Sir—The report of unexplained deaths associated with thalidomide therapy for toxic epidermal necrolysis by Pierre Wolkenstein and colleagues (Nov 14, p 1586), points to the need for a more complete understanding of the putative mechanism(s) of action of this drug. This issue is lent further urgency by the recent licensure of thalidomide by the US Food and Drug Administration for the treatment o...

Thalidomide, which is clinically recognized as an efficient therapeutic agent for multiple myeloma, has been thought to exert antiangiogenic action through an unknown mechanism. We here show a novel mechanism of thalidomide-induced antiangiogenesis in zebrafish embryos. Thalidomide induces the defect of major blood vessels, which is demonstrated by their morphologic loss and confirmed by the de...

The efficacy of thalidomide at doses as low as 50 mg every other day was first reported at the VII International Multiple Myeloma Workshop in Stockholm, Sweden, in September 1999. This article discusses the duration of responses with low-dose thalidomide and the subsequent efficacy with thalidomide combination approaches. The median effective dose of thalidomide was 200 mg/d. Thalidomide's mech...

Introduction Thalidomide was used as a sedative in the 1950s and was withdrawn from the market after initial reports of teratogenicity in 1961. In 1998, the US Food and Drug Administration (FDA) approved the drug as a treatment for erythema nodosum leprosum. The finding of increased angiogenesis in myeloma, coupled with the recognition of the antiangiogenic properties of thalidomide, led to the...

PURPOSE Thalidomide has demonstrated clinical activity in various malignancies including androgen-independent prostate cancer. The development of novel thalidomide analogs with better activity/toxicity profiles is an ongoing research effort. Our laboratory previously reported the in vitro antiangiogenic activity of the N-substituted thalidomide analog CPS11 and the tetrafluorinated analogs CPS4...

Several randomized controlled clinical trials have compared therapy with or without thalidomide in the treatment of advanced non-small cell lung cancer (NSCLC). However, these studies did not produce consistent results. We carried out a meta-analysis to determine the efficacy and safety of thalidomide-based therapy in patients with advanced NSCLC. For this meta-analysis, we selected randomized ...

In this commentary, we describe a model to explain the mechanism of the embryopathy of thalidomide. We propose that thalidomide affects the following pathway during development: insulin-like growth factor I (IGF-I) and fibroblast growth factor 2 (FGF-2) stimulation of the transcription of alphav and beta3 integrin subunit genes. The resulting alphavbeta3 integrin dimer stimulates angiogenesis i...

We performed a meta-analysis of randomized controlled trials comparing thalidomide maintenance with other regimens after induction chemotherapy for multiple myeloma. Overall, 6 trials including 2786 patients were identified. Patients treated with thalidomide maintenance had marginally better overall survival (hazard ratio HR 0.83, P=0.07). The improvement was especially prominent in a subgroup ...

Drug-induced liver injury (DILI) is a leading cause of liver failure and an important safety issue in drug development. Thalidomide is nowadays used for the treatment of several conditions including multiple myeloma (MM). Several adverse effects have been described but liver toxicity was seldom reported. We describe a case of thalidomide-induced hepatitis in a man treated for MM. The clinical s...

In his comprehensive review, Dr. Rajkumar provides a summary of the current status of thalidomide (Thalomid) therapy in cancer. As discussed in the article, it was the teratogenic effects, particularly phocomelia, that prompted researchers to examine thalidomide’s antitumor activity in the 1960s. Although, the results of early phase I trials of thalidomide as an anticancer agent were disappoint...