Phase II study of direct intralesional gene transfer of Allovectin-7, an HLA-B7/β2-microglobulin DNA-liposome complex, in patients with metastatic melanoma

Alison T Stopeck, A. Jones, Evan M Hersh, J. A. Thompson, D. M. Finucane, J. C. Gutheil, R. Gonzalez

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Cutaneous melanoma is one of the most rapidly increasing cancers in the United States. Because of the lack of effective treatment options and toxicities of most chemotherapeutic and radiation regimes, immunotherapies such as vaccination therapy represent an attractive approach for patients with advanced melanoma. The purpose of this study was to evaluate the response rate, time to progression, and survival of patients with metastatic melanoma treated by direct intratumoral injection with Allovectin-7 (a plasmid DNA encoding the genes HLA-B7 and β2-microglobulin complexed with a cationic lipid mixture, DMRIE/DOPE. Fifty-two patients with metastatic melanoma were enrolled in this Phase II study. Therapy consisted of six intratumoral injections of 10 μg of Allovectin-7 over a 9-week period. Treatment was well tolerated. Treatment-related adverse events were mild to moderate, the most frequent of which were ecchymosis, pruritus (and/or discomfort at the injection site), and pneumothoraces. Regression of the injected lesion was observed in 18% of patients, including one complete response, three partial responses, and five minor responses. An overall response rate of 4% (two partial responses) was documented, and nine patients (18%) maintained stable disease for at least 11 weeks. Six patients remained alive 25.1 to 39.4 months from their first injection, including two patients with local (injected tumor) responses and one patient with an overall disease partial response. This study demonstrates that intratumoral administration of Allovectin-7 in metastatic melanoma is safe and can produce both responses in injected lesions and in overall disease. Clinical trials optimizing patient selection and combining Allovectin-7 with other modalities of therapy are currently ongoing in an effort to improve response rates.

Original languageEnglish (US)
Pages (from-to)2285-2291
Number of pages7
JournalClinical Cancer Research
Volume7
Issue number8
StatePublished - 2001

Fingerprint

HLA-B7 Antigen
Liposomes
Melanoma
DNA
Genes
Injections
Therapeutics
Ecchymosis
Allovectin-7
Pneumothorax
Pruritus
Immunotherapy
Patient Selection
Neoplasms
Vaccination
Plasmids
Clinical Trials
Radiation
Lipids
Skin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase II study of direct intralesional gene transfer of Allovectin-7, an HLA-B7/β2-microglobulin DNA-liposome complex, in patients with metastatic melanoma. / Stopeck, Alison T; Jones, A.; Hersh, Evan M; Thompson, J. A.; Finucane, D. M.; Gutheil, J. C.; Gonzalez, R.

In: Clinical Cancer Research, Vol. 7, No. 8, 2001, p. 2285-2291.

Research output: Contribution to journalArticle

@article{5d974baa163f4fc1baac5333bee5c70c,
title = "Phase II study of direct intralesional gene transfer of Allovectin-7, an HLA-B7/β2-microglobulin DNA-liposome complex, in patients with metastatic melanoma",
abstract = "Cutaneous melanoma is one of the most rapidly increasing cancers in the United States. Because of the lack of effective treatment options and toxicities of most chemotherapeutic and radiation regimes, immunotherapies such as vaccination therapy represent an attractive approach for patients with advanced melanoma. The purpose of this study was to evaluate the response rate, time to progression, and survival of patients with metastatic melanoma treated by direct intratumoral injection with Allovectin-7 (a plasmid DNA encoding the genes HLA-B7 and β2-microglobulin complexed with a cationic lipid mixture, DMRIE/DOPE. Fifty-two patients with metastatic melanoma were enrolled in this Phase II study. Therapy consisted of six intratumoral injections of 10 μg of Allovectin-7 over a 9-week period. Treatment was well tolerated. Treatment-related adverse events were mild to moderate, the most frequent of which were ecchymosis, pruritus (and/or discomfort at the injection site), and pneumothoraces. Regression of the injected lesion was observed in 18{\%} of patients, including one complete response, three partial responses, and five minor responses. An overall response rate of 4{\%} (two partial responses) was documented, and nine patients (18{\%}) maintained stable disease for at least 11 weeks. Six patients remained alive 25.1 to 39.4 months from their first injection, including two patients with local (injected tumor) responses and one patient with an overall disease partial response. This study demonstrates that intratumoral administration of Allovectin-7 in metastatic melanoma is safe and can produce both responses in injected lesions and in overall disease. Clinical trials optimizing patient selection and combining Allovectin-7 with other modalities of therapy are currently ongoing in an effort to improve response rates.",
author = "Stopeck, {Alison T} and A. Jones and Hersh, {Evan M} and Thompson, {J. A.} and Finucane, {D. M.} and Gutheil, {J. C.} and R. Gonzalez",
year = "2001",
language = "English (US)",
volume = "7",
pages = "2285--2291",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "8",

}

TY - JOUR

T1 - Phase II study of direct intralesional gene transfer of Allovectin-7, an HLA-B7/β2-microglobulin DNA-liposome complex, in patients with metastatic melanoma

AU - Stopeck, Alison T

AU - Jones, A.

AU - Hersh, Evan M

AU - Thompson, J. A.

AU - Finucane, D. M.

AU - Gutheil, J. C.

AU - Gonzalez, R.

PY - 2001

Y1 - 2001

N2 - Cutaneous melanoma is one of the most rapidly increasing cancers in the United States. Because of the lack of effective treatment options and toxicities of most chemotherapeutic and radiation regimes, immunotherapies such as vaccination therapy represent an attractive approach for patients with advanced melanoma. The purpose of this study was to evaluate the response rate, time to progression, and survival of patients with metastatic melanoma treated by direct intratumoral injection with Allovectin-7 (a plasmid DNA encoding the genes HLA-B7 and β2-microglobulin complexed with a cationic lipid mixture, DMRIE/DOPE. Fifty-two patients with metastatic melanoma were enrolled in this Phase II study. Therapy consisted of six intratumoral injections of 10 μg of Allovectin-7 over a 9-week period. Treatment was well tolerated. Treatment-related adverse events were mild to moderate, the most frequent of which were ecchymosis, pruritus (and/or discomfort at the injection site), and pneumothoraces. Regression of the injected lesion was observed in 18% of patients, including one complete response, three partial responses, and five minor responses. An overall response rate of 4% (two partial responses) was documented, and nine patients (18%) maintained stable disease for at least 11 weeks. Six patients remained alive 25.1 to 39.4 months from their first injection, including two patients with local (injected tumor) responses and one patient with an overall disease partial response. This study demonstrates that intratumoral administration of Allovectin-7 in metastatic melanoma is safe and can produce both responses in injected lesions and in overall disease. Clinical trials optimizing patient selection and combining Allovectin-7 with other modalities of therapy are currently ongoing in an effort to improve response rates.

AB - Cutaneous melanoma is one of the most rapidly increasing cancers in the United States. Because of the lack of effective treatment options and toxicities of most chemotherapeutic and radiation regimes, immunotherapies such as vaccination therapy represent an attractive approach for patients with advanced melanoma. The purpose of this study was to evaluate the response rate, time to progression, and survival of patients with metastatic melanoma treated by direct intratumoral injection with Allovectin-7 (a plasmid DNA encoding the genes HLA-B7 and β2-microglobulin complexed with a cationic lipid mixture, DMRIE/DOPE. Fifty-two patients with metastatic melanoma were enrolled in this Phase II study. Therapy consisted of six intratumoral injections of 10 μg of Allovectin-7 over a 9-week period. Treatment was well tolerated. Treatment-related adverse events were mild to moderate, the most frequent of which were ecchymosis, pruritus (and/or discomfort at the injection site), and pneumothoraces. Regression of the injected lesion was observed in 18% of patients, including one complete response, three partial responses, and five minor responses. An overall response rate of 4% (two partial responses) was documented, and nine patients (18%) maintained stable disease for at least 11 weeks. Six patients remained alive 25.1 to 39.4 months from their first injection, including two patients with local (injected tumor) responses and one patient with an overall disease partial response. This study demonstrates that intratumoral administration of Allovectin-7 in metastatic melanoma is safe and can produce both responses in injected lesions and in overall disease. Clinical trials optimizing patient selection and combining Allovectin-7 with other modalities of therapy are currently ongoing in an effort to improve response rates.

UR - http://www.scopus.com/inward/record.url?scp=0034885426&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034885426&partnerID=8YFLogxK

M3 - Article

C2 - 11489803

AN - SCOPUS:0034885426

VL - 7

SP - 2285

EP - 2291

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 8

ER -