Temozolomide Plus Thalidomide in Patients With Advanced Melanoma: Results of a Dose-Finding Trial

Hwu, Wen Jen; Krown, Susan E.; Panageas, Katherine S.; Menell, Jennifer H.; Chapman, Paul B.; Livingston, Philip O.; Williams, Linda; Quinn, Carolyn; Houghton, Alan N.

doi:10.1200/jco.2002.09.034

Cited by 62 publications

(34 citation statements)

References 14 publications

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“…Eleven of the trials were published as full reports [8,10,12,13,15,16,19,20,24,26,28], while 10 were available only in abstract form [9, 11, 14, 17, 18, 21-23, 25, 27]. Patient characteristics and trial descriptions for those trials are shown in Table 2.…”

Section: Literature Search Resultsmentioning

confidence: 99%

“…In addition, phase I or II trials investigating singleagent temozolomide (n ϭ 9) [8 -16], temozolomide plus IFN-␣ (n ϭ 6) [17][18][19][20][21][22], and temozolomide plus thalidomide (n ϭ 6) [23][24][25][26][27][28] were reviewed. Eleven of the trials were published as full reports [8,10,12,13,15,16,19,20,24,26,28], while 10 were available only in abstract form [9, 11, 14, 17, 18, 21-23, 25, 27].…”

Section: Literature Search Resultsmentioning

confidence: 99%

“…The literature search located six single-arm phase I or II trials investigating temozolomide plus thalidomide [23][24][25][26][27][28]. Three were available only in abstract form [23,25,27].…”

Section: Temozolomide Plus Thalidomidementioning

confidence: 99%

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Temozolomide for the Treatment of Metastatic Melanoma: A Systematic Review

et al. 2007

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Background. This systematic review examines the role of temozolomide in patients with metastatic melanoma. Outcomes of interest include response rate, progression-free survival, overall survival, quality of life, and adverse effects.Methods. The MEDLINE, EMBASE, and Cochrane Library databases were searched from 1980 through to 2005 using variations on the search terms: melanoma, clinical trial, random, temozolomide, temodal, and temodar. The American Society of Clinical Oncology Annual Meeting proceedings were searched from 1996 to 2005. Relevant articles and abstracts were selected and reviewed by two reviewers, and the reference lists from these sources were searched for additional trials.Results. Two randomized phase III trials and three randomized phase II trials were located. In addition, 21 phase I or II trials investigating single-agent temozolomide, temozolomide plus interferon-␣, and temozolo-

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Section: Literature Search Resultsmentioning

confidence: 99%

Section: Literature Search Resultsmentioning

confidence: 99%

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Temozolomide for the Treatment of Metastatic Melanoma: A Systematic Review

et al. 2007

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“…Hwu et al studied thalidomide in combination with temozolomide in patients with unresectable stage III or stage IV melanoma without brain metastases [58]. TMZ 75 mg/m2/day for 6 weeks was followed by a 2-week break, and thalidomide at 200-400 mg/day.…”

Section: Role In Solid Tumorsmentioning

confidence: 99%

Thalidomide as an anti‐cancer agent

Kumar

Witzig

Rajkumar

2002

J Cellular Molecular Medi

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Thalidomide is a glutamic acid derivative initially introduced as a sedative hypnotic nearly forty years ago. It was withdrawn following numerous reports linking it to a characteristic pattern of congenital abnormalities in babies born to mothers who used the drug for morning sickness. It has gradually been re-introduced into clinical practice over the past two decades, albeit under strict regulation, since it was found to be useful in the management of erythema nodosum leprosum and HIV wasting syndrome. Recognition of its anti-angiogenic effect led to its evaluation in the treatment of various malignancies, where angiogenesis has been shown to play an important role. Numerous clinical trials done over the past four years have confirmed the significant anti-myeloma activity of this drug. It has also shown promise in preliminary trials in the treatment of a variety of different malignant diseases. The mechanisms of its antineoplastic effects continue to be the focus of ongoing research. It has become clear that even though its anti angiogenic effects play a significant role in the anti-tumor activity, there are other properties of this drug which are responsible as well. It also possesses anti-TNF alpha activity, which has led to its evaluation in several inflammatory states. In this concise review, we briefly describe the historical background and pharmacological aspects of this drug. We have concisely reviewed the current knowledge regarding mechanisms of its anti-neoplastic activity and the results of various clinical trials in oncology. Keywords:

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“…The humanized monoclonal antibody Vitaxin, which is directed against the a v b 3 integrin (Posey et al, 2001), and the angiogenesis inhibitor thalidomide, combined with the cytotoxic agent temozolomide (Hwu et al, 2002), are currently being tested in clinical trials for patients with metastatic melanoma. The combination of temozolomide and thalidomide was shown to be well tolerated and had antitumor activity in some patients with advanced melanoma (Hwu et al, 2002). A phase I trial of the angiogenesis inhibitor TNP-470, a derivative of fumagillin, resulted in the induction of long-term stable disease in one patient with progressive metastatic melanoma (Bhargava et al, 1999).…”

Section: Therapeutic Targeting Of Angiogenesis In Melanoma Patientsmentioning

confidence: 99%

Angiogenesis, lymphangiogenesis, and melanoma metastasis

Streit¹,

2003

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The induction of angiogenesis is a critical point in the development of most human tumors -including melanomas. Some of the earliest studies in the field of tumor angiogenesis showed that transplantation of human melanoma fragments into the hamster cheek pouch stimulated blood vessel growth. Since then, numerous studies have demonstrated that human melanomas also induce angiogenesis. The prognostic importance of the degree of melanoma vascularization, however, has remained controversial. Elevated expression of several angiogenic factors, including vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8, has been detected in primary cutaneous melanomas, and the importance of these mediators in promoting melanoma angiogenesis and metastasis has been confirmed in tumor xenotransplant models. Based upon these findings, several clinical trials of angiogenesis inhibitors have been initiated in human melanoma patients and are currently underway. Recent experimental evidence indicates that tumorassociated lymphangiogenesis also plays an important role in mediating tumor spread to regional lymph nodes. These observations have important implications for prognosis and treatment of human melanomas.

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Temozolomide Plus Thalidomide in Patients With Advanced Melanoma: Results of a Dose-Finding Trial

Abstract: The combination of temozolomide and thalidomide was well tolerated and had antitumor activity in patients with advanced melanoma, including elderly patients over 70 years old.

Cited by 62 publications

References 14 publications

Temozolomide for the Treatment of Metastatic Melanoma: A Systematic Review

Temozolomide for the Treatment of Metastatic Melanoma: A Systematic Review

Thalidomide as an anti‐cancer agent

Angiogenesis, lymphangiogenesis, and melanoma metastasis

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