A phase 1 study of granulocyte macrophage colony-stimulating factor (sargramostim) and escalating doses of thalidomide in patients with high-risk malignant melanoma

Jose Lutzky, Robert Weber, Yvonne Nunez, Matt Gillett, Lynn Spitler

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

This phase 1 study evaluated the safety and tolerability of adjuvant treatment with subcutaneous granulocyte macrophage colony-stimulating factor (GM-CSF) administered in combination with escalating doses of thalidomide in patients with surgically resected stage II (T4), III, or IV melanoma at high risk for recurrence. Adjuvant treatment included GM-CSF 125μg/m subcutaneously for 14 days and thalidomide at an initial dose of 50mg/d, escalated in cohorts of 3 to 6 patients each to a maximum of 400mg/d followed by 14 days of rest. Treatment was continued for up to 1 year in the absence of disease progression. Of 19 patients treated, the most common toxicities were grade 1/2 constipation (68%), fatigue (58%), neuropathy (42%), bone and joint pain (37%), and dyspnea, dizziness, injection site skin reaction, and somnolence (32% each). Thrombotic events in 3 of 19 patients (16%), including 1 treatment-related death, were the most serious adverse events and were thought to be due to thalidomide. With a median follow-up of 945 days (2.6y), 8 (42%) patients were alive, including 1 with disease and 7 without evidence of disease. GM-CSF plus thalidomide as adjuvant therapy for patients with resected high-risk melanoma was associated with a high incidence of thrombotic events. Because life-threatening events are unacceptable in the adjuvant setting, up-front antithrombotic prophylaxis will be necessary for further evaluation of GM-CSF plus thalidomide as a viable regimen in this patient group.

Original languageEnglish (US)
Pages (from-to)79-85
Number of pages7
JournalJournal of Immunotherapy
Volume32
Issue number1
DOIs
StatePublished - Jan 2009
Externally publishedYes

Keywords

  • Adjuvant
  • GM-CSF
  • Melanoma
  • Thalidomide
  • Thrombotic

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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