Oral Chemotherapy in Hormone-Refractory Prostate Carcinoma Patients Unwilling to Be Admitted to Hospital

Serretta, Vincenzo; Altieri, Vincenzo; Morgia, Giuseppe; Siragusa, A; Grande, G. De; Napoli, Matteo; Falsaperla, Mario; Melloni, Darvinio; Allegro, Rosalinda

doi:10.1159/000251187

Cited by 6 publications

(3 citation statements)

References 34 publications

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“…The clearly improved antimetastatic efficacy of PSA9 is an encouraging result, considering that the major cause of death in prostate cancer patients is metastatic disease. 1,2 The reasons why some metastatic sites were more responsive to PSA9 could be that the first two metastatic sites (the lung and lumbar spine) are major targets for metastatic LNCaP cells, and therefore have a relatively high average Figure 3 The antitumor and antimetastatic activity of PSA9 compared with doxorubicin and an untreated control group and the previous data with PSA5 in the orthotopic PSA-positive model (LNCaP). 9 The mean of the control group was set at 100%, and the other values were calculated accordingly.…”

Section: Effects On Lung Liver Inguinal Lymph Nodes and Lumbar Spinmentioning

confidence: 99%

“…1,2 Despite the initial response to androgen deprivation, the disease gradually progresses to a hormone-refractory state as a result of cumulative genetic alterations in tumor cells or the microenvironment. At present, there is no effective therapy for men with hormone-resistant metastatic prostate cancer, and among the approved anticancer agents, taxotere, mitoxantrone and estramustine phosphate, the best results are achieved with taxotere.…”

Section: Introductionmentioning

confidence: 99%

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In vivo evaluation of a novel albumin-binding prodrug of doxorubicin in an orthotopic mouse model of prostate cancer (LNCaP)

Elsadek¹,

Graeser²,

Esser³

et al. 2010

Prostate Cancer Prostatic Dis

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PSA, which is overexpressed in prostate carcinoma, represents a molecular target for selectively releasing an anticancer agent from a prodrug formulation. In this study, we report on the in vivo antitumor efficacy of an efficacious albumin-binding prodrug of doxorubicin (PSA9) that incorporates p-aminobenzyloxycarbonyl (PABC) as a self-immolative spacer in addition to the heptapeptide, Arg-Ser-Ser-Tyr-Tyr-Ser-Leu, which serves as a substrate for PSA. The prodrug is cleaved very efficiently by PSA releasing H-Ser-Leu-PABC-doxorubicin and subsequently doxorubicin in PSA-positive cell lysates and prostate tumor homogenates as the final cleavage product. PSA9 at 3 Â 6 mg kg À1 doxorubicin equivalents (intravenous) was compared with conventional doxorubicin at equitoxic doses (at 3 Â 3 mg kg À1 ; intravenous) in an orthotopic mouse model of prostate cancer using LNCaP lentiviral luciferase-neomycin cells transduced with luciferase. Whereas doxorubicin did not show any efficacy against the primary tumor or metastases, the prodrug reduced the primary tumor by 30-50% and circulating PSA levels, and in addition, showed a pronounced reduction in lung and bone metastases by B77% and B96%, respectively, and a positive trend regarding the activity against liver and lymph-node metastases compared with control and doxorubicin-treated animals. The incorporation of PABC as a self-immolative spacer together with a PSA substrate demonstrates superior antitumor effects over doxorubicin attributed to an efficient cleavage by PSA releasing doxorubicin as the final active agent in prostate tumor homogenates. Using this approach for developing effective prodrugs against prostate cancer, is worthy of further preclinical optimization.

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Section: Effects On Lung Liver Inguinal Lymph Nodes and Lumbar Spinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vivo evaluation of a novel albumin-binding prodrug of doxorubicin in an orthotopic mouse model of prostate cancer (LNCaP)

Elsadek¹,

Graeser²,

Esser³

et al. 2010

Prostate Cancer Prostatic Dis

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“…An oral combination of estramustine phosphate (EMP) and etoposide has been reported to be effective for CRPC [3–5]. However, this combination may be associated with severe side effects such as cardiac complications, leukopenia, and deep venous thrombosis [6].…”

Section: Introductionmentioning

confidence: 99%

Oral etoposide and oral prednisone for the treatment of castration resistant prostate cancer

Zhu

Yao

Zhang

et al. 2013

The Kaohsiung J of Med Scie

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Treatment options for patients with castration-resistant prostate cancer (CRPC) are limited. The purpose of our study was to investigate the safety and efficacy in terms of prostate-specific antigen (PSA) response of a low-dose oral combination of etoposide and prednisone in patients with CRPC. Thirty-nine patients with prostate cancer (median age, 77.9 years) with progressive disease after standard hormonal therapy were enrolled. Etoposide (25 mg, twice daily) and prednisone (5 mg, twice daily) were administered orally. Each cycle comprised 21 consecutive days of treatment followed by a 7-day drug holiday. All patients previously treated with an antiandrogen were required to undergo antiandrogen withdrawal prior to entry into the study. A total of 226 cycles were administered with a median of 6.7 cycles per patient (range, 1-18 cycles). Sixteen of 39 patients (41%) with elevated PSA levels at baseline achieved at least a 50% reduction in PSA levels. Median progression-free survival for all patients was 5.9 months (range, 1-17 months). No Grade 4 toxicities were observed. The predominant toxicities were mucositis, nausea, fatigue, and anemia in twelve, nine, eight, and seven patients, respectively. Hematologic toxicity was infrequent, with no episodes of febrile neutropenia. The combination of low-dose etoposide and prednisone is an efficacious and reasonably well-tolerated oral regimen in the treatment of elderly patients with CRPC. This regimen can be easily administered in an outpatient setting and does not require frequent patient visits.

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Efficacy of estramustine phosphate according to risk classification of castration-resistant prostate cancer

et al. 2012

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Treatment options for patients who progressed to castration-resistant prostate cancer (CRPC) are very limited. The purpose of this study was to assess the efficacy of estramustine phosphate (EMP) in patients with CRPC, grouped according to the risk classification advocated by Armstrong et al. and to identify candidates for EMP treatment. Between March 2003 and July 2010, 82 patients with CRPC were treated with 280 or 560 mg EMP per os daily until disease progression or occurrence of unacceptable adverse events. Prostate-specific antigen (PSA) response and overall survival were evaluated according to risk classification. 52 (67%) patients achieved PSA decline. Rates of PSA decline in the good-, intermediate-, and poor-risk groups were 77, 71, and 25%, respectively, significantly higher in the good- and intermediate-risk groups than the poor-risk group (p=0.03). The median overall survival times in good-, intermediate-, and poor-risk groups were 21, 19, and 9 months, respectively (p=0.005 for good vs intermediate, p=0.001 for intermediate vs poor). When the intermediate-risk group was divided into two subgroups by PSA doubling time (PSADT), men with PSADT≥2 months achieved higher PSA response rate (88%) and longer survival (22 months) than those with PSADT<2 months (53%, 15 months). Patients with good-risk or intermediate-risk with PSA doubling time≥2 months achieved favourable PSA response and survival and may benefit from chemotherapy with EMP.

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Oral Chemotherapy in Hormone-Refractory Prostate Carcinoma Patients Unwilling to Be Admitted to Hospital

Cited by 6 publications

References 34 publications

In vivo evaluation of a novel albumin-binding prodrug of doxorubicin in an orthotopic mouse model of prostate cancer (LNCaP)

In vivo evaluation of a novel albumin-binding prodrug of doxorubicin in an orthotopic mouse model of prostate cancer (LNCaP)

Oral etoposide and oral prednisone for the treatment of castration resistant prostate cancer

Efficacy of estramustine phosphate according to risk classification of castration-resistant prostate cancer

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