Activity of Thalidomide in AIDS-Related Kaposi’s Sarcoma

Little, Richard F.; Wyvill, Kathleen M.; Pluda, James M.; Welles, Lauri; Marshall, Vickie; Figg, William D.; Newcomb, Fonda M.; Tosato, Giovanna; Feigal, Ellen G.; Steinberg, Seth M.; Whitby, Denise; Goedert, James J.; Yarchoan, Robert

doi:10.1200/jco.2000.18.13.2593

Cited by 260 publications

(113 citation statements)

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“…Indeed clinical trials utilizing two such agents (TNP 470 and thalidomide) are currently ongoing (6,8,9). Recently, lead compounds based on a strategy that aims to cause direct damage to the tumor endothelium resulting in rapid and catastrophic shutdown in the vascular function of the tumor and leading to extensive secondary tumor cell death (11) also have entered clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“…This was based on evidence that thalidomide could inhibit angiogenesis, block tumor necrosis factor alpha (TNF-a), and inhibit intercellular adhesion molecules and basement membrane formation (7). Preliminary results from two Phase II clinical trials showed that there was activity of thalidomide in a 99 subset of patients with KS (8,9). Based on the encouraging results observed with thalidomide and TNP-470, clinical research into the antiangiogenic activities of these and other agents, including interleukin-12 and angiostatin, continues (3,7).…”

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confidence: 99%

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Activity of the Vascular Targeting Agent Combretastatin A-4 Disodium Phosphate in a Xenograft Model of AIDS-Associated Kaposi's Sarcoma

Rojiani

Rise

et al. 2002

Acta Oncologica

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Activity of the Vascular Targeting Agent Combretastatin A-4 Disodium Phosphate in a Xenograft Model of AIDS-Associated Kaposi's Sarcoma

Rojiani

Rise

et al. 2002

Acta Oncologica

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“…Moreover, in the early 1990s, thalidomide was shown to ameliorate symptoms associated with the wasting syndrome of AIDS (3). Today, thalidomide is in clinical trials for HIV ulcers and wasting (3 -6), Crohn's disease (7), rheumatoid arthritis (8,9), chronic host-versus-graft disease (10), Behcet's vasculitis (11), and cancer, including multiple myeloma (12 -15), AIDS Kaposi's sarcoma (16), and other solid tumors (17 -20).…”

Section: Introductionmentioning

confidence: 99%

A thalidomide analogue within vitroantiproliferative, antimitotic, and microtubule-stabilizing activities

Pandit²,

Sackett³

et al. 2006

Molecular Cancer Therapeutics

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We discovered a thalidomide analogue [5-hydroxy-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione (5HPP-33)] with antiproliferative activity against nine cancer cell lines in vitro. Flow cytometric analyses showed that the compound caused G 2 -M arrest, which occurred mainly at the mitotic phase. In addition, immunofluorescence microscopy and in vitro tubulin polymerization studies showed that 5HPP-33 has antimicrotubule activity with a paclitaxel-like mode of action. It is effective against four different paclitaxel-resistant cell lines. Thus, 5HPP-33 represents a potential antitumor agent. [Mol Cancer Ther 2006;5(2):450 -6]

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“…8 Several clinical studies indicate that thalidomide may possess antineoplastic properties in myeloma, 9 melanoma, 10 hormonerefractory prostate carcinoma, 11 high-grade glioma, and Kaposi sarcoma. 12 Several considerations support the potential use of thalidomide in patients with HCC. First, HCC is a very vascular tumor, and it has been demonstrated that angiogenesis is an essential element of tumor progression and metastatic proliferation; 13 thalidomide, as discussed above, is an antiangiogenic agent.…”

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confidence: 99%

Phase II study of thalidomide in patients with unresectable hepatocellular carcinoma

Lin

Brophy

Fisher

et al. 2004

Cancer

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BACKGROUNDThe hypervascular nature of hepatocellular carcinoma (HCC) is well characterized. Recent data have suggested that thalidomide possesses antiangiogenic and immunomodulatory activity. Therefore, the authors initiated a study to assess the efficacy and toxicity of thalidomide in patients with advanced HCC as primary and secondary endpoints, respectively.METHODSInclusion criteria were unresectable HCC with bidimentionally measurable disease, age ≥ 18 years, Eastern Cooperative Oncology Group performance status ≤ 2, and adequate organ function. Thalidomide was administered at a starting dose of 200 mg per day in a 100‐mg‐per‐week dose escalation regimen, up to the maximum tolerated dose or to 800 mg per day. Toxicity was monitored according to the National Cancer Institute Common Toxicity Criteria.RESULTSTwenty‐six of 27 patients were eligible and assessable for toxicity and response. A median daily dose of 300 mg was achieved. One patient experienced near‐complete recovery of α‐fetoprotein levels and a partial radiographic response on computed tomography. Two patients had stable disease during the 16‐week study period. The median duration of progression‐free survival was 42 days. The overall median survival was 123 days. Fatigue and somnolence were the most common side effects, occurring in 81% and 62% of patients, respectively. No Grade 4 hematologic toxicity was observed. Three patients experienced Grade 4 hepatic toxicity (namely, hyperbilirubinemia).CONCLUSIONSWith gradual dose escalation, thalidomide was tolerated in most patients with advanced HCC. However, treatment with thalidomide alone was associated with only a modest response in the treatment of HCC. Cancer 2005. © 2004 American Cancer Society.

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Activity of Thalidomide in AIDS-Related Kaposi’s Sarcoma

Abstract: Oral thalidomide was tolerated in this population at doses up to 1,000 mg/d for as long as 12 months and was found to induce clinically meaningful anti-KS responses in a sizable subset of the patients. Additional studies of this agent in KS are warranted.

Cited by 260 publications

References 55 publications

Activity of the Vascular Targeting Agent Combretastatin A-4 Disodium Phosphate in a Xenograft Model of AIDS-Associated Kaposi's Sarcoma

Activity of the Vascular Targeting Agent Combretastatin A-4 Disodium Phosphate in a Xenograft Model of AIDS-Associated Kaposi's Sarcoma

A thalidomide analogue within vitroantiproliferative, antimitotic, and microtubule-stabilizing activities

Phase II study of thalidomide in patients with unresectable hepatocellular carcinoma

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