Suramin in hormone-refractory metastatic prostate cancer: a drug with limited efficacy.

Rosen, Peter J.; Mendoza, Evelyn; Landaw, EM; Mondino, Bartly J.; Graves, Michael C.; McBride, James H.; Turcillo, Patricia; deKernion, Jean B.; Belldegrun, Arie S.

doi:10.1200/jco.1996.14.5.1626

Cited by 38 publications

(15 citation statements)

References 27 publications

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“…Similar results were obtained in another study performed by Dawson et al [9]. Rosen et al [10] reported results on 32 assessable patients with HRPC; 9 patients (28%) had a partial response and they concluded that the combination of suramin and hydrocortisone therapy appears to hold limited activity. More recently, Calvo et al [11] found that a fixed higher-dose suramin schedule showed high, although short-lived, activity and good tolerance profile in HRPC patients.…”

Section: Suraminsupporting

confidence: 77%

Role of Chemotherapy in Hormone-Refractory Prostate Cancer

Autorino¹,

Lorenzo

Damiano³

et al. 2003

Urol Int

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Prostate cancer that grows despite castrate levels of testosterone and that no longer responds to any form of hormonal manipulation and for which nonhormonal approaches are required, can be precisely defined as hormone-refractory prostate cancer (HRPC). Until recently, there has been no standard chemotherapeutic approach for HRPC. In this article recent advances in the treatment of HRPC using chemotherapeutic regimens are critically reviewed. We performed a MEDLINE search of the published reports from 1995 to 2002 including chemotherapy in the treatment of HRPC. We critically reviewed a total of 84 clinical trials, of which only 6 were phase III trials, most of the studies being phase II trials. Various chemotherapeutic agents have been used. To date, the major benefits of chemotherapy in the treatment of HRPC are palliative in nature, in terms of reduction of pain and use of analgesics and improvement of performance status, as followed in the most recent trials. There is a promising activity of new drug combinations, such as vinca alkaloids and taxanes in association with estramustine. Mitoxantrone, although with a limited activity, has been shown to provide improvement in pain and quality of life for the patients. Several studies suffer from methodological deficits, such as small number of patients, heterogeneity of enrolled groups or no definitive response criteria. Further phase III studies are necessary to better evaluate the efficacy of the different regimens.

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Section: Suraminsupporting

confidence: 77%

Role of Chemotherapy in Hormone-Refractory Prostate Cancer

Autorino¹,

Lorenzo

Damiano³

et al. 2003

Urol Int

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“…Suramin has been evaluated clinically since the early 1980s. At least 33 trials have been published (e.g., [41][42][43][44][45][46][47][48][49][50]. In all of these trials, suramin was used as a cytotoxic agent at therapeutic plasma concentrations of between 100 and 200 mol/L.…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Suramin Enhanced Paclitaxel Activity in Chemotherapy-Naïve and Paclitaxel-Pretreated Human Breast Xenograft Tumors

Song

Yu²,

Wei³

et al. 2004

Clinical Cancer Research

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We reported induction of broad-spectrum chemoresistance by acidic and basic fibroblast growth factors and chemosensitization by their nonspecific inhibitor suramin at nontoxic and subtherapeutic doses. This study evaluated whether low-dose suramin enhances paclitaxel activity in chemotherapy-naïve and paclitaxel-pretreated human MCF7 breast xenograft tumors in mice. Suramin, 10 mg/kg, and/or paclitaxel, 15 mg/kg, were administered intravenously, twice weekly for 2 to 3 weeks. In addition to conventional end points [tumor size change, median survival time (MST)], we also used clinically relevant end points [partial (PR) and complete response rates (CR); progressive disease (PD); stable disease (SD); time to tumor progression (TTP)]. In chemotherapynaïve mice, the control and suramin groups showed identical TTP (3 days) and MST (21 days). Single-agent paclitaxel produced 47% PR and 24% CR, and prolonged both TTP and MST to 73 days. The addition of suramin further improved the total response rate to 100% with a dramatically greater 63% CR, shortened the time to attain PR and CR, and prolonged TTP and MST to >136 days. In the paclitaxel-pretreated group, single-agent paclitaxel resulted in 67% SD and 33% PD, whereas the combination produced 50% PR and 50% SD. Suramin also significantly enhanced the apoptotic effect of paclitaxel in tumors. In conclusion, suramin improved the activity of paclitaxel in both chemotherapy-naïve and paclitaxel-pretreated animals, without enhancing host toxicity (<10% body weight loss in all groups). These data have led to the initiation of phase I/II trials of paclitaxel and low-dose suramin combination in advanced metastatic breast cancer patients.

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“…We have established a model of micrometastases to bone and liver in chick embryos using the hormone-independent cancer cell line PC-3 which consistently produces metastases in bone and liver. We used the model to evaluate suramin, a promising agent against hormone-refractory prostate cancer [2, 3, 4], by means of a quantitative PCR assay for micrometastases [5]. …”

Section: Introductionmentioning

confidence: 99%