Phase II trial of thalidomide in renal-cell carcinoma

Escudier, Bernard; Lassau, Nathalie; Couanet, D.; Angevin, Eric; Mesrati, Francine; Leborgne, S.; Garofano, A.; Leboulaire, Christophe; Dupouy, N.; Laplanche, Agnès

doi:10.1093/annonc/mdf213

Cited by 102 publications

(39 citation statements)

References 22 publications

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“…[17][18][19][29][30][31][32] Toxicities were common and included constipation, lethargy, thrombosis, and neuropathy. 31 Despite these sometimes troublesome toxicities, the role of thalidomide was explored In that trial, there was no difference in response rates, progression free survival, or OS. Conversely, thalidomide analogues like LEN have greater potency and better tolerability.…”

Section: Discussionmentioning

confidence: 99%

Phase II study of lenalidomide in patients with metastatic renal cell carcinoma

Choueiri

Dreicer

Rini

et al. 2006

Cancer

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BACKGROUND. Lenalidomide (LEN) is a structural and functional analogue of thalidomide that has demonstrated enhanced immunomodulatory properties and a more favorable toxicity profile. A Phase II, open‐label study of LEN in patients with metastatic renal cell carcinoma (RCC) was conducted to determine its safety and clinical activity. METHODS. Patients with metastatic RCC received LEN orally at a dose of 25 mg daily for the first 21 days of a 28‐day cycle. The primary endpoint was the objective response rate. Time to treatment failure, safety, and survival were secondary endpoints. RESULTS. In total, 28 patients participated in the trial and were included in the current analysis. Three of 28 patients (11%) demonstrated partial responses and continued to be progression‐free for >15 months. Eleven patients (39%) had stable disease that lasted >3 months, including 8 patients who had tumor shrinkage. In total, 6 patients (21%) remained on the trial, and 5 additional patients continued to be followed for survival. The median follow‐up for those 11 patients was 13.5 months (range, 8.3–17.0 months). The median survival had not been reached at the time of the current report. Serious adverse events included fatigue (11%), skin toxicity (11%), and neutropenia (36%). CONCLUSIONS. LEN demonstrated an antitumor effect in metastatic RCC, as evidenced by durable partial responses. LEN toxicities were manageable. Further studies will be required to assess the overall activity of LEN in patients with metastatic RCC. Cancer 2006. © 2006 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Phase II study of lenalidomide in patients with metastatic renal cell carcinoma

Choueiri

Dreicer

Rini

et al. 2006

Cancer

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“…9,75 The frequency increases when thalidomide is combined with myelotoxic chemotherapy. Thrombocytopenia is rare and generally associated with neutropenia.…”

Section: Hematologic Side Effects and Infectionsmentioning

confidence: 99%

Thalidomide for treatment of multiple myeloma: 10 years later

Palumbo

Façon

Sonneveld

et al. 2008

Blood

287

189

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Thalidomide, bortezomib, and lenalidomide have recently changed the treatment paradigm of myeloma. In young, newly diagnosed patients, the combination of thalidomide and dexamethasone has been widely used as induction treatment before autologous stem cell transplantation (ASCT). In 2 randomized studies, consolidation or maintenance with low-dose thalidomide has extended both progression-free and overall survival in patients who underwent ASCT at diagnosis. In elderly, newly diagnosed patients, 3 independent randomized studies have reported that the oral combination of melphalan and prednisone plus thalidomide (MPT) is better than the standard melphalan and prednisone (MP). These studies have shown better progression-free survival, and 2 have shown improved overall survival for patients assigned to MPT. In refractory-relapsed disease, combinations including thalidomide with dexamethasone, melphalan, doxorubicin, or cyclophosphamide have been extensively investigated. The risks of side effects are greater when thalidomide is used in combination with other drugs. Thromboembolism and peripheral neuropathy are the major concern. The introduction of anticoagulant prophylaxis has reduced the rate of thromboembolism to less than 10%. Immediate thalidomide dose reduction or discontinuation when paresthesia is complicated by pain or motor deficit has decreased the severity of neuropathy. Future studies will define the most effective or the best sequence of combinations which could improve life expectancy. (Blood. 2008;111:3968-3977)

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“…372 In spite of some evidence pointing to the activity of thalidomide in renal carcinoma, the high toxicity of the compound at doses needed for the anti-angiogenic activity makes its use unadvisable for the treatment of this type of tumors. [373][374][375] No positive results have been obtained in the treatment of metastatic breast cancer patients. 376 Recent results from a phase III study show that thalidomide does not improve survival in patients receiving cranial irradiation (WBRT) for multiple brain metastases.…”

Section: O T H E R a G E N T S T H A T I N H I B I T A N G I O G E mentioning

confidence: 99%

Anti‐angiogenic drugs: from bench to clinical trials

Quesada

Muñoz‐Chápuli

Medina

2006

Medicinal Research Reviews

143

126

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Angiogenesis, the generation of new capillaries through a process of pre-existing microvessel sprouting, is under stringent control and normally occurs only during embryonic and post-embryonic development, reproductive cycle, and wound repair. However, in many pathological conditions (solid tumor progression, metastasis, diabetic retinopathy, hemangioma, arthritis, psoriasis and atherosclerosis among others), the disease appears to be associated with persistent upregulated angiogenesis. The development of specific anti-angiogenic agents arises as an attractive therapeutic approach for the treatment of cancer and other angiogenesis-dependent diseases. The formation of new blood vessels is a complex multi-step process. Endothelial cells resting in the parent vessels are activated by an angiogenic signal and stimulated to synthesize and release degradative enzymes allowing endothelial cells to migrate, proliferate and finally differentiate to give rise to capillary tubules. Any of these steps may be a potential target for pharmacological intervention. In spite of the disappointing results obtained initially in clinical trials with anti-angiogenic drugs, recent reports with positive results in phases II and III trials encourage expectations in their therapeutic potential. This review discusses the current approaches for the discovery of new compounds that inhibit angiogenesis, with emphasis on the clinical developmental status of anti-angiogenic drugs.

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Phase II trial of thalidomide in renal-cell carcinoma

Cited by 102 publications

References 22 publications

Phase II study of lenalidomide in patients with metastatic renal cell carcinoma

Phase II study of lenalidomide in patients with metastatic renal cell carcinoma

Thalidomide for treatment of multiple myeloma: 10 years later

Anti‐angiogenic drugs: from bench to clinical trials

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