Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma

Richard F. Little, Karen Aleman, Pallavi Kumar, Kathleen M. Wyvill, James M. Pluda, Elizabeth Read-Connole, Victoria Wang, Stefania Pittaluga, Andrew T. Catanzaro, Seth M. Steinberg, Robert Yarchoan

Research output: Contribution to journalArticle

Abstract

Thirty-six patients with AIDS-associated Kaposi sarcoma (KS) requiring chemotherapy were treated for six 3-week cycles of pegylated liposomal doxorubicin (20 mg/m2) plus interleukin-12 (IL-12; 300 ng/kg subcutaneously twice weekly), followed by 500 ng/kg subcutaneous IL-12 twice weekly for up to 3 years. All received highly active antiretroviral therapy (HAART). Twenty-two had poor-prognosis KS (T1S1). Thirty patients had a major response, including 9 with complete response, yielding an 83.3% major response rate (95% confidence interval: 67.2%-93.6%). Median time to first response was 2 cycles. Median progression was not reached at median potential follow-up of 46.9 months. Of 27 patients with residual disease when starting maintenance IL-12, 15 had a new major response compared with this new baseline. The regimen was overall well tolerated; principal toxicities were neutropenia, anemia, transaminitis, and neuropsychiatric toxicity. Patients had increases in serum IL-12, interferon gamma, and inducible protein-10 (IP-10), and these remained increased at weeks 18 and 34. The regimen of IL-12 plus liposomal doxorubicin yielded rapid tumor responses and a high response rate in patients with AIDS-KS receiving HAART, and responses were sustained on IL-12 maintenance therapy. A randomized trial of IL-12 in this setting may be warranted. This study is registered at http://www.clinicaltrials.gov as no. NCT00020449.

Original languageEnglish (US)
Pages (from-to)4165-4171
Number of pages7
JournalBlood
Volume110
Issue number13
DOIs
StatePublished - Dec 15 2007
Externally publishedYes

Fingerprint

Interleukin-12
Kaposi's Sarcoma
Highly Active Antiretroviral Therapy
Toxicity
Acquired Immunodeficiency Syndrome
Chemokine CXCL10
Interleukin-15
Chemotherapy
liposomal doxorubicin
AIDS-related Kaposi sarcoma
Neutropenia
Interferon-gamma
Anemia
Tumors
Maintenance
Confidence Intervals
Drug Therapy
Serum
Neoplasms

ASJC Scopus subject areas

  • Hematology

Cite this

Little, R. F., Aleman, K., Kumar, P., Wyvill, K. M., Pluda, J. M., Read-Connole, E., ... Yarchoan, R. (2007). Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma. Blood, 110(13), 4165-4171. https://doi.org/10.1182/blood-2007-06-097568

Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma. / Little, Richard F.; Aleman, Karen; Kumar, Pallavi; Wyvill, Kathleen M.; Pluda, James M.; Read-Connole, Elizabeth; Wang, Victoria; Pittaluga, Stefania; Catanzaro, Andrew T.; Steinberg, Seth M.; Yarchoan, Robert.

In: Blood, Vol. 110, No. 13, 15.12.2007, p. 4165-4171.

Research output: Contribution to journalArticle

Little, RF, Aleman, K, Kumar, P, Wyvill, KM, Pluda, JM, Read-Connole, E, Wang, V, Pittaluga, S, Catanzaro, AT, Steinberg, SM & Yarchoan, R 2007, 'Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma', Blood, vol. 110, no. 13, pp. 4165-4171. https://doi.org/10.1182/blood-2007-06-097568
Little, Richard F. ; Aleman, Karen ; Kumar, Pallavi ; Wyvill, Kathleen M. ; Pluda, James M. ; Read-Connole, Elizabeth ; Wang, Victoria ; Pittaluga, Stefania ; Catanzaro, Andrew T. ; Steinberg, Seth M. ; Yarchoan, Robert. / Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma. In: Blood. 2007 ; Vol. 110, No. 13. pp. 4165-4171.
@article{1dd81e0150d6449388374a988c8083c4,
title = "Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma",
abstract = "Thirty-six patients with AIDS-associated Kaposi sarcoma (KS) requiring chemotherapy were treated for six 3-week cycles of pegylated liposomal doxorubicin (20 mg/m2) plus interleukin-12 (IL-12; 300 ng/kg subcutaneously twice weekly), followed by 500 ng/kg subcutaneous IL-12 twice weekly for up to 3 years. All received highly active antiretroviral therapy (HAART). Twenty-two had poor-prognosis KS (T1S1). Thirty patients had a major response, including 9 with complete response, yielding an 83.3{\%} major response rate (95{\%} confidence interval: 67.2{\%}-93.6{\%}). Median time to first response was 2 cycles. Median progression was not reached at median potential follow-up of 46.9 months. Of 27 patients with residual disease when starting maintenance IL-12, 15 had a new major response compared with this new baseline. The regimen was overall well tolerated; principal toxicities were neutropenia, anemia, transaminitis, and neuropsychiatric toxicity. Patients had increases in serum IL-12, interferon gamma, and inducible protein-10 (IP-10), and these remained increased at weeks 18 and 34. The regimen of IL-12 plus liposomal doxorubicin yielded rapid tumor responses and a high response rate in patients with AIDS-KS receiving HAART, and responses were sustained on IL-12 maintenance therapy. A randomized trial of IL-12 in this setting may be warranted. This study is registered at http://www.clinicaltrials.gov as no. NCT00020449.",
author = "Little, {Richard F.} and Karen Aleman and Pallavi Kumar and Wyvill, {Kathleen M.} and Pluda, {James M.} and Elizabeth Read-Connole and Victoria Wang and Stefania Pittaluga and Catanzaro, {Andrew T.} and Steinberg, {Seth M.} and Robert Yarchoan",
year = "2007",
month = "12",
day = "15",
doi = "10.1182/blood-2007-06-097568",
language = "English (US)",
volume = "110",
pages = "4165--4171",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "13",

}

TY - JOUR

T1 - Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma

AU - Little, Richard F.

AU - Aleman, Karen

AU - Kumar, Pallavi

AU - Wyvill, Kathleen M.

AU - Pluda, James M.

AU - Read-Connole, Elizabeth

AU - Wang, Victoria

AU - Pittaluga, Stefania

AU - Catanzaro, Andrew T.

AU - Steinberg, Seth M.

AU - Yarchoan, Robert

PY - 2007/12/15

Y1 - 2007/12/15

N2 - Thirty-six patients with AIDS-associated Kaposi sarcoma (KS) requiring chemotherapy were treated for six 3-week cycles of pegylated liposomal doxorubicin (20 mg/m2) plus interleukin-12 (IL-12; 300 ng/kg subcutaneously twice weekly), followed by 500 ng/kg subcutaneous IL-12 twice weekly for up to 3 years. All received highly active antiretroviral therapy (HAART). Twenty-two had poor-prognosis KS (T1S1). Thirty patients had a major response, including 9 with complete response, yielding an 83.3% major response rate (95% confidence interval: 67.2%-93.6%). Median time to first response was 2 cycles. Median progression was not reached at median potential follow-up of 46.9 months. Of 27 patients with residual disease when starting maintenance IL-12, 15 had a new major response compared with this new baseline. The regimen was overall well tolerated; principal toxicities were neutropenia, anemia, transaminitis, and neuropsychiatric toxicity. Patients had increases in serum IL-12, interferon gamma, and inducible protein-10 (IP-10), and these remained increased at weeks 18 and 34. The regimen of IL-12 plus liposomal doxorubicin yielded rapid tumor responses and a high response rate in patients with AIDS-KS receiving HAART, and responses were sustained on IL-12 maintenance therapy. A randomized trial of IL-12 in this setting may be warranted. This study is registered at http://www.clinicaltrials.gov as no. NCT00020449.

AB - Thirty-six patients with AIDS-associated Kaposi sarcoma (KS) requiring chemotherapy were treated for six 3-week cycles of pegylated liposomal doxorubicin (20 mg/m2) plus interleukin-12 (IL-12; 300 ng/kg subcutaneously twice weekly), followed by 500 ng/kg subcutaneous IL-12 twice weekly for up to 3 years. All received highly active antiretroviral therapy (HAART). Twenty-two had poor-prognosis KS (T1S1). Thirty patients had a major response, including 9 with complete response, yielding an 83.3% major response rate (95% confidence interval: 67.2%-93.6%). Median time to first response was 2 cycles. Median progression was not reached at median potential follow-up of 46.9 months. Of 27 patients with residual disease when starting maintenance IL-12, 15 had a new major response compared with this new baseline. The regimen was overall well tolerated; principal toxicities were neutropenia, anemia, transaminitis, and neuropsychiatric toxicity. Patients had increases in serum IL-12, interferon gamma, and inducible protein-10 (IP-10), and these remained increased at weeks 18 and 34. The regimen of IL-12 plus liposomal doxorubicin yielded rapid tumor responses and a high response rate in patients with AIDS-KS receiving HAART, and responses were sustained on IL-12 maintenance therapy. A randomized trial of IL-12 in this setting may be warranted. This study is registered at http://www.clinicaltrials.gov as no. NCT00020449.

UR - http://www.scopus.com/inward/record.url?scp=39649118243&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39649118243&partnerID=8YFLogxK

U2 - 10.1182/blood-2007-06-097568

DO - 10.1182/blood-2007-06-097568

M3 - Article

C2 - 17846226

AN - SCOPUS:39649118243

VL - 110

SP - 4165

EP - 4171

JO - Blood

JF - Blood

SN - 0006-4971

IS - 13

ER -