Phase II evaluation of suramin in advanced renal cell carcinoma

Schroder, Louis E.; Lew, Danika; Flanigan, Robert C.; Eisenberger, Mario A.; Seay, Thomas E.; Hammond, Neel; Needles, Burton; Crawford, E. David

doi:10.1016/s1078-1439(00)00126-5

Cited by 6 publications

(3 citation statements)

References 9 publications

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“…A phase II trial of suramin was conducted in 26 patients with advanced renal cell carcinoma, but the therapeutic responses were minimal (minor response observed for five patients for >3 months), while the toxic side effects were serious including an immune-mediated thrombocytopenia and Staphylococcus sepsis without neutropenia [Motzer et al, 1992]. Another suramin-based phase II clinical trial in 22 patients with advanced renal cell carcinoma revealed no objective response [Schroder et al, 2001], challenging its therapeutic value in RCC.…”

Section: Targeting Angiogenesis In Rcc: Therapeutic Outcomes and Clinmentioning

confidence: 99%

Targeting vasculature in urologic tumors: Mechanistic and therapeutic significance

Sakamoto

Ryan

Kyprianou

2007

J of Cellular Biochemistry

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Recent advances toward understanding the molecular mechanisms regulating cancer initiation and progression provide new insights into the therapeutic value of targeting tumor vascularity by interfering with angiogenic signaling pathways. The functional contribution of key angiogenic factors toward increased vascularity characterizing metastatic tumors and their therapeutic exploitation is considered in three major urologic malignancies, renal, bladder, and prostate cancer. With the realization that the success of the therapeutic efficacy of the various anti-angiogenic approaches for the treatment of urologic tumors has yet to be proven clinically, the challenge remains to select critical angiogenesis pathways that can be targeted for an individual tumor. Here we discuss the major mechanisms that support formation of vasculature in renal, bladder, and prostate tumors and the current results of targeting of specific molecules/regulators for therapeutic intervention against metastastic disease. Keywordsvascularity; tumor growth; apoptosis; VEGF; bladder cancer; renal cancer; prostate cancer In 2007, there will be an estimated 346,440 new cases diagnosed with urologic cancer in the United States and 54,360 Americans will die from a urologic malignancy (SEER Cancer Statistics Review, http://cancernet.nci.nih.gov/statistics). This mortality rate is alarmingly high as it translates to one individual dying every 9 min in the US due to a urologic tumor and thus a significant health issue.Angiogenesis is an essential process in normal physiological functions such as ovarian cycle in female reproductive system [Kaczmarek et al., 2005] and a contributing factor in disease states such as chronic inflammation, arthritis, cancer, and macular degeneration . During the development of the embryo, mesoderm differentiates into angioblasts; these endothelial cells, not yet organized into a lumen, form primitive vessels toward development of blood vessel network, via vasculogenesis. In the adult, new blood vessels form from preexisting vasculature, via angiogenesis [Risau, 1997], while malignant conditions induce a hypercoagulable state in their hosts [Nash et al., 2001]. By early 1960s it was evident that tumors could elaborate diffusible substances that induce angiogenesis from the host vasculature [Algira et al., 1945;Greenblatt and Shubick, 1968]. The increased tumor vascularity was originally believed to be vasodilation of the host endothelium in response to metabolic waste products from within the tumor . A decade later Dr. Folkman's pioneering work identified angiogenesis as a required phenomenon for tumor growth and metastasis, first defining the potential therapeutic value of agents targeting this process , 1971]. Tumor blood vessels exhibit characteristic markers which are not present in normal angiogenic tissues . After enduring the circulation "journey," metastatic cancer cells can escape out of the endothelial vasculature and in the target tissue via extravasation. How do the metastastic cells signal activa...

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Section: Targeting Angiogenesis In Rcc: Therapeutic Outcomes and Clinmentioning

confidence: 99%

Targeting vasculature in urologic tumors: Mechanistic and therapeutic significance

Sakamoto

Ryan

Kyprianou

2007

J of Cellular Biochemistry

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“…[119][120][121] In a study of 17 patients with hormone-refractory prostate cancer (HRPC), suramin treatment yielded complete response (CR) in 3 patients and PR in 3 patients. 122 Because of suramin's complex pharmacokinetics, narrow therapeutic margin, long half-life (55 days), and high toxicity, 123 producing neuropathy, renal dysfunction, and myelosuppression, serum concentration is usually monitored, and later studies employed blood suramin concentrations less than 200-250 µg/ml.…”

Section: Suraminmentioning

confidence: 99%

“…10 VEGF-A has several isoforms that are generated through alternative splicing. VEGF 121 , VEGF 165 , VEGF 189 , and VEGF 206 have 121, 165, 189, and 206 amino acids, respectively. 11 VEGF 121 lacks heparin affinity, resulting in reduced mitogenic activity.…”

Section: Introductionmentioning

confidence: 99%

Current status and perspective of antiangiogenic therapy for cancer: urinary cancer

2006

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Angiogenesis is considered a prerequisite for solid tumor growth. Antiangiogenic therapy reduces tumor size and extends host survival in a number of preclinical animal models. However, in humans antiangiogenic therapy is a poor promoter of tumor regression and has shown minimal effect on patient survival. In urinary cancers, such as renal cell cancer, prostate cancer, and bladder cancer, advanced refractory disease is a good candidate for antiangiogenic therapy because of its resistance to ordinary chemotherapy, radiotherapy, and hormonal therapy. Unique characteristics of molecular mechanisms underlie the induction of angiogenesis in urinary cancers. In this review, we summarize these unique mechanisms and review the results of clinical trials of antiangiogenic therapy for these cancers, discussing prospects and problems relating to antiangiogenic therapy.

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Suramin

2006

Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions

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Phase II evaluation of suramin in advanced renal cell carcinoma

Cited by 6 publications

References 9 publications

Targeting vasculature in urologic tumors: Mechanistic and therapeutic significance

Targeting vasculature in urologic tumors: Mechanistic and therapeutic significance

Current status and perspective of antiangiogenic therapy for cancer: urinary cancer

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