PennsylvaniaUSA
  5. 5.Investigational Drug ServiceUniversity of Pennsylvania Health SystemPhiladelphiaUSA
  6. 6.ALZA CorporationMountain ViewUSA