Phase II Study of the Cyclin-Dependent Kinase Inhibitor Flavopiridol Administered to Patients With Advanced Gastric Carcinoma

Schwartz, Gary K.; Ilson, David H.; Saltz, Leonard; O'Reilly, Eileen Mary; Tong, William P.; Maslak, P.; Werner, Jeanine; Perkins, Pam; Stoltz, M.; Kelsen, David P.

doi:10.1200/jco.2001.19.7.1985

Cited by 185 publications

(99 citation statements)

References 9 publications

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“…Flavopiridol, however, did not have a desired eVect in advanced gastric carcinoma (Schwartz et al 2001), non-small-cell lung cancer (Shapiro et al 2001), advanced colorectal cancer (Aklilu et al 2003), androgen-independent prostate cancer (Liu et al 2004), melanoma (Burdette-Radoux et al 2004), endometrial carcinoma (Grendys et al 2005) and advanced soft tissue sarcoma (Morris et al 2006). It did have a modest eVect in mantle cell lymphoma (Kouroukis et al 2003) and advanced renal cell carcinoma (Van Veldhuizen et al 2005).…”

Section: Broad-range Inhibitorsmentioning

confidence: 99%

The CDK inhibitors in cancer research and therapy

Cicenas

Valius²

2011

J Cancer Res Clin Oncol

216

176

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Chemical compounds that interfere with an enzymatic function of kinases are useful for gaining insight into the complicated biochemical processes in mammalian cells. Cyclin-dependent kinases (CDK) play an essential role in the control of the cell cycle and/or proliferation. These kinases as well as their regulators are frequently deregulated in diVerent human tumors. Aberrations in CDK activity have also been observed in viral infections, Alzheimer's, Parkinson's diseases, ischemia and some proliferative disorders. This led to an intensive search for small-molecule CDK inhibitors not only for research purposes, but also for therapeutic applications. Here, we discuss seventeen CDK inhibitors and their use in cancer research or therapy. This review should help researchers to decide which inhibitor is best suited for the speciWc purpose of their research. For this purpose, the targets, commercial availability and IC 50 values are provided for each inhibitor. The review will also provide an overview of the clinical studies performed with some of these inhibitors.

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Section: Broad-range Inhibitorsmentioning

confidence: 99%

The CDK inhibitors in cancer research and therapy

Cicenas

Valius²

2011

J Cancer Res Clin Oncol

216

176

View full text Add to dashboard Cite

show abstract

“…Some of these CDK inhibitors have been piloted in the clinic and the first data from these clinical trials are available (Senderowicz et al, 1998;Stadler et al, 2000;Schwartz et al, 2001). Flavopiridol, the first CDK modulator tested in clinical trials, demonstrated interesting clinical features: cell cycle block at G1 and G2 (consistent with its inhibition of CDK2 and CDK1), induction of apoptosis, promotion of differentiation, inhibition of angiogenic processes and modulation of transcriptional events.…”

Section: Chemical Inhibitors Of Cdkmentioning

confidence: 99%

Targeting the cell cycle for cancer therapy

Carnero

2002

Br J Cancer

134

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Most if not all neoplasias show a directly or indirectly deregulated cell cycle. Targeting its regulatory molecules, the cyclindependent kinases, as a therapeutic mode to develop new anticancer drugs, is being currently explored in both academia and pharmaceutical companies. The development of new compounds is being focused on the many features of the cell cycle with promising preclinical data in most fields. Moreover, a few compounds have entered clinical trials with excellent results maintaining the high hopes. Thus, although too early to provide a cell cycle target based new commercial drug, there is no doubt that it will be an excellent source of new anticancer compounds.

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“…Since the early 1990s flavopiridol was extensively studied in patients with refractory neoplasms, a variety of solid tumors and hematopoietic malignancies. Clinical trials with single flavopiridol were completed for, e. g., advanced gastric cancer, endometrial adenocarcinoma, metastatic melanoma, multiple myeloma, and non-small cell lung cancer in phase II, but only unsatisfying results concerning antitumor activity and toxicities like myelosuppression, diarrhea as well as thromboses were observed (Burdette-Radoux et al, 2004;Dispenzieri et al, 2006;Grendys et al, 2005;Schwartz et al, 2001;Shapiro et al, 2001). Also, no response to flavopiridol administered as 24 hour continuous infusion in chronic lymphocytic leukemia patients was observed (Flinn et al, 2005).…”

Section: Cdk Inhibitors For Cancer Therapymentioning

confidence: 99%