Phase 2 study of the g209-2M melanoma peptide vaccine and low-dose interleukin-2 in advanced melanoma: Cancer and Leukemia Group B 509901 Journal Article
| Authors: | Roberts, J. D.; Niedzwiecki, D.; Carson, W. E.; Chapman, P. B.; Gajewski, T. F.; Ernstoff, M. S.; Hodi, F. S.; Shea, C.; Leong, S. P.; Johnson, J.; Zhang, D.; Houghton, A.; Haluska, F. G. |
| Article Title: | Phase 2 study of the g209-2M melanoma peptide vaccine and low-dose interleukin-2 in advanced melanoma: Cancer and Leukemia Group B 509901 |
| Abstract: | High-dose interleukin-2 (IL-2) is the only approved immunologic therapy for advanced melanoma, but response rates are low and significant toxicities limit treatment to otherwise healthy patients. g209-2M is a nanopeptide engineered to mimic an epitope of the gp100 melanocyte differentiation protein that is recognized in a human leukocyte antigen (HLA)-restricted manner by melanoma tumor-infiltrating lymphocytes in some patients. Previous reports indicated that administration of the g209-2M peptide could induce g209-reactive circulating T cells in patients with melanoma and that the combination of g209-2M and high-dose IL-2 might be a more active treatment than high-dose IL-2 alone. Low-dose IL-2 is not active but has significant biologic effects, and because of a different toxicity profile, it can be offered to most patients. The primary objective of this cooperative group phase 2 study was to determine the activity of the combination of g209-2M and low-dose IL-2 in advanced melanoma. Twenty-six HLA appropriate patients with advanced melanoma received subcutaneous g209-2M peptide once every 3 weeks and subcutaneous IL-2 (5 million IU/m2) daily for 5 days during the first and second weeks. Patients were monitored for tumor response, toxicity, and induction of g209-reactive circulating T cells. There were no objective responses. There were no toxic deaths and no grade 4 toxicities. More than half of the patients experienced some grade 2 toxicity and one quarter experienced grade 3 toxicity. There was no convincing evidence by enzyme-linked immunospot or tetramer analysis of induction of g209-reactive circulating T cells. The combination of g209-2M and low-dose IL-2 is safe and tolerable but inactive against advanced melanoma. Absence of evidence of immunization raises concerns for peptide-based immunization strategies with concurrent IL-2. Copyright © 2005 by Lippincott Williams & Wilkins. |
| Keywords: | adult; clinical article; treatment outcome; aged; aged, 80 and over; middle aged; clinical trial; constipation; fatigue; advanced cancer; diarrhea; dose response; hypertension; antineoplastic agent; anorexia; t lymphocyte; interleukin 2; cancer immunotherapy; edema; low drug dose; melanoma; infection; phase 2 clinical trial; neoplasm recurrence, local; anemia; skin neoplasms; nausea; vomiting; antineoplastic combined chemotherapy protocols; myalgia; extrapyramidal symptom; drug effect; dose-response relationship, drug; abdominal pain; alanine aminotransferase blood level; arthralgia; aspartate aminotransferase blood level; chill; drug hypersensitivity; dyspnea; fever; hyperglycemia; injection site reaction; pruritus; rash; syncope; alanine aminotransferase; aspartate aminotransferase; allergic rhinitis; hypoalbuminemia; insomnia; skin tumor; immunology; rigor; thorax pain; mononuclear cell; leukocytes, mononuclear; gamma interferon; cancer vaccine; cancer vaccines; membrane glycoproteins; cardiovascular disease; tumor recurrence; peptide fragments; membrane protein; peptide fragment; cytokine production; headache; hot flush; heart arrhythmia; peptide vaccine; abnormally high substrate concentration in blood; enzyme linked immunospot assay; abdominal cramp; interleukin-2; dysgeusia; hyperhidrosis; phase ii trial; melanocyte lineage specific antigen gp100; melanocyte lineage-specific antigen gp100; melanoma vaccine; conjunctivitis |
| Journal Title: | Journal of Immunotherapy |
| Volume: | 29 |
| Issue: | 1 |
| ISSN: | 1524-9557 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2006-01-01 |
| Start Page: | 95 |
| End Page: | 101 |
| Language: | English |
| PUBMED: | 16365605 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 17" - "Export Date: 4 June 2012" - "CODEN: JOIME" - "Source: Scopus" |
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