Use of intravenous fosfestrol tetrasodium (Honvan) infusion in treatment of symptomatic advanced prostate cancer

Williams, AR; Whelan, Peter

doi:10.1038/sj.pcan.4500235

Cited by 5 publications

(4 citation statements)

References 7 publications

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“…Subjective and objective responses are reported in a limited number of patients treated with diethylstilbestrol diphosphate [31,32] or fosfestrol [33,34], Patients with bulky soft tissue disease may be more likely to benefit from i.v. oestrogen therapy [35].…”

Section: Discussionmentioning

confidence: 99%

Diethylstilbestrol in castration‐resistant prostate cancer

et al. 2012

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E 7 2 7What ' s known on the subject? and What does the study add? Diethylstilbestrol (DES) was the fi rst hormone treatment used for prostate cancer and has also shown effectiveness in castration-resistant disease in small studies; however, concerns over thromboembolic toxicity have restricted its use in the past.Over 200 elderly men with castration-resistant prostate cancer were treated with 1 -3 mg of DES, given with 75 mg aspirin and breast bud irradiation. Almost 30% of men showed a signifi cant PSA response and the median time to PSA progression was 4.6 months. Almost 20% of patients with pain had a signifi cant analgesic benefi t. The most important toxicity was thromboembolism in 10% of men. Overall the drug has an acceptable toxicity profi le and offers a palliative benefi t in frail elderly men who may not be fi t for chemotherapy. OBJECTIVE• To assess the effi cacy and toxicity of diethylstilbestrol (DES) in the management of castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS• A total of 231 patients with CRPC received treatment with DES at the Royal Marsden Hospital between August 1992 and August 2000.• The median pre-treatment prostatespecifi c antigen (PSA) level was 221 ng/mL.• DES was used at a dose of 1 -3 mg daily, with aspirin 75 mg.• The primary endpoint was PSA response rate. RESULTS• The PSA response rate (using PSA Working Group criteria) was 28.9%.• The median time to PSA progression was 4.6 months.• Of patients with bone pain, 18% had an improvement in their European Organisation for the Research and Treatment of Cancer pain score.• Thromboembolic complications were seen in 9.9% of all patients. CONCLUSIONS• DES has signifi cant activity in CRPC and can be of palliative benefi t.• DES has an acceptable toxicity profi le in the management of patients with symptomatic CRPC when used at a dose of 1 -3 mg, combined with aspirin and prophylactic breast bud radiotherapy. KEYWORDS

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Section: Discussionmentioning

confidence: 99%

Diethylstilbestrol in castration‐resistant prostate cancer

et al. 2012

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“…Randomized controlled trials comparing fosfestrol to newer agents are required to ascertain its benefit and cost-effectiveness. [15] Williams and Whelan [13] Droz et al [11] Grise et al [14] Our study…”

Section: Discussionmentioning

confidence: 88%

“…Studies have shown that high-dose intravenous fosfestrol is associated with increased risk of cardiac toxicities and thromboembolic events, but the response rates are not increased in comparison to low-dose oral fosfestrol. [11,[13][14][15] There were no Grade 4 toxicities in our study, and only two patients discontinued treatment due to Grade 3 diarrhea. Surprisingly, there were no documented cardiac or thromboembolic events in our study; this contrasts with reports from data from other 3].…”

Section: Discussionmentioning

confidence: 99%

Experience with using fosfestrol for treating metastatic castrate-resistant prostate cancer in resource-limited setting

Kalaiyarasi

Radhakrishnan

Ganesan

et al. 2019

Indian Journal of Medical and Paediatric Oncology

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Background: Fosfestrol is a low-cost estrogen analog that is useful in the management of metastatic prostate cancer in resource-challenged settings. It acts by altering the pituitary axis, adrenal secretion, and 5-alpha reductase activity. Patients and Methods: The outcomes of metastatic castration-resistant prostate cancer patients treated with fosfestrol in our center between June 2012 and December 2015 were analyzed retrospectively. Fosfestrol was given orally at a dose of 120 mg thrice daily. Event was defined as the discontinuation of fosfestrol due to tumor progression or drug toxicity or death due to any cause. The event-free survival (EFS) and overall survival (OS) were calculated by the Kaplan–Meier method. Results: The analysis included 47 patients with a median age of 65 years. Initial Gleason score was available for 41 of 47 patients, of which 17% (7), 39% (16), and 44% (18) were low risk, intermediate risk, and high risk, respectively. The most common site of metastasis was bone (98%). Of 47 patients, 32 (68%) received fosfestrol as the second line of treatment after progression on complete androgen blockade, 14/47 (30%) received it as the third line, and 1/47 received it as the fourth line of treatment. The median prostate-specific antigen (PSA) value at the start of fosfestrol and the nadir PSA value were 43.7 ng/ml and 13.1 ng/ml, respectively. Ninety-one percent ( n = 43) of patients had not been previously treated with chemotherapy (docetaxel). Response of PSA of >50% was observed in 55% ( n = 26) of patients. The median EFS and median OS after the start of fosfestrol were 6.8 and 14.7 months, respectively, with a median follow-up of 10.9 months. Only two patients developed Grade 3 toxicity, both of whom had diarrhea. Conclusions: In resource-challenged settings, oral fosfestrol is an effective, cheap, and safe option for the management of metastatic prostate cancer progressing after first-line complete androgen blockade.

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“…Fosfestrol ([4-{4-(4-phasphono-oxyphenyl)hex-3-en-3-yl}phenoxy]phosphonic acid) is a synthetic estrogen used as an antineoplastic agent. Fosfestrol tetrasodium is an inactive synthetic estrogen which is converted in body to an active estrogen diethylstilbestrol and used in the treatment of prostate cancer [6]. Mitomycin ([6-amino-8a-methoxy-5-methyl-4,7-dioxo-1,1a,2,4,7,8,8a,8b-octahydroazireno [2',3',3,4]pyrrolo-(1,2a)indol-8-yl] methyl carbamate) is in the family of aziridine containing natural product.…”

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confidence: 99%