DNA content in cells aspirated from carcinoma of the prostate treated with oestrogenic compounds.
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Observations with cytostatic therapy of generalized prostatic carcinoma (PC) over 5 years are reported, cyclophosphamide (cpa) having been administered to hormone-resistant patients. A standard therapeutic and follow-up scheme, enabling the results to be assessed objectively, had been elaborated. Objective remission or stagnation, confirmed on this basis, was attained in 50%, relief of pain in 60% of the cases. Side effects were negligible. Withdrawal of cytostatics was required in 2 cases. The results indicate that secondary cytostatic therapy significantly potentiated the effect of hormone therapy in generalized PC, and in case of hormone resistance it offers the only chance of therapeutic benefit.
A 62-year-old patient was referred with the suspected diagnosis of Peyronie disease. The patient showed the clinical picture of a beginning malignant priapism with hematogenous metastases from an recurrent prostatic carcinoma. The penile metastases were misdiagnosed as Peyronie disease. Although both clinical pictures show some superficial similarity, Peyronie disease usually fulfills classical criteria which help to clearly distinguish it from neoplastic diseases.
In the past, the treatment options for patients with metastatic prostate cancer that progressed despite castrate levels of testosterone was limited, and no therapies provided an improvement in survival. The majority of these patients had extensive osseous disease, multiple comorbidities, and poor performance status. With the widespread use of prostate-specific antigen (PSA) to monitor their clinical course, patients have presented with less extensive disease and a better performance status. Clinical trial methodology has improved as well, through incorporation of post-therapy changes in PSA to evaluate novel agents. This approach allows more patients to enter clinical trials, and the results show that the majority of these patients will have significant reduction in pain, regression of measurable disease, and suppression of PSA. These data suggest that prostate cancer is not as resistant to chemotherapy as it was once thought to be.
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Chemotherapy was administered in the immediate postoperative period to seventy patients (52 with melanomas and 18 with sarcomas) after a total of eighty-seven major operations, with no morbidity or mortality traceable to the chemotherapy. There was no apparent interference with wound healing or what would be considered a normal postoperative course. Fourteen of these patients (5 with melanomas and 9 with sarcomas) received a combination of radiation anc chemotherapy initiated in the postoperative period, and it was tolerated well. This combination appears to be safe, provided the field of radiation is not so large that is may add significantly to the myelosuppressive effect of chemotherapy and the dosage of concomitantly administered radiopotentiating agent(s) is reduced. Sixteen patients had Bacillus Calmette-Gúerin (BCG) immunotherapy in the immediate postoperative period without complications. This policy of a tight interweaving of modalities is safe, has the theoretic advantage of an earlier concerted attack on microscopic residual tumor, and appears particularly promising in sarcomas.
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Experiences resulting from Emcyt therapy in patients with both newly diagnosed and hormone refractory advanced prostate cancer, as well as on adjuvant to surgery or radiotherapy in earlier disease are presented. Data from trials of the National Prostatic Cancer Project (NPCP) and a series from Roswell Park Memorial Institute (RPMI) were divided into short-term (up to twenty weeks and up to fifty-two weeks in adjuvant trials) and long-term therapy. Baseline disease and patient characteristics and toxicities encountered in these two treatment-duration groups were compared. Patients in a more favorable health or disease status and/or responded to therapy were more frequently in the long-term group. Patients in the long-term group tended to have higher over-all incidences of toxicity; and although many had occurrences begin as early as those in the short-term group, they were able to tolerate the therapy for relatively long periods. The agent is thus both effective and can be given safety for long periods of time.
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The use of cytotoxic chemotherapy in advanced prostate adenocarcinoma has been validated by the recent demonstration of survival benefit in two large randomized phase III trials. Before publication of these landmark trials, SWOG 9916 and TAX 327, no chemotherapeutic regimen had shown survival benefit in the treatment of androgen independent prostate cancer (AIPC). These trials provide new encouragement for the use of chemotherapy in all stages of disease. Improved communication between medical and urologic oncologists and early patient referral for clinical trial participation remains essential for identifying new chemotherapeutic regimens with improved activity in AIPC and for defining the role of chemotherapy in earlier-stage disease. This article discusses the role of chemotherapy as the current standard of care for the treatment of AIPC and provides a historical perspective of the trials that preceded the development of current docetaxel-based regimens.
For >50 years, the standard treatment for advanced prostate cancer has been hormonal therapy. However, all such treated patients eventually develop disease refractory to androgen suppression as manifested by increasing prostate-specific antigen (PSA) levels, progressive disease on radiographic imaging, and ultimately, symptomatic deterioration. Historical perceptions that treatment of hormone-refractory prostate cancer was a largely futile venture have faded over the past decade with the advances in new therapeutic strategies. With the use of PSA values to follow the progress of patients after definitive therapy, physicians are seeing more patients who have failed hormonal therapy yet have no symptoms from their disease. There are standard therapies available for patients who require palliation for symptoms, but there is no consensus on treatment for asymptomatic patients. To date, there has been no definitive increase in survival with any therapy in this group of patients. In addition, several novel drugs have advanced through preclinical testing into early clinical trials. It is these drugs--alone or in combination--that are designed to target strategic tumor pathways in these patients. This article will review a selection of agents that may be potentially useful in this population.
Urologists often are faced with challenges in treating men with metastatic prostate cancer. Although historically chemotherapy has had limited utility in treating this disease, therapeutic nihilism surrounding its use is no longer warranted, as demonstrated by results of 2 recent randomized clinical trials showing that docetaxel-based chemotherapy improves survival in patients with hormone-refractory prostate cancer (HRPC). Although the survival benefit was a modest 2 months, the results hold the promise that docetaxel-based treatment in earlier-stage disease may provide a longer survival advantage. The Cancer and Leukemia Group B (CALGB) 90203 and TAX 3501 studies are phase 3 neoadjuvant and adjuvant radical prostatectomy trials designed to assess the role of docetaxel in patients with high-risk localized disease. These 2 trials, along with the Southwest Oncology Group (SWOG) 9921 trial, which will assess the potential for adjuvant mitoxantrone, are paving the way for earlier systemic treatment. The need for better therapies for patients routinely seen in the urology clinic and the potential for improvements with chemotherapy necessitate an increasing collaboration between urologists and oncologists. Referral to a medical oncologist for a full discussion of treatment options is in the best interest of patients with HRPC, and patients at high-risk for treatment failure should be encouraged to consider clinical trial enrollment.
Estracyt, a conjugate of an alkylating agent with an oestrogenic sterol, was given in a dose of 420 mg daily to a group of 44 postmenopausal patients with very advanced breast carcinoma. Thirty-eight of these were in relapse following chemotherapy and 32 had evidence of distant metastases. Seventeen patients had an objective response and marked or complete alleviation of symptoms, four others had a useful symptomatic response but no beneficial effect was observed in the remainder. Three who had shown no response to previous oestrogen therapy also failed to respond to Estracyt as did all nine patients with hepatic metastases. Oestrogen receptor status and age within the postmenopausal group seemed to have no bearing on the result. Side-effects were minimal with nausea in 18 patients but in only two did this necessitate withdrawal of the drug. Bone marrow depression did not occur. Changes in acute-phase reactant proteins suggested that part of the Estracyt was de-esterified in the liver liberating oestrone but the low incidence of vaginal haemorrhage and the recalcification of bony metastases suggested that on the whole Estracyt behaves as an anti-oestrogen as well as an antimitotic.
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The European Organization for Research on Treatment of Cancer Genitourinary Group performed a multivariate statistical analysis of prognostic factors based on 436 patients entered between 1976 and 1981 in 2 randomized prospective trials that compared 4 different hormonal treatment regimens. Only previously untreated patients with advanced (stage T3/T4/M0 or M1) prostatic cancer were eligible. After identification of prognostic factors by means of univariate analyses a multivariate analysis using Cox's proportional hazards regression model was done. This test identified performance status (according to the Eastern Cooperative Oncology Group scale) as the most important factor, followed by acid phosphatase (more than 2 times normal) for stage M0 cancer patients, and alkaline phosphatase, T category and the presence or absence of associated chronic disease for stage M1 cancer patients. Based on these 4 variables nonbedridden patients with metastatic disease can be divided into 2 groups: poor and good risk patients, with median survivals of 1 and 3 years, respectively. This study shows that routine clinical and laboratory data already provide an excellent indication as to the prognosis.
Prostatic blood flow in 19 patients with prostatic adenocarcinoma was measured by the hydrogen gas clearance method before and during endocrine treatment. Prostatic volume was reduced to 70 per cent of the pre-treatment volume by 3 months after the beginning of treatment. Prostatic blood flow was remarkably depressed in patients who had never had any treatment of the prostatic carcinoma (22.2 +/- 8.3 ml. per minute per 100 gm.), while prostatic blood flow increased significantly after endocrine treatment (56.3 +/- 21.8 ml. per minute per 100 gm.). It was likely that prostatic blood flow increased as the prostate volume decreased. Final histology of serial prostatic biopsy specimens after endocrine treatment, revealed distinct deterioration of tumor cells and slight stromal hyperplasia compared to the initial pre-treatment biopsy. The stromal-epithelial ratio, which was calculated by computer-assisted image analysis, was markedly increased after endocrine treatment. Our study indicated that endocrine treatment caused a growth-inhibitory effect that was accompanied by increased blood flow in the prostatic carcinoma.
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