Phase II Trial of the Antiangiogenic Agent Thalidomide in Patients With Recurrent High-Grade Gliomas

Fine, Howard A.; Figg, William D.; Jaeckle, Kurt A.; Wen, Patrick Y.; Kyritsis, Athanassios P.; Loeffler, Jay S.; Levin, Victor A.; Black, Peter McL.; Kaplan, Richard; Pluda, James M.; Yung, W.K. Alfred

doi:10.1200/jco.2000.18.4.708

Cited by 386 publications

(181 citation statements)

References 28 publications

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“…Other mediators of angiogenesis (including serum VCAM-1, vWF, and urokinase plasminogen activator soluble receptor) hypothesised to be indirect targets of razoxane were significantly higher in progressive disease patients than in stable disease patients before and after one cycle of treatment (Braybrooke et al, 2000). In a Phase II study of the antiangiogenic agent thalidomide, 16 of 36 patients with recurrent, high-grade gliomas that had radiographic and clinically stable disease had either stable or decreased serum bFGF levels (Fine et al, 2000). Interestingly, serum bFGF levels significantly correlated to survival; patients whose serum bFGF significantly decreased (compared to baseline) survived approximately twice as long (43 weeks) than in those patients whose levels increased beyond the third week of therapy.…”

Section: Serum Plasma and Urine Factorsmentioning

confidence: 99%

Surrogate markers in antiangiogenesis clinical trials

et al. 2003

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Novel antiangiogenic agents currently being developed may ultimately be more effective against solid tumours and less toxic than cytotoxic chemotherapy. As a result of the early clinical trials of angiogenesis inhibitors, investigators are beginning to appreciate the complexity of targeting angiogenesis and the realisation that developing clinically useful antiangiogenic therapy will be more challenging than originally thought. It is now apparent that new methods and surrogate markers to assess these agents' biological activity are crucial for their successful development. This review summarises the currently available clinical data on the development of surrogate markers of angiogenesis inhibitors.

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Section: Serum Plasma and Urine Factorsmentioning

confidence: 99%

Surrogate markers in antiangiogenesis clinical trials

et al. 2003

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“…These include rheumatoid arthritis (Schuler and Ehninger, 1995), the inflammatory and wasting effects of chronic tuberculosis (Klausner et al, 1996), Behcet's disease (Hamuryudan et al, 1998), Crohn's disease (Wettstein and Meagher, 1997;Ehrenpreis et al, 1999;Vasiliauskas et al, 1999) aphthous ulcers (Youle et al, 1989;Alexander and Wilcox, 1997;Jacobson et al, 1997), cachexia (wasting) associated with HIV infection (Sharpstone et al, 1995;Reyes-Teran et al, 1996) and AIDS-related Kaposi's sarcoma (Fife et al, 1998). There is also a wide body of evidence from large-scale clinical trials showing the effectiveness of thalidomide as a treatment for refractory or relapsed multiple myeloma (MM) (Singhal et al, 1999;Hideshima et al, 2000;Juliusson et al, 2000;Kneller et al, 2000;Zomas et al, 2000), and this extends to the treatment of a number of other tumours (Eisen et al, 2000;Fine et al, 2000;Gutheil and Finucane, 2000;Patt et al, 2000;Tseng et al, 2001;Eisen, 2002).…”

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Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers

et al. 2004

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We assessed the safety, tolerability and efficacy of the immunomodulatory drug, CC-5013 (REVIMIDt), in the treatment of patients with metastatic malignant melanoma and other advanced cancers. A total of 20 heavily pretreated patients received a dose-escalating regimen of oral CC-5013. Maximal tolerated dose, toxicity and clinical responses were evaluated and analysis of peripheral T-cell surface markers and serum for cytokines and proangiogenic factors were performed. CC-5013 was well tolerated. In all, 87% of adverse effects were classified as grade 1 or grade 2 according to Common Toxicity Criteria and there were no serious adverse events attributable to CC-5013 treatment. Six patients failed to complete the study, three because of disease progression, two withdrew consent and one was entered inappropriately and withdrawn from the study. The remaining 14 patients completed treatment without dose reduction, with one patient achieving partial remission. Evidence of T-cell activation was indicated by significantly increased serum levels of sIL-2 receptor, granulocyte -macrophage colony-stimulating factor, interleukin-12 (IL-12), tumour necrosis factor-a and IL-8 in nine patients from whom serum was available. However, levels of proangiogenic factors vascular endothelial growth factor and basic foetal growth factor were not consistently affected. This study demonstrates the safety, tolerability and suggests the clinical activity of CC-5013 in the treatment of refractory malignant melanoma. Furthermore, this is the first report demonstrating T-cell stimulatory activity of this class of compound in patients with advanced cancer.

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“…In a basic fibroblast growth factor (bFGF)-induced angiogenesis assay performed in rabbit cornea, it was shown that thalidomide significantly decreased the formation of new vessels 7 and inhibited vascular endothelial growth factor (VEGF)-induced angiogenesis. 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.…”

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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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Phase II Trial of the Antiangiogenic Agent Thalidomide in Patients With Recurrent High-Grade Gliomas

Cited by 386 publications

References 28 publications

Surrogate markers in antiangiogenesis clinical trials

Surrogate markers in antiangiogenesis clinical trials

Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers

Phase II study of thalidomide in patients with unresectable hepatocellular carcinoma

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