Estramustine phosphate (Estracyt®) in the treatment of prostatic carcinoma

Könyves, I.

doi:10.1007/bf02559635

Cited by 10 publications

(8 citation statements)

References 9 publications

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“…The first hormonally targeted chemotherapeutic agents developed for the treatment of prostate cancer and breast cancer used estrogenic steroid molecules as carriers for various alkylating agents (13,14). Nitrogen mustard compounds were chemically coupled to carrier estrogens for enhancing selectivity and cytotoxicity on estrogen receptor-positive cells (13,14).…”

Section: Hormonal Chemotherapeutic Agentsmentioning

confidence: 99%

“…Nitrogen mustard compounds were chemically coupled to carrier estrogens for enhancing selectivity and cytotoxicity on estrogen receptor-positive cells (13,14). The cytotoxic estrogens, such as estracyte (estramustine), accumulate in the rat prostate due to the presence in the ventral lobe of the prostate of a protein that binds estramustine with high affinity and high capacity (13,14).…”

Section: Hormonal Chemotherapeutic Agentsmentioning

confidence: 99%

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Cancer chemotherapy based on targeting of cytotoxic peptide conjugates to their receptors on tumors

Schally

Nagy²

1999

European Journal of Endocrinology

266

228

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In view of non-specific toxicity of most chemotherapeutic agents against normal cells, the development of targeted chemotherapy is warranted. Efficient targeting of chemotherapeutic drugs to the cancerous area could be of great benefit for patients with advanced or metastatic tumors. Targeted cytotoxic peptide conjugates are hybrid molecules composed of a peptide carrier which binds to receptors on tumors and a cytotoxic moiety. New cytotoxic analogs of LHRH, AN-152 in which doxorubicin (DOX) is linked to ]LHRH, and AN-207 which consists of 2-pyrrolino-DOX (AN-201) coupled to the same carrier, show high-affinity binding and are much less toxic and more effective in vivo than their respective radicals in inhibiting tumor growth in LHRH receptor-positive models of human ovarian, mammary, or prostatic cancer. These results suggest that targeted cytotoxic LHRH analogs such as AN-207 could be considered for treatment of these cancers. The presence of receptors for bombesinlike peptides on a wide variety of tumors prompted us to use some of our bombesin/gastrin-releasing peptide antagonists as carrier molecules. Cytotoxic bombesin analogs, such as AN-215 containing AN-201, might find application in the treatment of small cell lung carcinoma (SCLC), and colorectal, gastric, pancreatic, mammary, and prostatic cancers. Since somatostatin receptors are found in various human neoplasms and the receptor subtypes to which octapeptide analogs bind with high affinity have been identified, we synthesized several cytotoxic somatostatin analogs including AN-162 and AN-238 containing DOX and 2-pyrrolino-DOX respectively, linked to octapeptide RC-121. Cytotoxic somatostatin analog AN-238 efficaciously inhibits growth of human breast or prostate cancers expressing somatostatin receptors-2 and -5 and can be used for receptor-targeted chemotherapy. Cytotoxic somatostatin analogs might also find applications for the therapy of human pancreatic, colorectal, and gastric cancer as well as brain tumors and non-SCLC. Cytotoxic compounds linked to analogs of hormonal peptides like LHRH, bombesin, and somatostatin that can be targeted to certain tumors possessing receptors for those peptides could be an important addition to oncological armamentarium.

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Section: Hormonal Chemotherapeutic Agentsmentioning

confidence: 99%

Section: Hormonal Chemotherapeutic Agentsmentioning

confidence: 99%

Cancer chemotherapy based on targeting of cytotoxic peptide conjugates to their receptors on tumors

Schally

Nagy²

1999

European Journal of Endocrinology

266

228

View full text Add to dashboard Cite

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“…In early studies with hormone receptor targeted chemotherapy, alkylating agents were coupled to estrogenic steroid molecules [168,169]. Also daunorubicin was coupled to β-melanocyte-stimulating hormone for achieving receptor targeting [170].…”

Section: Hormone Receptorsmentioning

confidence: 99%

Anticancer Prodrugs for Application in Monotherapy Targeting Hypoxia, Tumor-Associated Enzymes, and Receptors

Groot¹,

Damen²,

Scheeren

2001

CMC

115

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In order to improve current chemotherapeutic treatment and diminish severe side effects, several prodrug strategies have evolved to achieve site-specific delivery of cytotoxic anticancer agents. This review concentrates on recent developments of antitumor prodrug monotherapy with prodrugs that are designed for direct recognition of tumor-associated factors, such as hypoxia, tumor-associated enzymes and receptors. Firstly, oxygen deficiency in the core of solid tumors leads to enhanced activity of reducing enzymes, like for example nitroreductases, which can be used for site- specific conversion of prodrug to drug. Secondly, some enzymes are present in elevated levels in tumor tissue: beta-glucuronidase leaks from necrotic areas within tumors, while tumor cells for invasive and metastatic activities need several tumor-associated proteases, like plasmin. These enzymes form an attractive target for designing selective prodrugs. Finally, tumor-selective expression of receptors can be exploited for the delivery of antitumor agents. Low molecular weight binding motifs for these receptors can be coupled to cytotoxic drugs in order to obtain tumor-homing conjugates. At present, receptor-binding motifs for a number of receptors that are required for angiogenesis are used for prodrug monotherapy. There exists an increasing body of literature, which describes the complex interplay not only between tumor-associated enzymes, but also between these enzymes and tumor-associated receptors in the process of tumor invasion and metastasis, indicating the feasibility of targeting cytotoxic drugs to these key players in tumor growth. This paper reviews the development and evaluation of anticancer prodrugs, and their application in the various prodrug monotherapy approaches.

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“…In a 1989 review of the early studies, Konyves [7] showed that, in the primary treatment of prostate cancer, the response to estramus tine was only marginally better than to castration. There does appear, however, to be an advantage in patients pre Combined Hormonal and Differentiation Therapy…”

Section: Secondary Hormone Manipulationmentioning

confidence: 99%

“…Possible strategies to prevent hormone refractoriness and for the introduction of cyto-KARGER senting initially with poorly differentiated tumours. The recent demonstration that the use of antiemetics and H, blockers before and during the therapeutic administra tion of estramustine has improved not only the sideeffect profile of the drug but also its acceptability as long-term therapy [7], However, as a second-line treat ment following castration, or other primary hormonal relapse, there does seem to be a place for this combina tion therapy in terms of its subjective though not objec tive response. In a recent review Eisenberger [8] looked at a number of studies, including 561 patients in total, and has shown that, although there is only a 5% com plete and partial response, 25% of patients had a good subjective response for at least 10 months.…”

mentioning

confidence: 99%

The Management of Hormone Refractory Prostate Cancer

Newling¹

1996

Eur Urol

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Estramustine phosphate (Estracyt®) in the treatment of prostatic carcinoma

Cited by 10 publications

References 9 publications

Cancer chemotherapy based on targeting of cytotoxic peptide conjugates to their receptors on tumors

Cancer chemotherapy based on targeting of cytotoxic peptide conjugates to their receptors on tumors

Anticancer Prodrugs for Application in Monotherapy Targeting Hypoxia, Tumor-Associated Enzymes, and Receptors

The Management of Hormone Refractory Prostate Cancer

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