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PubMed2004

[Chemotherapy of the hormone-refractory prostate cancer].

The scepticism dominating the chemotherapy of the hormone-refractory prostate cancer (HRPC) has been replaced by a wave of enthusiasm. Phase II studies with taxane-containing combination therapies could achieve high response rate in some cases, and HRPC can not longer be deemed resistant to chemotherapy. It remains to be seen whether the combinations offer a survival advantage. This will be tested in phase III studies. Palliative chemotherapy should be considered in patients with HRPC if the initial hormone therapy was effective for a short time only and after several hormone therapies have been completed. Since chemotherapy is not yet an established standard therapy of HRPC, patients should be, if possible, included in clinical studies.

Androgen Antagonists↗
PubMed2004

Weekly administration of docetaxel in patients with hormone-refractory prostate cancer: a pilot study on Japanese patients.

OBJECTIVE: Although treatment of hormone-refractory prostate cancer (HRPC) is difficult, a single-agent weekly dose of docetaxel has been reported as a promising regimen for patients with HRPC. The purpose of this study was the investigation of the efficacy of docetaxel for Japanese patients with HRPC. METHODS: Ten patients with HRPC were treated with weekly docetaxel at Tsukuba University Hospital and were evaluated for the responses with respect to serum prostate-specific antigen (PSA), tumor size and survival. Considering the ethnic balance, the dose of docetaxel was reduced to 30 mg/m(2) weekly compared with 36 mg/m(2) in the study reported previously. RESULTS: A biochemical response (>50% decrease in PSA) was observed in five patients (56%; 5/9) with an average time to progression of 4.5 months. In two partial responders as determined by PSA, respective metastatic lesions in bone and soft tissue were also improved. The estimated median survival duration was 6 months. Most of these responses were accompanied by a significant reduction in the requirement for analgesic agents. No severe toxicity of this regimen was observed, except for gastric ulcer in one patient who was excluded from the evaluation. CONCLUSIONS: Weekly administration of docetaxel as a single agent was associated with a high rate of PSA reduction. This treatment is feasible for patients with HRPC, even those who have a poor performance status and extensive prior treatments.

Aged↗
PubMed1988

Hormonal therapy trials in prostatic cancer. An EORTC Genitourinary Group study.

In this paper the authors review the completed and current EORTC Genitourinary Group trials for metastatic carcinoma of the prostate. In terms of time to progression and length of survival, there is no significant difference between any of the effective endocrine treatments that have been studied. The statistical analysis of the different variables used in trials 30,761 and 30,762 determines three risk groups of patients. There is no need for very special laboratory investigations to establish a prognosis. Orchiectomy is the cheapest and safest endocrine treatment in metastatic carcinoma of the prostate.

Androgen Antagonists↗
PubMed2003

Prostate cancer and bone metastases: medical treatment.

Prostate cancer is the most common malignancy in men in the United States. With the long natural history of the disease, management of skeletal morbidity related to advanced prostate cancer becomes a major public health issue. The standard of care in advanced prostate cancer is androgen deprivation therapy. This may accelerate the development of osteoporosis and further exacerbate the risks of having adverse skeletal-related events develop. Recently, the use of bisphosphonates in men who have not responded to androgen deprivation therapy has been shown to reduce the incidence of skeletal-related events with time. Questions remain as to whether bisphosphonates should be broadly applied to earlier stages of the disease or tailored to men at higher risk of having bone-related morbidity. Work is ongoing to improve other approaches to the medical treatment of bone metastases in patients with advanced prostate cancer including the use of radiopharmaceuticals and combined chemotherapy.

Antineoplastic Agents, Hormonal↗
PubMed2003

The evolving role of chemotherapy and other systemic therapies for managing localized prostate cancer.

PURPOSE: The recent literature is reviewed regarding the use of neoadjuvant and adjuvant chemotherapy, and promising new molecular targeted agents in patients with high risk localized prostate cancer. MATERIALS AND METHODS: A MEDLINE literature review was performed of studies evaluating chemotherapy and other systemic therapies for localized prostate cancer. RESULTS: Patients with prostate cancer at high risk for recurrence despite local therapy include those with clinical stage T3 disease, biopsy Gleason scores of 8 to 10 or serum prostate specific antigen greater than 20 ng/ml. Although hormonal therapy has palliative benefit for the majority of patients with metastatic disease, randomized trials have not demonstrated a survival benefit from its administration before surgery for high risk localized disease. Recent trials have shown that cytotoxic chemotherapy has significant activity in hormone refractory prostate cancer, which has led to ongoing clinical trials that are investigating the use of chemotherapy in the neoadjuvant setting. Published and ongoing clinical trials in the use of systemic therapy for localized prostate cancer are reviewed. CONCLUSIONS: Systemic therapy for advanced prostate cancer is improving. Efforts to use such therapies for managing localized disease are ongoing.

Antineoplastic Agents, Hormonal↗
PubMed2005

Update in the management of patients with hormone-refractory prostate cancer.

PURPOSE OF REVIEW: 2004 was a critical year for advances in prostate cancer treatment. The results from two pivotal multicenter phase III randomized studies are the first to demonstrate a survival benefit associated with chemotherapeutic treatment interventions in patients with hormone-refractory prostate cancer. This review will focus on an interpretation of the data from these two studies, the emerging role for chemotherapy in 2005 and beyond, and ongoing areas of clinical research. RECENT FINDINGS: Phase I and II studies have demonstrated biochemical and objective responses achieved with docetaxel-based chemotherapy in men with hormone-refractory prostate cancer. Two pivotal phase III clinical trials, TAX 327 and SWOG 9916 have demonstrated a survival advantage of docetaxel-based chemotherapy over mitoxantrone. Novel targeted therapies under investigation include calcitriol, growth factor-targeted agents, epothilones and others. SUMMARY: We now have a new standard of care for men with metastatic hormone-refractory prostate cancer. Further investigation of docetaxel-based regimens in earlier clinical states of disease is warranted and may demonstrate greater clinical benefit. Additional chemotherapy agents are being studied, and may also add to the future armamentarium available for prostate cancer. The enrolment of patients into these studies is critical to the ongoing evolution of prostate cancer management.

Antineoplastic Agents, Hormonal↗
PubMed1984

The stable state is not an objective response in hormone-escaped carcinoma of prostate.

In some clinical trials the use of criteria of stable response of hormone-escaped prostate cancer is justified on the ground that it delineates patients with markedly improved survival, similar to that of partial regression patients. Forty-three patients with hormone-escaped prostate cancer were studied in order to identify other factors which might also predict improved survival. Fifteen patients received palliative treatment only, 17 secondary hormone therapy and 11 chemotherapy. Only one objective partial regression was seen. Thirty-seven patients have died of prostatic cancer, 3 have died of other causes and 3 remain alive. The mean initial hormone response was 14.8 months, the mean time from progression to death 11.3 months, and the mean time from symptoms to death 5.9 months. There was no significant correlation between length of initial response and survival following progression (r = 0.25). Six features of progression were reviewed. Patients presenting with one feature of progression had a significantly better mean survival, 14.8 months, compared with 8.2 months when multiple features indicated progression. It is concluded that the stable state is not an objective response in hormone-escaped carcinoma of prostate but a reflection of the patient's natural disease progression and that the mode of presentation may be a significant prognostic indicator.

Drug Resistance↗
PubMed1985

Serial prostatic histology. A valid marker of response to hormone treatment.

Serial transrectal needle biopsies were taken from 146 patients (657 specimens) with advanced prostatic cancer (T3/T4, M1/MO) admitted to a trial of two forms of oestrogen therapy. Histological grading by Gleason and Mostofi techniques on the initial biopsy showed no correlation either with extent of disease or its eventual outcome on treatment. Change in grade was dissociated from the response of bone metastases to hormone treatment and did not appear to influence survival. However, the prognosis of 16 patients showing clearance of tumour from their serial biopsies was generally good.

Aged↗
PubMed1985

Bone imaging and serum phosphatases in prostatic carcinoma.

One hundred and twenty-seven patients with locally advanced prostatic cancer were evaluated for the presence and progress of bone metastases before and during hormonal therapy, by serial radionuclide imaging and frequent measurement of plasma acid (tartrate-labile) and alkaline phosphatase. For comparison, serial changes in imaging and phosphatases were classified in each patient into one of six groups. Of 71 patients with negative imaging before treatment, 82% had normal alkaline phosphatase levels and 83% had normal acid phosphatase levels. Of 56 patients with bone metastases at presentation, false negative alkaline and acid phosphatase levels were noted in 18% and 36% respectively, though a few patients eventually developed abnormal levels. Serial plasma biochemistry and particularly alkaline phosphatase showed a response to treatment which was not always obvious on imaging. An assessment of the hepatic component of alkaline phosphatase by reference to plasma gamma glutamyl transpeptidase and isoenzyme electrophoresis was helpful in the evaluation of a false positive result but unnecessary where imaging was positive and phosphatase elevated. It is concluded that serial alkaline phosphatase estimation is essential in the follow-up of patients with prostatic cancer and bone metastases, and probably renders serial imaging studies superfluous once the presence of skeletal metastases has been proven. By comparison, acid phosphatase is a much less effective marker.

Acid Phosphatase↗