goserelin and Adenocarcinoma

Luteinising hormone releasing hormone agonists (LH-RHa) are effective in the treatment of advanced endocrine-sensitive breast cancer in premenopausal patients, but their role in the adjuvant setting has remained controversial for a long time. Tamoxifen for 5 years has been traditionally considered the standard endocrine therapy for premenopausal patients and this is still valid for many patients. However, the recently reported SOFT trial has suggested that adding ovarian function suppression (OFS) to tamoxifen could improve DFS in women at sufficient risk to warrant adjuvant chemotherapy and who remained premenopausal after this therapy. The administration of an aromatase inhibitor plus OFS represents an additional therapeutic option for hormone-receptor positive premenopausal breast cancer patients, according to the combined analysis of the SOFT and TEXT trials. Temporary ovarian suppression induced by LH-RHa has been recognized as an effective strategy to preserve ovarian function from the toxic effects of chemotherapy and is now recommended in young breast cancer patients with endocrine-insensitive tumors. In this review, we discuss recent data on the role of LH-RHa in combination with tamoxifen or with an aromatase inhibitor, and we comment on its role as a strategy to preserve ovarian function in young patients candidates for adjuvant or neo-adjuvant chemotherapy.

Topics: Adenocarcinoma; Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Disease-Free Survival; Estrogens; Female; Fertility Preservation; Gonadotropin-Releasing Hormone; Goserelin; Humans; Neoplasms, Hormone-Dependent; Ovary; Premenopause; Progesterone; Randomized Controlled Trials as Topic; Tamoxifen; Treatment Outcome

In our institution, rotational 3D-conformal radiation therapy (also called conformation therapy) has been applied since the late 1970s to conform the target volume of high-dose radiation to the cancerous tissue while minimizing radiation to the surrounding normal tissues. This technique has been used most commonly to treat prostate cancers in combination with hormonal therapy. The results of Stage B2/C prostate cancer treated with this method were analyzed.. Between 1987 and 1997, 33 cases of prostate cancer were definitively treated with this method: 9 Stage B2 tumors and 24 Stage C tumors. Of these 33 tumors, 3 were well differentiated, 18 were moderately differentiated, and 12 were poorly differentiated. The average patient age was 75.6 years. The median pretreatment PSA value was 23.8 ng/ml. The total radiation dose ranged from 60 Gy to 70 Gy (average: 63.5 Gy) with conventional fractionation. Hormone therapy was administered permanently; the primary hormonal agent was diethylstilbestrol phosphate.. The overall survival rate after 5 years was 58.2% and that after 10 years was 29.6%. The biochemical relapse-free rate after 5 years was 87.0% and that after 10 years was still 87.0%. There were 4 cases of biochemical failure, but no cases of death from prostate cancer. Stage, differentiation, and pretreatment PSA value were not prognostic factors. One of the 2 cases with delayed complications was a case of RTOG Grade 3 gastrointestinal complication.. Rotational 3D-conformal radiation therapy combined with hormone therapy might be promising for the treatment of prostate cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Chlormadinone Acetate; Diethylstilbestrol; Disease-Free Survival; Flutamide; Follow-Up Studies; Gastrointestinal Diseases; Goserelin; Humans; Imaging, Three-Dimensional; Japan; Life Tables; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Prostatic Neoplasms; Radiation Injuries; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Conformal; Retrospective Studies; Rotation; Survival Analysis; Treatment Outcome; Urination Disorders

A 66-year-old, man was referred to our hospital for further examination of multiple pulmonary nodules on chest X-ray performed on medical examination. He was referred to our clinic because his chief complaint was poor urinary stream. Prostatic cancer was suspected on digital rectal examination and magnetic resonance imaging. Serum prostatic specific antigen (PSA) level was 134.9 ng/ml. Histological examination of transrectal prostatic sextant biopsy revealed well differentiated adenocarcinoma of prostate. Abdominal computed tomography-scan, gastro-intestinal tract examination and bone scintigraphy demonstrated no other primary lesions or distant metastases. Under the diagnosis of prostatic cancer with multiple pulmonary metastasis, we performed total androgen blockade (TAB) consisting of luteinizing hormone releasing hormone agonist and flutamide following dietylstilbestrol (DES) intravenous injection therapy. After three months, pulmonary nodules disappeared on chest X-ray and PSA level decreased to below 0.1 ng/ml. Pulmonary nodules also disappeared on CT-scan after six months after TAB. He is alive and free from the recurrence for 42 months.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Diethylstilbestrol; Drug Administration Schedule; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Lung Neoplasms; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Tomography, X-Ray Computed

Prostatic cancer is rarely diagnosed by detection of lung metastases. We report a case of prostatic cancer in a 73-year-old man detected by abnormalities in chest X-ray and serum prostate specific antigen (PSA) level. He was initially admitted to our hospital due to elevation of PSA level. On the first transperineal prostatic needle biopsy, prostatic cancer was not detected and he was followed. Seven months after the first biopsy, chest X-ray revealed multiple abnormal nodules in the lung fields bilaterally and PSA level was again elevated. A second prostatic biopsy and whole-body examination were performed, and he was diagnosed with moderately differentiated prostatic adenocarcinoma with multiple lung metastases. Complete androgen blockade therapy was performed immediately. Two months after the beginning of treatment, PSA level was normalized and the multiple lung metastases had completely disappeared. There has been no evidence of recurrence or PSA relapse 24 months after detection of the prostatic cancer. This is the 26th case of prostatic cancer diagnosed in Japan following detection of multiple lung metastases.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Drug Therapy, Combination; Flutamide; Goserelin; Humans; Lung Neoplasms; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radiography; Treatment Outcome

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Clinical Trials as Topic; Combined Modality Therapy; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Multicenter Studies as Topic; Prostatic Neoplasms; Survival Analysis; Treatment Outcome

Testosterone suppression is the standard treatment for advanced prostate cancer, and it is associated with side-effects that impair patients' quality of life, like sexual dysfunction, osteoporosis, weight gain, and increased cardiovascular risk. We hypothesized that abiraterone acetate with prednisone (AAP) and apalutamide, alone or in combination, can be an effective hormonal therapy also possibly decreasing castration-associated side effects.. Phase II, open-label, randomized, efficacy trial of abiraterone acetate plus prednisone (AAP) and Androgen Deprivation Therapy (ADT) versus apalutamide versus the combination of AAP (without ADT) and apalutamide. Key eligibility criteria are confirmed prostate adenocarcinoma; biochemical relapse after definitive treatment (PSA ≥ 4 ng/ml and doubling time less than 10 months, or PSA ≥ 20 ng/ml); newly diagnosed locally advanced or metastatic prostate cancer; asymptomatic to moderately symptomatic regarding bone symptoms. Patients with other histology besides adenocarcinoma or previous use of hormonal therapy or chemotherapy were excluded.. There is an urgent need to study and validate regimens such as new hormonal agents that may add benefit to castration with an acceptable safety profile. We aim to evaluate if apalutamide in monotherapy or in combination with AAP is an effective and safety hormonal treatment that can spare patients of androgen deprivation therapy.. This trial was registered in ClinicalTrials.gov on October 16, 2017, under Identifier: NCT02867020.

Topics: Abiraterone Acetate; Adenocarcinoma; Androgen Receptor Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Goserelin; Humans; Male; Patient Reported Outcome Measures; Prednisone; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Testosterone; Thiohydantoins; Treatment Outcome

The NRG/RTOG 9413 study showed that whole pelvic radiotherapy (WPRT) plus neoadjuvant hormonal therapy (NHT) improved progression-free survival in patients with intermediate-risk or high-risk localised prostate cancer compared with prostate only radiotherapy (PORT) plus NHT, WPRT plus adjuvant hormonal therapy (AHT), and PORT plus AHT. We provide a long-term update after 10 years of follow-up of the primary endpoint (progression-free survival) and report on the late toxicities of treatment.. The trial was designed as a 2 × 2 factorial study with hormonal sequencing as one stratification factor and radiation field as the other factor and tested whether NHT improved progression-free survival versus AHT, and NHT plus WPRT versus NHT plus PORT. Eligible patients had histologically confirmed, clinically localised adenocarcinoma of the prostate, an estimated risk of lymph node involvement of more than 15% and a Karnofsky performance status of more than 70, with no age limitations. Patients were randomly assigned (1:1:1:1) by permuted block randomisation to receive either NHT 2 months before and during WPRT followed by a prostate boost to 70 Gy (NHT plus WPRT group), NHT 2 months before and during PORT to 70 Gy (NHT plus PORT group), WPRT followed by 4 months of AHT (WPRT plus AHT group), or PORT followed by 4 months of AHT (PORT plus AHT group). Hormonal therapy was combined androgen suppression, consisting of goserelin acetate 3·6 mg once a month subcutaneously or leuprolide acetate 7·5 mg once a month intramuscularly, and flutamide 250 mg twice a day orally for 4 months. Randomisation was stratified by T stage, Gleason Score, and prostate-specific antigen concentration. NHT was given 2 months before radiotherapy and was continued until radiotherapy completion; AHT was given at the completion of radiotherapy for 4 months. The primary endpoint progression-free survival was analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00769548. The trial has been terminated to additional follow-up collection and this is the final analysis for this trial.. Between April 1, 1995, and June 1, 1999, 1322 patients were enrolled from 53 centres and randomly assigned to the four treatment groups. With a median follow-up of 8·8 years (IQR 5·07-13·84) for all patients and 14·8 years (7·18-17·4) for living patients (n=346), progression-free survival across all timepoints continued to differ significantly across the four treatment groups (p=0·002). The 10-year estimates of progression-free survival were 28·4% (95% CI 23·3-33·6) in the NHT plus WPRT group, 23·5% (18·7-28·3) in the NHT plus PORT group, 19·4% (14·9-24·0) in the WPRT plus AHT group, and 30·2% (25·0-35·4) in the PORT plus AHT group. Bladder toxicity was the most common grade 3 or worse late toxicity, affecting 18 (6%) of 316 patients in the NHT plus WPRT group, 17 (5%) of 313 in the NHT plus PORT group, 22 (7%) of 317 in the WPRT plus AHT group, and 14 (4%) of 315 in the PORT plus AHT group. Late grade 3 or worse gastrointestinal adverse events occurred in 22 (7%) of 316 patients in the NHT plus WPRT group, five (2%) of 313 in the NHT plus PORT group, ten (3%) of 317 in the WPRT plus AHT group, and seven (2%) of 315 in the PORT plus AHT group.. In this cohort of patients with intermediate-risk and high-risk localised prostate cancer, NHT plus WPRT improved progression-free survival compared with NHT plus PORT and WPRT plus AHT at long-term follow-up albeit increased risk of grade 3 or worse intestinal toxicity. Interactions between radiotherapy and hormonal therapy suggests that WPRT should be avoided without NHT.. National Cancer Institute.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Canada; Chemoradiotherapy; Dose Fractionation, Radiation; Drug Administration Schedule; Flutamide; Goserelin; Humans; Kallikreins; Leuprolide; Male; Neoplasm Grading; Neoplasm Staging; Progression-Free Survival; Prostate-Specific Antigen; Prostatic Neoplasms; Time Factors; United States

Trial RTOG 9202 was a phase 3 randomized trial designed to determine the optimal duration of androgen deprivation therapy (ADT) when combined with definitive radiation therapy (RT) in the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate. Long-term follow-up results of this study now available are relevant to the management of this disease.. Men (N=1554) with adenocarcinoma of the prostate (cT2c-T4, N0-Nx) with a prostate-specific antigen (PSA) <150 ng/mL and no evidence of distant metastasis were randomized (June 1992 to April 1995) to short-term ADT (STAD: 4 months of flutamide 250 mg 3 times per day and goserelin 3.6 mg per month) and definitive RT versus long-term ADT (LTAD: STAD with definitive RT plus an additional 24 months of monthly goserelin).. Among 1520 protocol-eligible and evaluable patients, the median follow-up time for this analysis was 19.6 years. In analysis adjusted for prognostic covariates, LTAD improved disease-free survival (29% relative reduction in failure rate, P<.0001), local progression (46% relative reduction, P=.02), distant metastases (36% relative reduction, P<.0001), disease-specific survival (30% relative reduction, P=.003), and overall survival (12% relative reduction, P=.03). Other-cause mortality (non-prostate cancer) did not differ (5% relative reduction, P=.48).. LTAD and RT is superior to STAD and RT for the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate and should be considered the standard of care.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Androgen Antagonists; Combined Modality Therapy; Disease-Free Survival; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Time Factors; Treatment Outcome

This study evaluated the baseline patient characteristics associated with the time to biochemical progression and overall survival in patients who participated in a phase II trial on zoledronic acid combined with the initial androgen-deprivation therapy for treatment-naïve bone-metastatic prostate cancer.. Patients received zoledronic acid 4 mg intravenously every 4 weeks for up to 24 months, concomitantly started with bicalutamide 80 mg orally every day and goserelin acetate 10.8 mg subcutaneously every 12 weeks.. A total of 53 Japanese patients were enrolled between July 2008 and April 2010, and 52 patients were evaluable. Median follow-up period was 41.6 months. Updated median time to biochemical progression was 25.9 months (95 % confidence interval 14.5-49.9). Higher serum bone-specific alkaline phosphatase was an independent risk factor for time to biochemical progression based on multivariate analysis (hazard ratio 6.51; 95 % confidence interval 2.71-15.62; P < 0.001). Median time to biochemical progression for patients with serum bone-specific alkaline phosphatase level higher than 26 μg/L was 12.7 months. Multivariate analysis indicated that higher serum C-terminal telopeptide of type I collagen independently increased the risk of death (hazard ratio 9.62; 95 % confidence interval 2.11-43.89; P = 0.003). Median overall survival for patients with serum C-terminal telopeptide of type I collagen level higher than 8.0 ng/ml was 31.1 months.. Baseline bone markers can be useful as predictors for disease progression and survival time in patients with bone metastasis from treatment-naïve prostate cancer treated with upfront zoledronic acid concomitantly started with androgen-deprivation therapy.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Alkaline Phosphatase; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Bone Neoplasms; Diphosphonates; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Therapy, Combination; Follow-Up Studies; Goserelin; Humans; Imidazoles; Japan; Male; Middle Aged; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Risk Factors; Survival Rate; Time Factors; Tosyl Compounds; Zoledronic Acid

Prostate cancer patients at increased risk for relapse after prostatectomy were treated in a neoadjuvant study with androgen deprivation therapy (ADT) in combination with cixutumumab, an inhibitory fully human monoclonal antibody against IGF receptor 1 (IGF-IR).. A clinical trial with prospective collection of serum and tissue was designed to test the potential clinical efficacy of neoadjuvant IGF-IR blockade combined with ADT in these patients. The effect of body mass index (BMI) on response of IGF-IR/insulin components to IGF-IR blockade was also examined.. Eligibility for the trial required the presence of high-risk prostate adenocarcinoma. Treatment consisted of bicalutamide, goserelin, and cixutumumab for 13 weeks before prostatectomy. Here we report on an analysis of serum samples from 29 enrolled patients. Changes in IGF and glucose homeostasis pathways were compared to control samples from patients in a concurrent clinical trial of neoadjuvant ADT alone.. Significant increases were seen in GH (P = .001), IGF-I (P < .0001), IGF-II (P = .003), IGF binding protein (IGFBP)-3 (P < .0001), C-peptide (P = .0038), and insulin (P = .05) compared to patients treated with ADT alone. IGFBP-1 levels were significantly lower in the cixutumumab plus ADT cohort (P = .001). No significant changes in blood glucose were evident. Patients with BMIs in the normal range had significantly higher GH (P < .05) and IGFBP-1 (P < 0.5) levels compared to overweight and obese patients.. Patients with IGF-IR blockade in combination with ADT demonstrated significant changes in IGF and glucose homeostasis pathway factors compared to patients receiving ADT alone. In the patients receiving combination therapy, patients with normal BMI had serum levels of glucose homeostasis components similar to individuals in the ADT-alone cohort, whereas patients with overweight and obese BMIs had serum levels that differed from the ADT cohort.

Topics: Adenocarcinoma; Androgen Antagonists; Anilides; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Body Mass Index; Cohort Studies; Goserelin; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 1; Male; Neoadjuvant Therapy; Nitriles; Obesity; Prostatectomy; Prostatic Neoplasms; Receptor, IGF Type 1; Risk; Secondary Prevention; Somatomedins; Tosyl Compounds; United States

To evaluate the feasibility of administering sunitinib in combination with androgen deprivation therapy and external-beam intensity modulated radiation therapy (XRT) in patients with localized high-risk prostate cancer.. Seventeen men with localized adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or prostate-specific antigen >20 ng/mL received initial androgen deprivation (leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50 mg daily) for 4-8 weeks before oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks after XRT (75.6 Gy in 42 fractions to prostate and seminal vesicles). A 3+3 sequential dose-escalation design was used to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose of sunitinib.. Sunitinib at 12.5- and 25-mg dose levels was well tolerated. The first 4 patients enrolled at 37.5 mg experienced a DLT during lead-in, and a drug interaction between sunitinib and bicalutamide was suspected. The protocol was revised and concurrent bicalutamide omitted. Of the next 3 patients enrolled at 37.5 mg, 2 of 3 receiving concurrent therapy experienced DLTs during radiation: grade 3 diarrhea and grade 3 proctitis, respectively. Only 1 of 7 patients completed sunitinib at 37.5 mg daily, whereas 3 of 3 patients (25 mg as starting dose) and 3 of 4 patients (25 mg as reduced dose) completed therapy.. The feasibility of combined vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR) inhibitor therapy, androgen deprivation, and radiation therapy for prostate cancer was established. Using a daily dosing regimen with lead-in, concurrent, and post-XRT therapy, the recommended phase 2 dose of sunitinib is 25 mg daily.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents; Combined Modality Therapy; Drug Interactions; Feasibility Studies; Goserelin; Humans; Indoles; Leuprolide; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Grading; Neoplasm Staging; Nitriles; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Pyrroles; Radiotherapy, Intensity-Modulated; Seminal Vesicles; Sunitinib; Tosyl Compounds

Although endocrine therapy has been used for decades, its influence on the expression of microRNAs (miRNAs) in clinical tissue specimens has not been analyzed. Moreover, the effects of the TMPRSS2:ERG fusion on the expression of miRNAs in hormone naïve and endocrine-treated prostate cancers are poorly understood.. We used clinical material from a neoadjuvant trial consisting of 28 men treated with goserelin (n = 8), bicalutamide (n = 9), or no treatment (n = 11) for 3 months prior to radical prostatectomy. Freshly frozen specimens were used for microarray analysis of 723 human miRNAs. Specific miRNA expression in cancer, benign epithelium and stromal tissue compartments was predicted with an in silico Bayesian modeling tool.. The expression of 52, 44, and 34 miRNAs was affected >1.4-fold by the endocrine treatment in the cancer, non-malignant epithelium, and stromal compartments, respectively. Of the 52 miRNAs, only 10 were equally affected by the two treatment modalities in the cancer compartment. Twenty-six of the 52 genes (50%) showed AR binding sites in their proximity in either VCaP or LNCaP cell lines. Forty-seven miRNAs were differentially expressed in TMPRSS2:ERG fusion positive compared with fusion negative cases. Endocrine treatment reduced the differences between fusion positive and negative cases.. Goserelin treatment and bicalutamide treatment mostly affected the expression of different miRNAs. The effect clearly varied in different tissue compartments. TMPRSS2:ERG fusion positive and negative cases showed differential expression of miRNAs, and the difference was diminished by androgen ablation.

Topics: Adenocarcinoma; Anilides; Antineoplastic Agents; Computer Simulation; Gene Expression Regulation, Neoplastic; Gene Fusion; Goserelin; Humans; In Situ Hybridization, Fluorescence; Male; MicroRNAs; Neoadjuvant Therapy; Nitriles; Oligonucleotide Array Sequence Analysis; Oncogene Proteins, Fusion; Prostatectomy; Prostatic Neoplasms; Tosyl Compounds; Tumor Cells, Cultured

To ascertain whether biochemical response to neoadjuvant androgen-deprivation therapy (ADT) before radiotherapy (RT), rather than duration, is the critical determinant of benefit in the multimodal treatment of localized prostate cancer, by comparing outcomes of subjects from the Canadian multicenter 3- vs 8-month trial with a pre-RT, post-hormone PSA (PRPH-PSA) < or =0.1 ng/ml vs those >0.1 ng/ml.. From 1995 to 2001, 378 men with localized prostate cancer were randomized to 3 or 8 months of neoadjuvant ADT before RT. On univariate analysis, survival indices were compared between those with a PRPH-PSA < or =0.1 ng/ml vs >0.1 ng/ml, for all patients and subgroups, including treatment arm, risk group, and gleason Score. Multivariate analysis identified independent predictors of outcome.. Biochemical disease-free survival (bDFS) was significantly higher for those with a PRPH-PSA < or =0.1 ng/ml compared with PRPH-PSA >0.1 ng/ml (55.3% vs 49.4%, p = 0.014). No difference in survival indices was observed between treatment arms. There was no difference in bDFS between patients in the 3- and 8-month arms with a PRPH-PSA < or =0.1 ng/ml nor those with PRPH-PSA >0.1 ng/ml. bDFS was significantly higher for high-risk patients with PRPH-PSA < or =0.1 ng/ml compared with PRPH-PSA >0.1 ng/ml (57.0% vs 29.4%, p = 0.017). Multivariate analysis identified PRPH-PSA (p = 0.041), Gleason score (p = 0.001), initial PSA (p = 0.025), and T-stage (p = 0.003), not ADT duration, as independent predictors of outcome.. Biochemical response to neoadjuvant ADT before RT, not duration, appears to be the critical determinant of benefit in the setting of combined therapy. Individually tailored ADT duration based on PRPH-PSA would maximize therapeutic gain, while minimizing the duration of ADT and its related toxicities.

Topics: Adenocarcinoma; Aged; Analysis of Variance; Androgen Antagonists; Antineoplastic Agents, Hormonal; Disease-Free Survival; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Time Factors

We did a randomised phase 3 trial assessing the benefit of addition of long-term androgen suppression with a luteinising-hormone-releasing hormone (LHRH) agonist to external irradiation in patients with prostate cancer with high metastatic risk. In this report, we present the 10-year results.. For this open-label randomised trial, eligible patients were younger than 80 years and had newly diagnosed histologically proven T1-2 prostatic adenocarcinoma with WHO histological grade 3 or T3-4 prostatic adenocarcinoma of any histological grade, and a WHO performance status of 0-2. Patients were randomly assigned (1:1) to receive radiotherapy alone or radiotherapy plus immediate androgen suppression. Treatment allocation was open label and used a minimisation algorithm with institution, clinical stage of the disease, results of pelvic-lymph-node dissection, and irradiation fields extension as minimisation factors. Patients were irradiated externally, once a day, 5 days a week, for 7 weeks to a total dose of 50 Gy to the whole pelvis, with an additional 20 Gy to the prostate and seminal vesicles. The LHRH agonist, goserelin acetate (3·6 mg subcutaneously every 4 weeks), was started on the first day of irradiation and continued for 3 years; cyproterone acetate (50 mg orally three times a day) was given for 1 month starting a week before the first goserelin injection. The primary endpoint was clinical disease-free survival. Analysis was by intention to treat. The trial is registered at ClinicalTrials.gov, number NCT00849082.. Between May 22, 1987, and Oct 31, 1995, 415 patients were randomly assigned to treatment groups and were included in the analysis (208 radiotherapy alone, 207 combined treatment). Median follow-up was 9·1 years (IQR 5·1-12·6). 10-year clinical disease-free survival was 22·7% (95% CI 16·3-29·7) in the radiotherapy-alone group and 47·7% (39·0-56·0) in the combined treatment group (hazard ratio [HR] 0·42, 95% CI 0·33-0·55, p<0·0001). 10-year overall survival was 39·8% (95% CI 31·9-47·5) in patients receiving radiotherapy alone and 58·1% (49·2-66·0) in those allocated combined treatment (HR 0·60, 95% CI 0·45-0·80, p=0·0004), and 10-year prostate-cancer mortality was 30·4% (95% CI 23·2-37·5) and 10·3% (5·1-15·4), respectively (HR 0·38, 95% CI 0·24-0·60, p<0·0001). No significant difference in cardiovascular mortality was noted between treatment groups both in patients who had cardiovascular problems at study entry (eight of 53 patients in the combined treatment group had a cardiovascular-related cause of death vs 11 of 63 in the radiotherapy group; p=0·60) and in those who did not (14 of 154 vs six of 145; p=0·25). Two fractures were reported in patients allocated combined treatment.. In patients with prostate cancer with high metastatic risk, immediate androgen suppression with an LHRH agonist given during and for 3 years after external irradiation improves 10-year disease-free and overall survival without increasing late cardiovascular toxicity.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Canada; Cardiovascular Diseases; Chemotherapy, Adjuvant; Cyproterone Acetate; Disease-Free Survival; Dose Fractionation, Radiation; Drug Administration Schedule; Europe; Fractures, Bone; Goserelin; Humans; Israel; Kaplan-Meier Estimate; Lymphatic Metastasis; Male; Neoplasm Invasiveness; Neoplasm Staging; Prostatic Neoplasms; Risk Assessment; Russia; Time Factors; Treatment Outcome

To determine whether GnRHa administration before and during combination chemotherapy for breast cancer could preserve posttreatment ovarian function in young women or not.. Prospective randomized controlled study.. Department of Obstetrics and Gynecology, Mansura University Hospital, Mansura, Egypt.. Eighty patients with unilateral adenocarcinoma of the breast and with no metastasis who had undergone modified radical mastectomy or breast-conserving surgery plus full axillary lymph node dissection were included in the study. Patients were assigned randomly to receive combined GnRHa and chemotherapy or chemotherapy alone. One woman in each group dropped out.. Return of spontaneous menstruation and ovulation. Hormonal changes (FSH, LH, E(2), P) during and after the course of treatment.. In the study group, 89.6% resumed menses and 69.2% resumed spontaneous ovulation within 3-8 months of termination of the GnRHa/chemotherapy cotreatment; 11.4% experienced hypergonadotrophic amenorrhoea and ovarian failure 8 months after treatment. In the control group (chemotherapy without GnRHa), 33.3% resumed menses and 25.6% resumed normal ovarian activity. The median FSH and LH concentrations, 6 months after completion of the GnRHa/chemotherapy cotreatment group, were significantly less than the control group. During the GnRHa/chemotherapy cotreatment the concentrations of FSH, LH, and P decreased to almost prepubertal levels. However, within 1-3 months after the last GnRHa injection, an increase in LH and FSH concentrations was detected, followed several weeks later in by an increase in P concentrations to within normal levels.. GnRHa administration before and during combination chemotherapy for breast cancer may preserve posttreatment ovarian function in women <40 years. Long-term studies are required.

Topics: Adenocarcinoma; Adult; Amenorrhea; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Drug Administration Schedule; Estradiol; Female; Fertility Agents, Female; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Goserelin; Humans; Infertility, Female; Luteinizing Hormone; Lymph Node Excision; Mastectomy; Menstruation; Ovary; Ovulation; Primary Ovarian Insufficiency; Progesterone; Prospective Studies; Time Factors; Treatment Outcome

In this study, we investigated the shrinking effect of concurrent three-dimensional conformal radiotherapy (3D-CRT) and androgen deprivation (AD) on prostate volume, and its possible impact on the dose received by the rectum and bladder during the course of 3D-CRT. The difference between the prostatic volumes determined on pre-treatment planning CT (PL-CT) and post-treatment CT (PT-CT) following a 3D-CRT course was assessed in 52 patients with localised prostate carcinoma. The changes in mean prostate volume when compared with PL-CT and PT-CT-based measurements were assessed. The pre- and post-treatment mean prostate volumes for the whole study population were 49.7 cm(3) and 41.0 cm(3) (p _ 0.02), respectively. The study cohort was divided into two groups depending on the duration of neoadjuvant androgen deprivation (NAD): 23 patients (44.7%) were designated as "short NAD" (< or =3 months; SNAD) and the remaining 29 (55.3%) as "long NAD" (>3 months; LNAD). Patients on SNAD experienced a significantly greater reduction in prostate volume compared with those on LNAD (14.1% vs 5.1%; p _ 0.03). A significant increase in rectum V(40-60) values in PT-CT compared with PL-CT was demonstrated. LNAD patients had significantly higher rectal V(50-70) values at PT-CT compared with the SNAD group. There was a significant decline in V(30)-V(75) bladder values in PT-CT compared with PL-CT in the SNAD group. In conclusion, a higher prostate volume reduction during 3D-CRT was demonstrated when RT planning was performed within 3 months of NAD. However, this reduction and daily organ motion may lead to an unpredictable increase in rectal doses.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Administration Schedule; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Nitriles; Prostatic Neoplasms; Radiation Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Conformal; Rectum; Tomography, X-Ray Computed; Tosyl Compounds; Treatment Outcome; Urinary Bladder

To study whether use of neoadjuvant androgen deprivation therapy (N-ADT) combined with whole pelvic radiotherapy (WPRT) for high-risk prostate cancer patients was associated with survival benefit over prostate radiotherapy (PORT) only.. Between 1999 and 2004, 162 high-risk prostate cancer patients were treated with radiotherapy combined with long-term androgen deprivation therapy (L-ADT). Patients were prospectively assigned into two groups: A (N-ADT + WPRT + L-ADT) n = 70 pts, B (PORT + L-ADT) n = 92 pts.. The 5-year actuarial overall survival (OS) rates were 89% for A and 78% for B (P = .13). The 5-year actuarial cause specific survival (CSS) rates were A = 90% and B = 79% (P = .01). Biochemical progression-free survival (bPFS) rates were 52% versus 40% (P = .07), for groups A and B, respectively.. The WPRT combined with N-ADT compared to PORT for high-risk patients resulted in improvement in CSS and bPFS; however no OS benefit was observed.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Flutamide; Goserelin; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoadjuvant Therapy; Neoplasms, Hormone-Dependent; Poland; Prospective Studies; Prostatic Neoplasms; Radiotherapy, Conformal; Risk Factors

We determined the risk of recurrence in men enrolled on a randomized trial for prostate cancer who were treated with radiation therapy (RT) alone or in conjunction with combined or less than combined androgen suppression therapy (AST).. Between 1995 and 2001, 206 men with localized but unfavorable-risk adenocarcinoma of the prostate were randomly assigned to receive RT or RT and AST, which was defined as 6 months of both a luteinizing hormone-releasing hormone agonist and an antiandrogen. A post-random assignment hypothesis that was generated by multivariable Cox regression analyses was used to evaluate whether the risk of prostate-specific antigen (PSA) recurrence was significantly associated with months of antiandrogen use; regression analysis adjusted for known prognostic factors, comorbidity score, and medications that can elevate liver function tests sufficiently to necessitate discontinuation of the antiandrogen.. After a median follow-up of 8.2 years (interquartile range,7.0 to 9.5 years), 81 men sustained PSA recurrence. An increasing PSA level (P < .001); Gleason score of 8, 9, or 10 (P < .001); and clinical category T2 disease (P = .005) were significantly associated with an increased risk of recurrence. However, recurrence risk was significantly decreased (adjusted hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = .001) with each additional month of antiandrogen use after analysis was adjusted for these known prognostic factors.. Men with localized but unfavorable-risk prostate cancer who were treated with RT and 6 months of planned combined AST appear to have an increased risk of recurrence when treated with less than as compared with 6 months of the antiandrogen.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Factors

Diabetes is associated with lower risk of prostate cancer. Most men with diabetes are obese, and obesity is associated with greater prostate cancer mortality. Whether diabetes influences outcomes after prostate cancer diagnosis is unknown.. We assessed the relationship between prevalent diabetes and mortality using data from Radiation Therapy Oncology Group Protocol 92-02, a large randomized trial of men (N = 1,554) treated with radiation therapy and short-term versus long-term adjuvant goserelin for locally advanced prostate cancer. Regression and proportional hazard models were performed to evaluate relationships between prevalent diabetes and all-cause mortality, prostate cancer mortality, and non-prostate cancer mortality. Covariates included age, race, tumor stage, Gleason score, prostate-specific antigen, weight, and treatment arm.. There were a total of 765 deaths; 210 (27%) were attributed to prostate cancer. In univariate analyses, prevalent diabetes was associated with greater all-cause mortality and non-prostate cancer mortality but not prostate cancer mortality. After controlling for other covariates, prevalent diabetes remained significantly associated with greater all-cause mortality and non-prostate cancer mortality (hazard ratio [HR] = 2.12; 95% CI, 1.69 to 2.66; P < .0001) but not prostate cancer mortality (HR = 0.80; 95% CI, 0.51 to 1.25; P = .34). In contrast, weight was associated with greater prostate cancer mortality (HR = 1.77; 95% CI, 1.22 to 2.55; P = .002) but not all-cause or non-prostate cancer mortality.. Weight but not prevalent diabetes is associated with greater prostate cancer mortality in men receiving combined modality treatment for locally advanced disease. These observations suggest that the association between obesity and greater prostate cancer mortality is mediated by mechanism(s) other than the characteristic metabolic alterations of diabetes.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents, Hormonal; Diabetes Mellitus, Type 2; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Radiotherapy

Late gastrointestinal (GI) and genitourinary (GU) morbidity from external beam irradiation used to treat adenocarcinoma of the prostate continue to be a concern of physicians and patients alike. In addition, for locally advanced/high-risk cancer, the appropriate use of hormonal manipulation in addition to radiation therapy (RT) may increase toxicity. We analyzed three large Radiation Therapy Oncology Group (RTOG) studies (85-31, 86-10, and 92-02) to try to address these issues.. A total of 2,922 patients were accrued with a median follow-up of 10.3 years for surviving patients. The RTOG scoring scheme was used to assess GI, GU, and other toxicities. Toxicity reported was Grade 3 or higher late toxicity. Patient toxicity level was assessed by study and by treatment type combining RT only vs. RT + short-course hormone therapy (STH) vs. RT + long-term hormone therapy (LTH).. Multivariate analysis reveals that age >70 was statistically significantly associated with a decrease in late any Grade 3+ toxicity (hazard ratio [HR] = 0.78, p = 0.0476) adjusted for treatment type. Comparing treatment type, patients treated with RT+STH had a statistically significant lower probability of Grade 3+ GI, GU, and other toxicity compared with RT alone (p = .00006; p = 0.0037; p = 0.0127, respectively). Patients treated with RT+LTH had a statistically significant lower probability of Grade 3+ GU toxicity compared with RT alone (p = 0.023).. These data show that external beam radiation therapy remains a safe option for locally advanced/high-risk prostate cancer, and the use of hormonal manipulation does appear to be protective for GU and GI toxicity depending upon length of treatment.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Combined Modality Therapy; Flutamide; Follow-Up Studies; Gastrointestinal Tract; Goserelin; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radiation Injuries; Urogenital System

Southwest Oncology Group (SWOG) study 9921 is a randomized, phase III, intergroup study to define the role of adjuvant chemotherapy in patients with high-risk prostate cancer.. We allocated 983 patients with prostate cancer with high-risk features to receive 2 years of androgen-deprivation therapy (ADT) with or without six cycles of mitoxantrone (12 mg/m(2)) after prostatectomy.. In January 2007, SWOG 9921 was closed to further accrual after three cases of acute myelogenous leukemia (AML) were reported of a total of 487 patients in the mitoxantrone treatment arm. The key cytogenetic features of these cases included inv(16) in the first case, t(15;17) in the second, and del(5) in the third case. Time from the start of mitoxantrone to the detection of AML was 13, 48, and 72 months, respectively. Before SWOG 9921, there were no cases of mitoxantrone-induced AML reported in patients treated for prostate cancer.. The emergence of this possible pattern of secondary malignancy emphasizes the importance of randomized controlled trials in defining safety and efficacy of new approaches for patients in the adjuvant setting.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Anilides; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Fatal Outcome; Goserelin; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mitoxantrone; Nitriles; Prednisone; Prostatectomy; Prostatic Neoplasms; Risk Assessment; Risk Factors; Southwestern United States; Survival Analysis; Tosyl Compounds

To update the effect of immediate androgen suppression in conjunction with standard external-beam irradiation versus radiation alone on a group of histologically lymph node-positive patients with adenocarcinoma of the prostate.. A national prospective randomized trial (Radiation Therapy Oncology Group 85-31) of standard external-beam irradiation plus immediate androgen suppression versus external-beam irradiation alone was initiated in 1985 for patients with locally advanced adenocarcinoma of the prostate. One hundred seventy-three patients in this trial had histologically involved lymph nodes. Ninety-eight patients received radiation plus immediate androgen suppression (luteinizing hormone-releasing hormone [LHRH] agonist), whereas 75 patients received radiation alone with hormonal manipulation instituted at the time of relapse.. With a median follow-up of 6.5 years for all patients and 9.5 years for living patients, estimated progression-free survival with prostate-specific antigen (PSA) level less than 1.5 ng/mL at 5 and 9 years was 54% and 33%, respectively, for patients who received immediate LHRH agonist versus 10% [corrected] and 4% for patients who received radiation alone with hormonal manipulation instituted at time of relapse (P < .0001). Multivariate analysis revealed radiation therapy and immediate hormonal manipulation as having a statistically significant impact on all end points analyzed: absolute survival, disease-specific failure, metastatic failure, and biochemical control with PSA less than 4 ng/mL and less than 1.5 ng/mL.. Pending the results of randomized trials, patients with adenocarcinoma of the prostate who have pathologically involved pelvic lymph nodes (pathologic node-positive or clinical stage D1) should be considered for external-beam irradiation plus immediate hormonal manipulation rather than radiation alone with hormone manipulation at the time of relapse.

Topics: Adenocarcinoma; Adult; Aged; Combined Modality Therapy; Goserelin; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Prostatic Neoplasms

Androgen deprivation is an established treatment regimen for disseminated prostate cancer; however, its role in patients with localised cancer is less clear. We did a large randomised controlled trial to determine whether 3 months or 6 months of androgen deprivation given before and during radiotherapy improves outcomes for patients with locally advanced prostate cancer.. 818 men with locally advanced prostate cancer were randomly assigned to: no androgen deprivation (ie, radiotherapy alone: 66 Gy in 33 fractions of 2 Gy per day over 6.5-7.0 weeks to the prostate and seminal vesicles); 3 months' androgen deprivation with 3.6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day starting 2 months before radiotherapy (same regimen as control group); or 6 months' androgen deprivation, with the same regimen, starting 5 months before radiotherapy (same regimen as control group). Primary endpoints were time to local failure and prostate-cancer-specific survival; secondary endpoints were distant failure, disease-free survival, and freedom from salvage treatment. Analyses were done by intention to treat.. 802 (98%) patients were eligible for analysis. Median follow-up was 5.9 years (range 0.1-8.5). Compared with patients assigned no androgen deprivation, those assigned 3 months' treatment had significantly improved local failure (hazard ratio [HR] 0.56 [95% CI 0.39-0.79], p=0.001), biochemical failure-free survival (0.70 [0.56-0.88], p=0.002), disease-free survival (0.65 [0.52-0.80], p=0.0001), and freedom from salvage treatment (0.73 [0.56-0.96], p=0.025). 6 months' androgen deprivation significantly improved local failure (0.42 [0.28-0.62], p<0.0001), biochemical failure-free survival (0.58 [0.46-0.74], p<0.0001), disease-free survival (0.56 [0.45-0.69], p<0.0001), freedom from salvage treatment (0.53 [0.40-0.71], p<0.0001), distant failure (0.67 [0.45-0.99], p=0.046) and prostate-cancer-specific survival (0.56 [0.32-0.98], p=0.04) compared with no androgen deprivation.. 6 months' androgen deprivation given before and during radiotherapy improves the outlook of patients with locally advanced prostate cancer. Further follow-up is needed to estimate precisely the size of survival benefits. Increased radiation doses and additional periods of androgen deprivation might lead to further benefit.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Disease-Free Survival; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Prostatic Neoplasms

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Drug Administration Schedule; Goserelin; Humans; Injections, Intramuscular; Injections, Subcutaneous; Leuprolide; Male; Prospective Studies; Prostatic Neoplasms; Radiotherapy, Conformal; Treatment Outcome

Survival benefit in the management of high-grade clinically localized prostate cancer has been shown for 70 Gy radiation therapy combined with 3 years of androgen suppression therapy (AST), but long-term AST is associated with many adverse events.. To assess the survival benefit of 3-dimensional conformal radiation therapy (3D-CRT) alone or in combination with 6 months of AST in patients with clinically localized prostate cancer.. A prospective randomized controlled trial of 206 patients with clinically localized prostate cancer who were randomized to receive 70 Gy 3D-CRT alone (n = 104) or in combination with 6 months of AST (n = 102) from December 1, 1995, to April 15, 2001. Eligible patients included those with a prostate-specific antigen (PSA) of at least 10 ng/mL, a Gleason score of at least 7, or radiographic evidence of extraprostatic disease.. Time to PSA failure (PSA >1.0 ng/mL and increasing >0.2 ng/mL on 2 consecutive visits) and overall survival.. After a median follow-up of 4.52 years, patients randomized to receive 3D-CRT plus AST had a significantly higher survival (P =.04), lower prostate cancer-specific mortality (P =.02), and higher survival free of salvage AST (P =.002). Kaplan-Meier estimates of 5-year survival rates were 88% (95% confidence interval [CI], 80%-95%) in the 3D-CRT plus AST group vs 78% (95% CI, 68%-88%) in the 3D-CRT group. Rates of survival free of salvage AST at 5 years were 82% (95% CI, 73%-90%) in the 3D-CRT plus AST group vs 57% (95% CI, 46%-69%) in the 3D-CRT group.. The addition of 6 months of AST to 70 Gy 3D-CRT confers an overall survival benefit for patients with clinically localized prostate cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Flutamide; Goserelin; Humans; Leuprolide; Male; Middle Aged; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, Conformal; Survival Analysis

Radiation Therapy Oncology Group (RTOG) Protocol 92-02 was a randomized trial testing long-term (LT) adjuvant androgen deprivation (AD) after initial AD with external-beam radiotherapy (RT) in patients with locally advanced prostate cancer (PC; T2c-4) and with prostate-specific antigen level less than 150 ng/mL.. Patients received a total of 4 months of goserelin and flutamide, 2 months before and 2 months during RT. A radiation dose of 65 to 70 Gy was given to the prostate and a dose of 44 to 50 Gy to the pelvic lymph nodes. Patients were randomly assigned to receive no additional therapy (short-term [ST]AD-RT) or 24 months of goserelin (LTAD-RT); 1,554 patients were entered onto the study.. The LTAD-RT arm showed significant improvement in all efficacy end points except overall survival (OS; 80.0% v 78.5% at 5 years, P =.73), compared with the STAD-RT arm. In a subset of patients not part of the original study design, with tumors assigned Gleason scores of 8 to 10 by the contributing institutions, the LTAD-RT arm had significantly better OS (81.0% v 70.7%, P =.044). There was a small but significant increase in the frequency of late radiation grades 3, 4, and 5 gastrointestinal toxicity ascribed to the LTAD-RT arm (2.6% v 1.2% at 5 years, P =.037), the cause of which is not clear.. The RTOG 92-02 trial supports the addition of LT adjuvant AD to STAD with RT for T2c-4 PC. In the exploratory subset analysis of patients with Gleason scores 8 to 10, LT adjuvant AD resulted in a survival advantage.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Drug Administration Schedule; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Prognosis; Prostatic Neoplasms; Radiation Dosage; Survival Analysis; Treatment Outcome

It is known that bone mineral density (BMD) is low in men who are hypogonadal. However, the rate and sites of bone loss following testosterone deficiency are not known. The resulting hypogonadism after GnRH analog therapy for the treatment of prostate cancer allows us to examine bone loss and bone resorption immediately after testosterone withdrawal. Therefore, we examined the effects of GnRH analog treatment on bone loss and bone resorption in men with prostate cancer. BMD and serum and urine concentrations of markers of bone turnover were determined in men with prostate cancer and in age-matched controls. Measurements were taken before GnRH therapy and 6 and 12 months after instituting therapy. After 12 months of GnRH therapy, the BMD of the total hip and ultra distal radius decreased significantly (P < 0.001) in men with prostate cancer compared with the controls. The mean bone loss was 3.3% and 5.3%, respectively. The observed reduction in BMD in the spine (2.8%) and the femoral neck (2.3%) did not reach statistical significance. No significant bone loss was observed in the control subjects. The concentration of the urine marker of bone resorption, N-telopeptide, was significantly increased from baseline and from controls at both 6 and 12 months in patients treated with GnRH analog therapy compared with control subjects (P < 0.05). The concentration of a serum marker of bone formation, bone-specific alkaline phosphatase, was not significantly different from baseline or from controls at 6 and 12 months. Thus, the decreased total hip and ultra distal radius BMD and increased urinary N-telopeptide concentration after testosterone withdrawal demonstrate an increase in trabecular bone loss and enhanced bone resorption. These findings demonstrate a significant loss of bone in men with prostate cancer after receiving GnRH therapy and suggest that the total hip and radius are the preferred sites for monitoring bone loss in older men. In addition, markers of bone resorption may be helpful.

Topics: Absorptiometry, Photon; Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Bone Density; Femur Neck; Gonadotropin-Releasing Hormone; Goserelin; Humans; Hypogonadism; Male; Osteoporosis; Prospective Studies; Prostatic Neoplasms; Radius

It is unclear whether positive interactions between radiation and androgen withdrawal for patients with locally advanced prostate cancer is synergistic or additive. The present study aimed to clarify the significance of neoadjuvant androgen ablation prior to external radiotherapy in a human prostate LNCaP tumor model and in patients with locally advanced prostate cancer.. Comparisons were made between the effect of castration prior to radiation on the growth of subcutaneous LNCaP tumors implanted into male nude mice and their serum prostate-specific antigen (PSA) levels, and the results of castration or radiation alone. Twenty-nine patients with histologically proven and locally advanced adenocarcinoma of the prostate were treated with luteinizing hormone-releasing hormone analog at least 3 months before, during, and after external radiation therapy with a total dose of 70 Gy. The toxicity and response to this therapy were evaluated.. Treatment combining castration and radiation resulted in synergistic inhibition of LNCaP tumor growth and a significant delay in the emergence of androgen-independent recurrence as opposed to either treatment alone. The external radiotherapy was completed in 28 patients (96.6%), resulting in a reduction of serum PSA levels in all 28 patients to below 1.0 ng/mL. All patients were alive after a mean follow-up period of 34 months (range 11-53) with a 3-year PSA relapse-free survival rate of 83.7%. Among several factors examined, only the Gleason score was significantly associated with PSA relapse-free survival in univariate analysis, but not in multivariate analysis. Thirteen of 28 patients (46%) and 7 of 28 (25%) also showed at least one form of gastrointestinal or genitourinary toxicity, respectively. Of these patients, 8 with gastrointestinal toxicities, and 1 with genitourinary toxicity, experienced acute complications higher than grade 3.. The experimental findings objectively suggested the use of neoadjuvant androgen withdrawal prior to radiation therapy. Although our clinical experience is preliminary, combined androgen ablation and radiation therapy may also be effective in controlling locally advanced prostate cancer, with tolerable side-effects.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Animals; Antineoplastic Agents, Hormonal; Disease Models, Animal; Goserelin; Humans; In Vitro Techniques; Leuprolide; Male; Mice; Mice, Inbred BALB C; Middle Aged; Neoadjuvant Therapy; Orchiectomy; Prostatic Neoplasms; Tumor Cells, Cultured

The aim of this study was to compare the efficacy of total intermittent androgen deprivation (IAD) versus total continuous androgen deprivation (CAD) for treating patients with advanced prostate cancer in a phase III randomized trial. A total of 68 evaluable patients with hormone-naive advanced or relapsing prostate cancer were randomized to receive combined androgen blockade according to a continuous (n = 33) or intermittent (n = 35) regimen. Therapeutic monitoring was assessed by use of serum prostate-specific antigen (PSA) measurements. Patients in the CAD and IAD groups were equally stratified for age, biopsy Gleason score, and baseline serum PSA levels. The outcome variable was time to androgen-independence of the tumor, which was defined as increasing serum PSA levels despite androgen blockade. Mean follow-up was 30.8 months. The 35 IAD-treated patients completed 91 cycles, and 19 of them (54.3%) completed > or = 3 cycles. Median cycle length and percentage of time off therapy were 9.0 months and 59.5, respectively. The estimated 3-year progression rate was significantly lower in the IAD group (7.0% +/- 4.8%) than in the CAD group (38.9% +/- 11.2%, P = 0.0052). Our data suggest that IAD treatment may maintain the androgen-dependent state of advanced human prostate cancer, as assessed by PSA measurements, at least as long as CAD treatment. Further studies with longer follow-up times and larger patient cohorts are needed to determine the comparative impacts of CAD and IAD on survival.

Topics: Adenocarcinoma; Administration, Oral; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Disease Progression; Drug Administration Schedule; Flutamide; Goserelin; Humans; Injections, Subcutaneous; Male; Neoplasms, Hormone-Dependent; Prostate-Specific Antigen; Prostatic Neoplasms

To determine the effectiveness of triple androgen blockade as an alternative to watchful waiting, radical prostatectomy or radiation therapy in the management of patients with clinical stage T1 to T3 prostate cancer.. The records of 110 consecutive patients were retrospectively evaluated. Patients were treated with a three-drug androgen blockade regimen, consisting of a luteinizing hormone-releasing hormone agonist (leuprolide or goserelin) plus an antiandrogen (flutamide or bicalutamide) plus finasteride (a 5-alpha-reductase inhibitor), followed by finasteride maintenance therapy, as the sole intervention. All patients refused local therapy and had their prostates intact. Determinants of efficacy included serum prostate-specific antigen (PSA) levels and disease-specific survival.. Patients were treated for a median of 13 months with triple androgen blockade. At baseline, mean PSA level was 13.2 +/- 1.2 ng/ml (range, 0.39-100 ng/ml), and mean Gleason score was 6.6 +/- 0.1 (range, 4-10). During treatment, PSA levels declined to < or =0.1 ng/ml in all patients, with a median time of 3 months. After a median follow-up of 36 months since initiation of treatment, PSA levels have remained stable in 105 of 110 patients (95.5%). At a median follow-up of 55 months (range, 38-125 months), the mean PSA level for the first 57 patients treated in this series is 1.88 +/- 0.1 (range, 0-11.0 ng/ml). Only 9 of 110 (8.1%) patients have a PSA level > or =4.0 ng/ml. To date, no patient has received a second cycle of hormone blockade.. Although median follow-up is short, triple androgen blockade therapy followed by finasteride maintenance appears to be a promising alternative for the management of patients with clinically localized or locally advanced prostate cancer. Further study of this approach is warranted.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Finasteride; Flutamide; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoplasm Staging; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Tosyl Compounds; Treatment Outcome

Pharmacodynamics (PD), anti-tumor effects, safety and pharmacokinetics of a 3-month formulation of goserelin (Zoladex LA 10.8 mg depot: "10.8 mg depot") were investigated in a collaborative multicenter study. Study participants were 40 Japanese patients with prostate cancer comprising 20 untreated patients and 20 switch patients who had been receiving Zoladex 3.6 mg depot for 3 months or longer. Serum testosterone levels, serum LH levels, prostate-specific antigen (PSA) levels and drug concentrations were measured until 12 weeks after a single subcutaneous dose of 10.8 mg depot. Anti-tumor effects were evaluated by means of changes in the tumor lesions and the PSA levels at 12 weeks. After administration to the untreated patients, 10.8 mg depot reduced serum testosterone to the castrate range within 4 weeks and the reduction was maintained for up to 12 weeks. In the switch patients, serum testosterone suppression that had been produced by previous treatment with Zoladex 3.6 mg depot was maintained for up to 12 weeks following 10.8 mg depot administration. The anti-tumor effect at 12 weeks was 90.0% including partial response cases. The ratio of PSA normalization at 12 weeks was 75.0%. Fifty-seven adverse reactions were observed in 27 of the 40 patients (67.5%), but none were clinically significant. Although a disease flare presented as urinary retention in 1 of the untreated patients, all patients completed the study. Serum goserelin was detected up to 12 weeks after the administration of 10.8 mg depot. In conclusion a single dose of 10.8 mg depot showed a satisfactory PD-effect and brought about clinical efficacy persisting for at least 12 weeks and was well tolerated in patients with prostate cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Drug Administration Schedule; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Testosterone

To test the hypothesis that androgen ablation before and during radiotherapy for locally advanced carcinoma of the prostate may, by reducing tumor bulk and enhancing tumor cell kill, improve locoregional control and ultimately survival.. The study was conducted from 1987 to 1991. Eligible patients were those with bulky tumors (T2--T4) with or without pelvic lymph node involvement and without evidence of distant metastases. They were randomized to receive goserelin, 3.6 mg every 4 weeks; and flutamide, 250 mg t.i.d. for 2 months before radiation therapy and during radiation therapy (Arm I), or radiation therapy alone (Arm II). Of 471 randomized patients, 456 were evaluable: 226 on Arm I and 230 on Arm II.. As of November 1999, the median follow-up has reached 6.7 years for all patients and 8.6 years for alive patients. At 8 years, androgen ablation has been associated with an improvement in local control (42% vs. 30%, p = 0.016), reduction in the incidence of distant metastases (34% vs. 45%, p = 0.04), disease-free survival (33% vs. 21%, p = 0.004), biochemical disease-free survival = PSA <1.5 (24% vs. 10%, p < 0.0001), and cause-specific mortality (23% vs. 31%, p = 0.05). However, subset analysis indicates that the beneficial effect of short-term androgen ablation appears preferentially in patients with Gleason score 2--6. In that population, there is a highly significant improvement in all endpoints, including survival (70% vs. 52%, p = 0.015). In patients with Gleason 7--10 tumors, the regimen has not resulted in a significant enhancement in either locoregional control or survival.. In patients with Gleason score 2--6 carcinoma of the prostate, a short course of androgen ablation administered before and during radiotherapy has been associated with a highly significant improvement in local control, reduction in disease progression, and overall survival.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Cause of Death; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Flutamide; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Life Tables; Male; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Prostatic Neoplasms; Radiotherapy, High-Energy; Survival Analysis; Treatment Outcome

An increasingly important issue in the management of prostate cancer is the occurrence of biochemical failure (ie, increasing serum prostate-specific antigen [PSA] levels) in patients with clinically localized prostate cancer who initially underwent definitive treatments with curative intent (prostatectomy and/or radiation therapy). This pilot trial evaluated chemotherapy followed by hormone therapy for a defined period in patients with biochemical (and possibly clinical) recurrence after initial local therapies for localized/locally advanced prostate cancer. Patients who developed increasing PSA > 4 ng/mL after initial prostatectomy and/or radiation therapy received docetaxel, 70 mg/m(2) every 3 weeks for up to 6 courses, followed by 4 months of total androgen suppression (using a luteinizing hormone-releasing hormone agonist plus bicalutamide, 50 mg/d) and 8 months of peripheral androgen blockade (using finasteride, 5 mg/d, plus bicalutamide, 50 mg/d). Twenty-seven patients have enrolled to date, 23 of whom received four or six cycles of docetaxel before hormonal therapies. Seventeen (74%) of 23 patients who completed four to six cycles of chemotherapy had a > or =40% decrease in PSA, and 16 (89%) of 18 patients who completed 4 months of total androgen suppression achieved PSA values of < or =0.1. The most common hematologic toxicity was grade (3/4) neutropenia; grade 3 nonhematologic toxicities were rare, and no grade 4 nonhematologic toxicities were reported. Thus, the preliminary results suggest that docetaxel before hormonal therapy includes a PSA response in many prostate cancer patients with biochemical failure after definitive local therapies.

Topics: Adenocarcinoma; Aged; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Docetaxel; Finasteride; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoplasm Recurrence, Local; Nitriles; Paclitaxel; Pilot Projects; Prostate-Specific Antigen; Prostatic Neoplasms; Salvage Therapy; Taxoids; Tosyl Compounds

The likelihood of finding organ-confined untreated prostate cancer (PCa) by pathological examination at the time of radical prostatectomy (RP) is only 50% in patients with clinically organ-confined disease. In addition, tumour is present at the resection margin in approximately 30% of clinical T2 (clinical stage B) cases. The issue of clinical "understaging" and of resection limit positivity have led to the development of novel management practices, including "neoadjuvant" hormonal therapy (NHT). The optimal duration of NHT is unknown. We undertook the present analysis to evaluate the effect of NHT on pathologic stage of PCa and resection limit status in patients with prostate cancer and treated with total androgen ablation either for three or six months before RP. Between January 1996 and February 1998, 259 men with prostate cancer underwent radical retropubic prostatectomy and bilateral pelvic node dissection in the 26 centres participating in the Italian randomised prospective PROSIT study. Whole mount sectioning of the complete RP specimens was adopted in each centre for accurately evaluating the pathologic stage and resection limit status. By February 1998, haematoxylin and eosin stained sections from 155 RP specimens had been received and evaluated by the reviewing pathologist (RM). 64 cases had not been treated with total androgen ablation (e.g. NHT) before RP was performed, whereas 58 and 33 had been treated for three and six months, respectively. 114 patients were clinical stage B whereas 41 were clinical stage C. After three months of total androgen ablation, pathological stage B was more prevalent among patients with clinical B tumours, compared with untreated patients (57% in treated patients vs. 36% in untreated). The percentage of cancers with negative margins was statistically significantly greater in patients treated with neoadjuvant therapy than those treated with immediate surgery alone (69% vs. 42%, respectively). After six months of NHT therapy the proportion of patients with pathological stage B (67% vs. 36%, respectively) and negative margins was greater than after 3 months (92% vs. 42%, respectively). For clinical C tumours, the prevalence of pathological stage B and negative margins in the patients treated for either 3 or 6 months was not as high as in the clinical B tumours, when compared with the untreated group (pathological stage B: 31% and 33% vs. 6% in the clinical C cases, respectively. Negative margins: 56% and 67% vs. 31%,

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Nitriles; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Time Factors; Tosyl Compounds; Treatment Outcome

Black race has been associated with a significantly increased risk of prostate cancer mortality. This exploratory analysis investigated the effect of race on the clinical outcome of combined androgen blockade (CAB).. Data for analysis were obtained from a double-blind, randomized, multicenter trial comparing CAB in the form of bicalutamide (50 mg once daily) or flutamide (250 mg three times daily) plus luteinizing hormone-releasing hormone analogs (LHRHa; goserelin acetate 3.6 mg, or leuprolide acetate 7.5 mg) in 813 patients with stage D(2) prostate cancer (median follow-up, 160 weeks). Patients were analyzed according to race (African American [AA], white, or other). The primary clinical events were disease progression and survival.. Four hundred and four patients received bicalutamide/LHRHa and 409 received flutamide/LHRHa. Although treatment with bicalutamide/LHRHa resulted in slightly longer time to progression and survival time in white and AA males than treatment with flutamide/LHRHa, the differences between the treatment groups were not statistically significant.. No marked effect of race on clinical outcome was observed regardless of antiandrogen, suggesting that similar treatment benefits are to be expected in either race.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Black People; Bone Neoplasms; Cohort Studies; Disease Progression; Disease-Free Survival; Double-Blind Method; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Nitriles; Prostatic Neoplasms; Tosyl Compounds; White People

To evaluate the effect of immediate androgen suppression in conjunction with standard external beam irradiation (RT) versus RT alone on a group of men after prostatectomy who had indications for adjuvant treatment.. A national prospective randomized trial (Radiation Therapy Oncology Group [RTOG] 85-31) comparing standard external beam RT plus immediate androgen suppression versus external beam RT alone with delayed hormonal treatment at relapse was initiated for patients with locally advanced adenocarcinoma of the prostate. One hundred thirty-nine of the patients in this trial had indications for adjuvant treatment after prostatectomy (eg, capsular penetration, seminal vesicle involvement). Seventy-one of the patients received RT with immediate androgen suppression (luteinizing hormone-releasing hormone [LHRH] agonist); 68 patients received RT alone with hormonal manipulation instituted only at the time of relapse.. With a median follow-up of 5 years, the estimated progression-free survival rate (failure defined as prostate-specific antigen [PSA] greater than 0.5 ng/mL) was 65% for the men who received combination therapy and 42% for those treated by RT alone with hormones reserved for relapse (P = 0.002). Differences in the rates of freedom from biochemical relapse were observed when failure was defined as PSA of 1.0 to 3.9 ng/mL (71% versus 46%; P = 0.008) and PSA greater than 4.0 ng/mL (76% versus 55%; P = 0.05), respectively. No differences were observed between the groups with respect to the end points of local control, distant failure, and overall survival. The use of immediate androgen suppression (ie, LHRH agonists) and the absence of pathologic nodal involvement were independently associated with prolongation of freedom from biochemical relapse by multivariate analysis.. Patients with prostate cancer and indications for postoperative RT should be considered for combined RT and hormonal manipulation. Because statistically significant advantages for this experimental approach could not be defined for all end points studied (in particular, overall survival), efforts should be made to enroll these patients in the recently activated RTOG trial (96-01) comparing RT plus placebo to the combination of RT plus Casodex in the postoperative setting.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Disease-Free Survival; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms

Although androgen suppression results in a tumor response/remission in the majority of patients with carcinoma of the prostate, its potential value as an adjuvant has not been substantiated.. In 1987, the Radiation Therapy Oncology Group (RTOG) initiated a randomized phase III trial of adjuvant goserelin in definitively irradiated patients with carcinoma of the prostate. A total of 977 patients had been accessioned to the study. Of these, 945 remained analyzable: 477 on the adjuvant arm and 468 on the observation arm.. Actuarial projections show that at 5 years, 84% of patients on the adjuvant goserelin arm and 71% on the observation arm remain without evidence of local recurrence (P < .0001). The corresponding figures for freedom from distant metastases and disease-free survival are 83% versus 70% (P < .001) and 60% and 44% (P < .0001). If prostate-specific antigen (PSA) level greater than 1.5 ng is included as a failure (after > or = 1 year), the 5-year disease-free survival rate on the adjuvant goserelin arm is 53% versus 20% on the observation arm (P < .0001). The 5-year survival rate (for the entire population) is 75% on the adjuvant arm versus 71% on the observation arm (P = .52). However, in patients with centrally reviewed tumors with a Gleason score of 8 to 10, the difference in actuarial 5-year survival (66% on the adjuvant goserelin arm v 55% on the observation arm) reaches statistical significance (P = .03).. Application of androgen suppression as an adjuvant to definitive radiotherapy has been associated with a highly significant improvement in local control and freedom from disease progression. At this point, with a median follow-up time of 4.5 years, a significant improvement in survival has been observed only in patients with centrally reviewed tumors with a Gleason score of 8 to 10.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Follow-Up Studies; Goserelin; Humans; Male; Prognosis; Prostatic Neoplasms; Survival Analysis

The present study evaluated serial serum measurements of tissue polypeptide-specific antigen (TPS) in comparison with prostate-specific antigen (PSA) for assessment of tumour progression in patients with advanced prostate cancer receiving intermittent androgen suppression therapy (IAS). Twenty-three men were recruited into an IAS trial consisting of an initial 8 months of androgen suppression, followed by cycles of treatment cessation and resumption of therapy upon increases of PSA > 20 ng ml(-1) to prolong the hormone responsiveness of the tumour cells. Periods of androgen suppression resulted in reversible reduction in serum testosterone (< 1.8 nmol I(-1)) and PSA (< 4 ng ml(-1)) and decreases in tumour volume (mean reduction for first cycle 24 +/- 10%), indicating partial growth arrest and apoptotic regression of the tumours. In contrast to PSA values, non-specifically elevated TPS values were found in 8 of 23 patients. In 15 of 23 patients, TPS fell during periods of apoptotic tumour regression and increased simultaneously with testosterone and preceded the increases in PSA by 2 months during the period of treatment cessation. Although TPS represents a highly sensitive marker of tumour proliferation in this IAS clinical model of controlled tumour regression and regrowth, its low specificity compared with PSA limits its usefulness to monitoring of prostate cancer patients with proven absence of non-specific elevations of this marker.

Topics: Adenocarcinoma; Androgen Antagonists; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cyproterone Acetate; Drug Administration Schedule; Goserelin; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Tissue Polypeptide Antigen

We conducted a randomized, prospective trial comparing external irradiation with external irradiation plus goserelin (an agonist analogue of gonadotropin-releasing hormone that reduces testosterone secretion) in patients with locally advanced prostate cancer.. From 1987 to 1995, 415 patients with locally advanced prostate cancer were randomly assigned to receive radiotherapy alone or radiotherapy plus immediate treatment with goserelin. The patients had a median age of 71 years (range, 51 to 80). Patients in both groups received 50 Gy of radiation to the pelvis over a period of five weeks and an additional 20 Gy over an additional two weeks as a prostatic boost. Patients in the combined-treatment group received 3.6 mg of goserelin (Zoladex) subcutaneously every four weeks starting on the first day of irradiation and continuing for three years; those patients also received cyproterone acetate (150 mg orally per day) during the first month of treatment to inhibit the transient rise in testosterone associated with the administration of goserelin.. Data were available for analysis on 401 patients. The median follow-up was 45 months. Kaplan-Meier estimates of overall survival at five years were 79 percent (95 percent confidence interval, 72 to 86 percent) in the combined-treatment group and 62 percent (95 percent confidence interval, 52 to 72 percent) in the radiotherapy group (P=0.001). The proportion of surviving patients who were free of disease at five years was 85 percent (95 percent confidence interval, 78 to 92 percent) in the combined-treatment group and 48 percent (95 percent confidence interval, 38 to 58 percent) in the radiotherapy group (P<0.001).. Adjuvant treatment with goserelin, when started simultaneously with external irradiation, improves local control and survival in patients with locally advanced prostate cancer.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Cyproterone Acetate; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms; Survival Analysis; Treatment Outcome

We determined whether 12 weeks of neoadjuvant testicular androgen ablation therapy using a luteinizing hormone-releasing hormone agonist could improve pathological outcomes in men undergoing radical retropubic prostatectomy for clinically localized (stages T1C, T2A and T2B) prostatic carcinoma.. A total of 56 participants was randomized to receive either monthly injections of a luteinizing hormone-releasing hormone agonist at 4-week intervals followed by radical retropubic prostatectomy (28) or to undergo immediate radical retropubic prostatectomy alone (28). Operations were performed via similar technique and all prostatic specimens were processed histologically in their entirety.. There was no improvement in pathological outcome using luteinizing hormone-releasing hormone agonist preoperatively compared to surgery alone. Of 28 men undergoing immediate radical retropubic prostatectomy 23 had organ-confined (17) or specimen-confined (6) disease versus 22 of 28 who received luteinizing hormone-releasing hormone neoadjuvant therapy for 12 weeks preoperatively (16 with organ-confined and 6 with specimen-confined disease, p = 1.00). In addition, when the study population was analyzed by pretreatment prostate specific antigen (PSA) levels (10 ng./ml. or less, or greater than 10 ng./ml/) there was also no difference in pathological outcome (p = 0.65 for PSA greater than 10 and p = 0.32 for PSA less than 10).. Neoadjuvant androgen ablation therapy for 12 weeks before radical prostatectomy in patients with clinically localized adenocarcinoma of the prostate does not result in improved pathological outcomes.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Combined Modality Therapy; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Prostatectomy; Prostatic Neoplasms; Treatment Outcome

A prospective randomised study was performed to test the hypothesis that total androgen ablation, achieved by combining an LHRH analogue, goserelin acetate (Zoladex), with an antiandrogen, cyproterone acetate (Cyprostat), is more effective than conventional monotherapy in delaying the time to progression of metastatic prostatic cancer. 525 patients were recruited at 18 UK centres between May 1986 and January 1989, 175 patients being allocated to each arm. Patients were clinically and biochemically assessed at 1, 2, 3, 6, 9 and 12 months after initiation of therapy and then every 6 months until a maximum duration of 48 months. There was no statistically significant difference in terms of median time to progression between the combination treatment arm and either monotherapy arm, although there was a statistically significant difference between goserelin acetate alone and cyproterone acetate alone, in favour of goserelin acetate (p = 0.016). All treatment regimens were well tolerated and cyproterone acetate reduced both tumour flare reactions and hot flushes in patients receiving goserelin acetate. It is concluded that total androgen ablation using cyproterone acetate (300 mg/day) and goserelin acetate (3.6 mg every 28 days) confers no advantage in terms of time to progression, to conventional monotherapy, but can reduce certain side effects caused by LHRH analogue treatment alone.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cyproterone Acetate; Disease Progression; Goserelin; Humans; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Safety

A randomized, multicenter trial, double-blind for antiandrogen therapy, compared the antiandrogens bicalutamide and flutamide, each combined with luteinizing hormone-releasing hormone analogue therapy (LHRH-A) in 813 patients with Stage D2 prostate carcinoma. An analysis of time to progression (median follow-up, 95 weeks) was performed to augment previous analyses of time to treatment failure and time to death.. Patients were randomly assigned 1:1 to double-blind antiandrogen therapy, receiving either bicalutamide (50 mg once daily) or flutamide (250 mg three times daily), and were assigned 2:1 to LHRH-A with goserelin acetate (3.6 mg every 28 days) or leuprolide acetate (7.5 mg every 28 days). The primary endpoint of the trial was time to treatment failure, defined as an adverse event leading to withdrawal of randomized therapy, objective progression, death, or withdrawal from study therapy for any reason. Secondary endpoints were time to death, quality of life, and subjective response. The current analysis of time to progression included progression data collected prospectively for 561 patients (69%) and retrospectively for 252 patients (31%).. Disease progression occurred for 223 of 404 patients (55%) in the bicalutamide plus LHRH-A group and for 235 of 409 patients (58%) in the flutamide plus LHRH-A group. The hazard ratio for time to progression of bicalutamide plus LHRH-A to that of flutamide plus LHRH-A was 0.9 (two-sided 95% confidence interval [CI], 0.75 to 1.08; P = 0.26). The upper one-sided 95% CI was 1.05, which met the definition of equivalence (< 1.25).. At a median follow-up time of 95 weeks, bicalutamide plus LHRH-A and flutamide plus LHRH-A had equivalent time to progression.

Topics: Adenocarcinoma; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Double-Blind Method; Flutamide; Goserelin; Humans; Leuprolide; Male; Nitriles; Prostatic Neoplasms; Tosyl Compounds

To compare the efficacy and safety of bicalutamide and flutamide, each used in combination with luteinizing hormone-releasing analogue (LHRH-A) therapy, in patients with untreated metastatic (Stage D2) prostate cancer.. Randomized, double-blind (for antiandrogen therapy), multicenter study with a 2 x 2 factorial design. Eight hundred thirteen patients were allocated 1:1 to bicalutamide (50 mg once daily) and flutamide (250 mg three times daily) and 2:1 to goserelin acetate (3.6 mg every 28 days) and leuprolide acetate (7.5 mg every 28 days).. With a median duration of follow-up of 49 weeks, time to treatment failure, the primary endpoint, was significantly (P = 0.005) better for the bicalutamide plus LHRH-A group than for the flutamide plus LHRH-A group. Patients in the flutamide plus LHRH-A group were 34% more likely to fail treatment over the given time period, as indicated by the hazard ratio of 0.749 (95% confidence interval, 0.61 to 0.92) for bicalutamide plus LHRH-A to flutamide plus LHRH-A. Results for secondary endpoints (survival, quality of life, and subjective response) were similar between groups. Diarrhea occurred in 24% of patients in the flutamide plus LHRH-A group, compared with 10% of patients in the bicalutamide plus LHRH-A group (P < 0.001).. In patients with metastatic prostate cancer, bicalutamide plus LHRH-A is well tolerated and provides superior efficacy to flutamide plus LHRH-A with respect to time to treatment failure. Assessment of the effects of these regimens on longer term survival requires additional time for follow-up.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Anilides; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Confidence Intervals; Double-Blind Method; Flutamide; Follow-Up Studies; Goserelin; Humans; Leuprolide; Male; Middle Aged; Nitriles; Proportional Hazards Models; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Regression Analysis; Survival Rate; Tosyl Compounds; Treatment Failure

Androgen deprivation therapy before and during radiation therapy could, by reducing tumor volume, increase local tumor control, disease-free survival, and overall survival in patients with locally advanced adenocarcinomas of the prostate.. In a randomized controlled clinical trial, patients with large T2, T3, and T4 prostate tumors, but no evidence of osseous metastasis, were randomized to receive goserelin 3.6 mg subcutaneously every 4 weeks and flutamide 250 mg orally three times daily 2 months before and during the radiation therapy course (Arm I) compared with radiation therapy alone (Arm II). Pelvic irradiation was administered with 1.8 to 2.0 Gy per day to a total dose of 45 +/- 1 Gy followed by a boost to the prostate target volume to a total dose of 65 to 70 Gy.. Of 471 randomized patients, 456 were evaluable, 226 on Arm I and 230 on Arm II. With a median potential follow-up of 4.5 years, the cumulative incidence of local progression at 5 years was 46% in Arm I and 71% in Arm II (P < 0.001). The 5-year incidence of distant metastasis on Arms I and II was 34% and 41%, respectively (P = 0.09). Progression-free survival rates including normal prostate-specific antigen (PSA) levels for 396 patients with at least one PSA recorded were 36% in Arm I and 15% in Arm II at 5 years (P < 0.001). At this time, no significant difference in overall survival could be detected (P = 0.7).. Short-term androgen deprivation with radiation therapy results in a marked increase in local control and disease-free survival compared with pelvic irradiation alone in patients with locally advanced carcinoma of the prostate. Long-term surveillance is required to assess effects on overall survival.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Combined Modality Therapy; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms

To eliminate the initial testosterone (T) surge and prevent the risk of flare-up induced by the first administration of luteinizing hormone-releasing hormone (LH-RH) analogue, we examined the effectiveness of short-term combination therapy with diethylstilbestrol (DES). Sixteen previously untreated patients with prostate carcinoma (Stage C: 4 cases, Stage D2: 12 cases) were randomly assigned to 4 groups. Each group included 4 patients. Group 1 received DES (500 mg daily injection) for 7 days, staring before the first subcutaneous injection of luteinizing hormone releasing hormone (LH-RH) analogue (3.6 mg of Zoladex depot); Group 2 received 500 mg of DES injection for 7 days prior to the initiation of therapy with the LH-RH analogue, and moreover received a DES injection for 7 days; Group 3 received 500 mg of DES injection for 7 days simultaneously with the first injection of the LH-RH analogue; Group 4 was pretreated with 500 mg of DES injection for 7 days prior to the initiation of therapy with the LH-RH analogue, with additional DES injection for 3 days. In groups 1, 2 and 4 the level of T decreased during the 7 days of DES therapy, and at 3 days after the first injection of LH-RH analogue increased again. The mean T value in groups 1, 2 and 4 decreased by 33.2 +/- 27.6% (mean +/- SE), 20.5 +/- 20.8%, 13.2 +/- 9.8%, respectively, at the day of the first injection of LH-RH analogue, and increased by 75.2 +/- 21.6%, 70.7 +/- 63.4%, 56.7 +/- 46.4%, respectively, at 3 days after the first injection of LH-RH analogue.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Diethylstilbestrol; Drug Administration Schedule; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Testosterone

Neoadjuvant total androgen ablation therapy leads to involutional changes in prostatic carcinoma and may have the potential to downstage operable prostate cancers. We studied 27 clinically localized prostatic carcinomas after 3 months of combined treatment with a luteinizing hormone-releasing hormone agonist, goserelin acetate, and the antiandrogen flutamide, followed by radical retropubic prostatectomy, for changes in the serum prostate-specific antigen (PSA) level, changes in prostatic volume, therapy-induced histopathologic changes, DNA ploidy, and proliferative activity. Ten hormonally untreated, grade-matched prostatic adenocarcinomas served as controls. The mean pretherapy serum PSA level was 17.5 ng/ml, and posttherapy PSA levels were all < 4.0 ng/ml, with 18 men having undetectable levels. The mean reduction in prostatic volume following hormonal therapy was 37% (range 16-52%). Pathologic staging confirmed 20 pT2N0, six pT3N0, and one pT3N1. All prostates showed residual adenocarcinoma (extremely focal in seven cases [26%] with loss of glandular architecture, cytoplasmic vacuolization, and nuclear pyknosis. High-grade adenocarcinoma was nondiploid in 25% of hormonally treated prostates and 80% of 10 untreated controls. Immunostaining for proliferating cell nuclear antigen showed > 10% nuclear reactivity in 33% of treated carcinomas and 90% of untreated carcinomas. In conclusion, 3 months of neoadjuvant androgen ablation for localized prostatic carcinoma significantly lowers serum PSA and prostatic volume and produces involutional changes in residual carcinomas that mimic high-grade disease. However, pretreated carcinomas have predominantly a diploid DNA content and low proliferative activity as opposed to untreated carcinomas. Thus, grading of pretreated adenocarcinomas by conventional methods may be misleading. Preoperative total androgen ablation has a profound effect on a subset of prostatic carcinoma cells, possibly by facilitating programmed cell death.

Topics: Adenocarcinoma; Cell Division; Combined Modality Therapy; Diploidy; Flutamide; Goserelin; Humans; Male; Neoplasm Staging; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

To determine if initial chemo-hormone therapy (estramustine phosphate) of metastatic prostate carcinomas can lengthen the period until progression, compared with hormone treatment (goserelin) alone? The time to progression, side effects and prognostic factors were assessed.. The prospective phase III study (II 86 until V 91) involved 243 patients randomized consecutively in two groups. Progress was assessed according to NPCP criteria.. The following prognostic factors were established to be significant: metastatic status, metastatic bone pain, alkaline phosphatase and performance status. No difference was observed between the two methods of treatment in time to progression. However on stratifying according to groups with the same prognostic factors, progression in the high risk group occurred at a later stage during treatment with estramustine than during pure hormone treatment. The quality of life was clearly more heavily restricted by side effects from estramustine.. Thus, when comparing these treatments, there were no statistically significant differences. Patients in the high risk groups with unfavorable prognosis factors benefitted from the chemo-hormone treatment with estramustine phosphate.

Topics: Adenocarcinoma; Aged; Estramustine; Goserelin; Humans; Male; Prognosis; Prospective Studies; Prostatic Neoplasms; Risk Factors; Time Factors

Eighteen consecutive patients with measurable locally advanced or metastatic pancreatic adenocarcinoma were treated with goserelin (Zoladex) 3.6 mg subcutaneously every 4 weeks. Hydrocortisone 20 milligrams twice daily was commenced with the second injection of goserelin. Objective tumour response was monitored by computerised tomography of the abdomen. There was no objective remission in disease sites. Serial measurements of serum tumour markers showed no reduction in serum CA 19-9 and CA 195 concentrations. The median duration of survival of all cases was 5 months. Administration of goserelin resulted in significant reductions in oestradiol, testosterone, androstenedione in males and reductions in FSH and LH in both males and females. The addition of hydrocortisone resulted in further reductions of androstenedione and testosterone levels in males. Thus goserelin showed no anti-tumour effect, but concentrations required for direct inhibitory effects may be higher than those required to produce effects on hormone suppression.

Topics: Adenocarcinoma; Adult; Aged; Androgens; Androstenedione; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Hydrocortisone; Luteinizing Hormone; Male; Middle Aged; Pancreatic Neoplasms; Testosterone

Topics: Adenocarcinoma; Drug Therapy, Combination; Flutamide; Goserelin; Humans; Male; Neoplasm Staging; Orchiectomy; Patient Satisfaction; Prostatic Neoplasms; Survival Rate

We report preliminary results for the first 164 patients enrolled in a multicenter study comparing the endocrine effects, efficacy, and safety of 3.6 mg of goserelin acetate (Zoladex) and orchiectomy in patients with Stage D2 prostate cancer. Eighty-one patients were randomly allocated to receive Zoladex and 83 to orchiectomy. The median follow-up time for all patients was two hundred ten days. Median serum levels of testosterone were reduced to castrate levels (less than 50 ng/dL) within four weeks in both groups and remained suppressed for up to sixty weeks. An objective response according to modified criteria of the National Prostatic Cancer Project was observed in 81 percent and 78 percent of patients in the Zoladex and orchiectomy groups, respectively. There were no statistically significant differences between treatment groups in the distributions of time to treatment failure or time to disease progression. The most commonly reported adverse events in both treatment groups were hot flashes, cancer-related pain, unspecified pain, and urinary symptoms. These results suggest that Zoladex may offer an alternative to orchiectomy in the treatment of advanced prostate cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Buserelin; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Orchiectomy; Prospective Studies; Prostatic Neoplasms; Testosterone

Topics: Adenocarcinoma; Buserelin; Clinical Trials as Topic; Delayed-Action Preparations; Goserelin; Humans; Injections, Subcutaneous; Interleukin-2; Male; Orchiectomy; Prostatic Neoplasms; Random Allocation; Recombinant Proteins

Twenty-seven patients with metastatic adenocarcinoma of the prostate were treated with the new luteinizing hormone-releasing hormone analog, Zoladex (ICI 118,630) for up to ninety-eight weeks. Initially, treatment was randomized between Zoladex 250 micrograms and 500 micrograms self-injected subcutaneously every day for a minimum period of twelve weeks following which a sustained-release, once-monthly depot formulation of Zoladex 3.6 mg s.c. was used. Acute rises in serum gonadotropins and testosterone during the first two days were followed by declines in hormone levels over the following three weeks. Median time to castration with 500 micrograms/day was twenty-two days compared with forty-three days with 250 micrograms/day (p = 0.06). No significant endocrinologic changes occurred during the transfer to the depot, and serum testosterone remained 95 per cent suppressed throughout the duration of the study. After three months the median daily serum Zoladex concentrations ranged between 0.47 and 0.53 ng/ml and were not significantly different among the three dosage forms. No specific correlation among serum Zoladex concentrations, endocrinologic parameters, and tumor response rates were found. Hot flashes initially, and decreased libido were the only common complaints. Zoladex was well tolerated, and no side effects required dose-modification or removal from the study. Tumor response rates up to one year appeared to be comparable to the conventional endocrine therapies. This analog in monthly depot formulation is recommended for further clinical evaluation.

Topics: Adenocarcinoma; Buserelin; Clinical Trials as Topic; Delayed-Action Preparations; Goserelin; Humans; Injections, Subcutaneous; Male; Prostatic Neoplasms; Random Allocation; Time Factors

Zoladex, a sustained-release luteinizing hormone--releasing hormone (LHRH) analogue administered by subcutaneous injection every 28 days, was evaluated at three dose levels in 46 men with untreated advanced prostate cancer. All three Zoladex doses yielded similar endocrinologic effects. After initial transient increases in serum luteinizing hormone, follicle-stimulating hormone, and testosterone concentrations, serum testosterone was suppressed uniformly to castration levels within 22 days. At a median follow-up of 41 weeks, Zoladex had maintained persistent suppression of serum testosterone. Measurements of serum Zoladex levels indicated that release of the drug from the injected depot was sustained over a period of 1 month and that there was no drug accumulation as evaluated over an initial 3-month period. No antibodies to Zoladex were detected. Tumor regression rates and side effects with Zoladex therapy were similar to those reported with daily injections of subcutaneous LHRH therapy. Signs and symptoms consistent with a brief tumor flare after the first injection of the LHRH analogue were noted in eight (17%) of the study entrants. Spinal cord compression was observed in two patients within 1 week from the onset of therapy. Zoladex is considered to be an effective, sustained-release LHRH analogue for the treatment of patients with prostate cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Buserelin; Delayed-Action Preparations; Drug Evaluation; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Statistics as Topic; Testosterone

Between April, 1984 and March, 1985 in 14 centers, 33 patients with prostatic cancer of our 14 centers were randomized to subcutaneously receive either 125, 250, or 500 micrograms/day of ICI 118,630, an LH-RH analogue, for 12 weeks, and the clinical efficacy, safety and endocrinal effects of the drug by dose were examined. An objective partial response was obtained in 44.4% of the 125 micrograms-treated group, in 50.0% of the 250 micrograms-treated group, and 42.9% of the 500 micrograms-treated group, showing no significant difference between the groups. General subjective response rates in these three groups were respectively 75.0%, 62.5%, and 85.7%, not differing from each other significantly. No significant difference was observed in endocrinal effect which was seen in 58.3%, 66.7%, and 100% of 125 micrograms, 250 micrograms, and 500 micrograms groups, respectively. Medical castration was attained in 4.1 +/- 2.0 weeks on average. Adverse reactions observed included fever up to 37 degrees C in 1 of the 13 (7.3%) patients treated with 125 micrograms, and hot feeling at the injection site and flare in 1 of the 8 (12.5%) patients treated with 500 micrograms, which were all mild. These patients responded to further ICI 118,630 therapy without requiring any treatment for the adverse reactions.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Buserelin; Drug Evaluation; Gonadotropins, Pituitary; Goserelin; Humans; Injections, Subcutaneous; Male; Middle Aged; Prostatic Neoplasms; Random Allocation

We report the failure to achieve castrate level of serum testosterone during luteinizing hormone-releasing hormone agonist therapy in a patient with prostate cancer. A 76-year-old man was admitted to our hospital for evaluation of an elevated serum prostate specific antigen (PSA) level (191.10 ng/ml) in August 2011. He was diagnosed with T3aN0M1b prostate adenocarcinoma. A combined androgen blockade using luteinizing hormone-releasing hormone agonist (the 1-month depot of leuprorelin acetate) and antiandrogen was administered. Due to liver dysfunction, antiandrogens, both bicalutamide and flutamide, were stopped. The 1-month depot was switched to the 3-month depot in May 2013, but the patient complained of induration and abscess at the infection site. Leuprorelin acetate was replaced by goserelin acetate. Because no adverse event appeared after injection of the 1-month depot of goserelin acetate, the 3-month depot was administered in October 2013. The PSA level increased gradually, and the testosterone level was greater than 50 ng/dl, that is, above castrate range. The 3-month depot of both leuprorelin acetate and goserelin acetate was not effective for this patient. For this reason, the 1-month depot of leuprorelin acetate was started resulting in a rapid decrease in PSA and testosterone levels. Thereafter, androgen depriving therapy could be continued. Androgen deprivation therapy is the standard treatment for patients with advanced prostate cancer and luteinizing hormone-releasing hormone aims to suppress serum testosterone to castrate range. We recommend assessing the serum testosterone levels during luteinizing hormone-releasing hormone agonist therapy for monitoring treatment efficacy and verifying progression when the PSA level increases.

Topics: Adenocarcinoma; Aged; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Gonadotropin-Releasing Hormone; Goserelin; Humans; Kallikreins; Leuprolide; Male; Nitriles; Phenylthiohydantoin; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Testosterone; Tosyl Compounds

Topics: Adenocarcinoma; Aged, 80 and over; Anilides; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Combined Modality Therapy; Fatal Outcome; Goserelin; Humans; Lymphatic Metastasis; Male; Nitriles; Prostatic Neoplasms; Skin Neoplasms; Skin Ulcer; Tosyl Compounds; Transurethral Resection of Prostate

Topics: Adenocarcinoma; Aged, 80 and over; Alopecia; Anilides; Antineoplastic Combined Chemotherapy Protocols; Atrophy; Fibrosis; Goserelin; Humans; Male; Nitriles; Prostatic Neoplasms; Scalp; Skin; Tosyl Compounds

of this study is to determine the temporal resolution of therapy-induced pneumonitis, and to assess promoting factors in adjuvant treated patients with unilateral mammacarcinoma.. A total of 100 post-surgery patients were recruited. The cohort was treated by 2 field radiotherapy (2FRT; breast and chest wall, N = 75), 3 field radiotherapy (3FRT; + supraclavicular lymphatic region, N = 8), or with 4 field radiotherapy (4FRT; + parasternal lymphatic region, N = 17). Ninety-one patients received various systemic treatments prior to irradiation. Following an initial screening visit post-RT, two additional visits after 12 and 25 weeks were conducted including radiographic examination. In addition, general anamnesis and the co-medication were recorded. The endpoint was reached as soon as a pneumonitis was developed or at maximum of six months post-treatment.. A pneumonitis incidence of 13% was determined. Of 91 patients with prior systemic therapy, 11 patients developed pneumonitis. Smoking history and chronic obstructive pulmonary disease (COPD) appeared to be positive predictors, whereas past pneumonia clearly promoted pneumonitis. Further pneumonitis-promoting predictors are represented by the applied field extensions (2 field radiotherapy [2FRT] < 3 field radiotherapy [3FRT] < 4 field radiotherapy [4FRT]) and the type of combined initial systemic therapies. As a consequence, all of the three patients in the study cohort treated with 4FRT and initial chemotherapy combined with anti-hormone and antibody protocols developed pneumonitis. A combination of the hormone antagonists tamoxifen and goserelin might enhance the risk for pneumonitis. Remarkably, none of the 11 patients co-medicated with statins suffered from pneumonitis.. The rapidly increasing use of novel systemic therapy schedules combined with radiotherapy (RT) needs more prospective studies with larger cohorts. Our results indicate that contribution to pneumonitis occurrence of various (neo)adjuvant therapy approaches followed by RT is of minor relevance, whereas mean total lung doses of >10 Gy escalate the risk of lung tissue complications. The validity of potential inhibitors of therapy-induced pneumonitis as observed for statin co-medication should further be investigated in future trials.

Topics: Adenocarcinoma; Adult; Aged; Breast Neoplasms; Carcinoma in Situ; Chemotherapy, Adjuvant; Cohort Studies; Female; Goserelin; Humans; Incidence; Mastectomy; Middle Aged; Prospective Studies; Radiation Pneumonitis; Radiotherapy, Adjuvant; Risk Factors; Tamoxifen

Immunohistochemical and morphometric analysis of the microcirculatory bed in the tumor and non-tumor parenchyma of the prostate was carried out with the use of endothelial cell marker CD34 in patients treated by high-intensity focused ultrasound (HIFU). The numerical density of microvessels in the adenocarcinoma focus did not correlate with the degree of its differentiation, while high values of this parameter were associated with lower incidence of local progression after HIFU. Effective HIFU ablation led to progressive fibrosis and significant reduction of the microcirculatory bed in zones of intact non-tumor glands in control samples; an inverse relationship between the degree of reduction of the microcirculatory bed and the probability of relapse was revealed. The use of HIFU in combination with androgen deprivation was associated with a decrease in numerical density of microvessels in zones of tumor and non-tumor parenchyma in patients with relapses.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Antigens, CD34; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Fibrosis; Flutamide; Follow-Up Studies; Goserelin; High-Intensity Focused Ultrasound Ablation; Humans; Male; Microcirculation; Middle Aged; Prognosis; Prostate; Prostatic Neoplasms; Treatment Outcome; Tumor Microenvironment

Although treatment options for men with metastatic castrate-resistant prostate cancer have improved in recent years, the outlook for patients remains poor, with overall survival in the region of 2 years. Response rates with chemotherapy are modest and disease progression is usually observed within months of stopping treatment.. We present a case of a 72-year-old White man of British origin with metastatic castrate-resistant prostate cancer with bulky lymphadenopathy and a serum prostate-specific antigen of 295 μg/L. He received treatment with docetaxel chemotherapy plus prednisolone, but received just 3 cycles before treatment was stopped due to toxicity and lack of response (prostate-specific antigen was 276 μg/L 4 weeks after the last dose and there was a confirmed stable appearance on computed tomography scan). Unexpectedly, at follow-up 4 months later, the patient was clinically better; his prostate-specific antigen had dramatically improved to 4.1 μg/L and a re-staging computed tomography scan revealed complete resolution of his bulky lymphadenopathy. At the time, he was receiving a luteinising hormone-releasing hormone analogue but no other disease-modulating treatment. He remains well and asymptomatic, with his most recent serum prostate-specific antigen measuring 0.14 μg/L, 18 months after last receiving chemotherapy.. We report a case of complete and durable regression of metastatic castrate-resistant prostate cancer following palliative chemotherapy which, to the best of our knowledge, has not previously been reported in the literature.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Docetaxel; Goserelin; Humans; Lymphatic Metastasis; Male; Nitriles; Prostate; Prostatic Neoplasms; Taxoids; Tosyl Compounds; Treatment Failure; Treatment Outcome

To investigate acceptability of and preferences for physical activity participation in men receiving androgen-deprivation therapy (ADT) for prostate cancer, to identify influencing clinical and demographic factors, and to determine the percentage meeting national exercise guidelines.. Cross-sectional, descriptive.. Ambulatory care clinic of a large medical center.. 135 men receiving ADT.. A structured interview with a systematic procedure was used to elicit preferences for physical activity.. Exercise preferences and acceptability; evidence-based exercise intervention.. Participants expressed high levels of acceptability of and willingness to participate in aerobic (64% and 79%) and muscle-strengthening (79% and 81%) programs. Preferences were expressed for muscle-strengthening activities performed at home, either alone or in the company of a family member. Flexible, spontaneous, and self-paced programs were preferred. Significant associations were identified for distance, age, obesity, duration of ADT, and meeting American College of Sports Medicine (ACSM) and American Heart Association (AHA) guidelines. Nineteen percent of the study population met the guidelines for weekly physical activity.. High levels of expressed acceptance of and willingness to participate in physical activity programs as well as the small number of participants meeting ACSM and AHA guidelines suggest feasibility of and support the need for the development of exercise programs in this population.. Incorporating patient preferences and evidence-based practice is integral to providing high-quality patient-centered care and is the foundation for appropriate intervention programs. Insight from this study will facilitate the design of programs that better reflect actual preferences of prostate cancer survivors.. ADT-induced changes in body composition are believed to contribute to a reduction in insulin sensitivity and dyslipidemia that contribute to increased cardiovascular risk profile. Exercise has the potential to mitigate the harmful effects of ADT.

Topics: Adenocarcinoma; Aged; Androgens; Antineoplastic Agents, Hormonal; Bone Density; Cross-Sectional Studies; Exercise; Feasibility Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Insulin Resistance; Male; Middle Aged; Muscle Strength; Neoplasms, Hormone-Dependent; Patient Acceptance of Health Care; Patient Preference; Practice Guidelines as Topic; Prostatic Neoplasms; Resistance Training; Socioeconomic Factors

We report a case of squamous differentiated prostate carcinoma that developed after combination endocrine therapy for adenocarcinoma of the prostate. The patient was a 68-year-old man who visited our hospital with microscopic hematuria. His serum prostate-specific antigen (PSA) level was 7. 06 ng/ml. Transperineal needle biopsy was performed and histological examinations indicated moderately differentiated adenocarcinoma with a Gleason score of 4 + 4 = 8. Computed tomography showed swelling of left external iliac lymph node. The clinical stage was T3aN1M0. Six weeks after combination endocrine therapy using goserelin acetate and bicalutamide, the patient underwent radical prostatectomy and bilateral pelvic lymphadenectomy. Histopathological examination of the surgical specimen demonstrated squamous cell carcinoma of the prostate with very small areas of adenocarcinoma. The treatment measure was changed from endocrine therapy to combination chemotherapy consisting of docetaxel, cisplatin, and 5- FU. Eighteen month has passed after the surgery without any evidence of distant metastasis.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Docetaxel; Fluorouracil; Goserelin; Humans; Lymph Node Excision; Male; Nitriles; Prostatectomy; Prostatic Neoplasms; Taxoids; Tosyl Compounds

Osteosarcoma of the prostate is a rare finding. These tumours usually occur years after radiotherapy for prostate cancer. We report the case of a 74-year-old man with prostate cancer who had been treated with radiotherapy and androgen deprivation therapy. The man presented with urinary retention and his prostate was transurethrally resected. The histopathological investigation showed formations of a poorly differentiated osteosarcoma in the prostate. Because of serious comorbidities we decided to withhold chemotherapy considering its potential side effects. The man died a few months after the diagnosis of osteosarcoma in the prostate with the disease in a metastatic stage. In conclusion, osteosarcoma of the prostate is a rarely reported consequence of radiotherapy in patients with prostate cancer and is characterised by poor life expectancy.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Combined Modality Therapy; Disease Progression; Fatal Outcome; Goserelin; Humans; Male; Neoadjuvant Therapy; Neoplasm Staging; Neoplasms, Radiation-Induced; Neoplasms, Second Primary; Nitriles; Prostatic Neoplasms; Tosyl Compounds; Transurethral Resection of Prostate

Topics: Adenocarcinoma; Adenoma; Aged; Antineoplastic Agents, Hormonal; Gonadotrophs; Goserelin; Humans; Male; Pituitary Neoplasms; Prostatic Neoplasms

The first case was in a 73-year-old man with macrohematuria. The second case was in a 59-year-old man with pollakiuria. Their serum prostate specific antigen levels were slightly elevated and urinary cytology was negative. Histological examination by prostatic needle biopsy and biopsy from bladder neck showed prostatic ductal adenocarcinoma. Clinical stage on computed tomography and magnetic resonance imaging was T4N0M0 in both cases. After 10-month maximal androgen blockade(MAB) and arterial chemotherapy using reservoir system, radiation therapy was performed. After that, low dose FP-chemotherapy(5-fluorouracil 600 mg/day, cisplatinum 10 mg/day) was performed for 28 days in the first case. At present, there are no signs of recurrence or metastasis in either case.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Fluorouracil; Goserelin; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Prostatic Neoplasms; Treatment Outcome

Over the last decade, epidemiological, experimental and clinical studies have implicated oxidative stress in the development and progression of prostate cancer. In the present study, we evaluated the oxidative status and antioxidant defense in patients with prostate cancer (PCa) taking into consideration: treatment, Gleason score and bone metastasis. For this, we measured concentrations of plasmatic thiobarbituric acid reactive substances (TBARS), serum protein carbonylation, whole blood catalase (CAT) and superoxide dismutase (SOD) activities, as well as the plasma and erythrocyte thiol levels and serum vitamin C and E concentration. This study was performed on 55 patients with PCa and 55 healthy men. TBARS levels and serum protein carbonylation were higher in PCa patients than in controls and altered levels of antioxidants were found in these patients. CAT activity was decreased and SOD activity was higher in PCa patients when compared with controls. Non-protein thiol levels were increased, however, serum vitamin C and vitamin E content were reduced in PCa patients when compared with controls. In addition, different parameters analyzed in PCa patients based on metastasis, treatment and Gleason score showed changes in oxidative stress biomarkers and antioxidant defenses. These findings may indicate an imbalance in the oxidant/antioxidant status, supporting the idea that oxidative stress plays a role in PCa, moreover, the oxidative profile appear to be modified by bone metastasis, treatment and Gleason score.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Ascorbic Acid; Bone Neoplasms; Catalase; Cyproterone Acetate; Erythrocytes; Goserelin; Humans; Lipid Peroxidation; Male; Middle Aged; Neoplasm Grading; Oxidative Stress; Prostatic Neoplasms; Protein Carbonylation; Sulfhydryl Compounds; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin E

In order to assess the efficacy and toxicity of oral estramustine phosphate (EMP) administration, low-dose EMP monotherapy (study 1) and very low-dose EMP therapy with luteinizing hormone-releasing hormone (LH-RH) agonist (study 2) were conducted in previously untreated prostate cancer and long-term outcomes were compared between the 2 study groups.. Studies 1 and 2 were independently performed beginning in June 1999 and November 2001, respectively. Study 1 was composed of 87 patients including 85 assessable patients. All 108 patients recruited for study 2 were assessable. Low-dose EMP monotherapy (2 capsules/day or 280 mg/day) was used in study 1 and very low-dose EMP (1 capsule/day or 140 mg/day) combined with LH-RH agonist was adopted in study 2.. Overall prostate specific antigen (PSA) -response rates in studies 1 and 2 were 92.3% and 94.2%, respectively, and overall toxicity rates were 54.1% and 38.9%, respectively. EMP discontinuation due to side effects was encountered more often in study 1 (45.9%) than in study 2 (27.8%). Among the adverse side effects gastrointestinal toxicity was most prevalent in both studies. One patient died of acute pulmonary embolism in study 1, but no one died in study 2. There were 6 cancer deaths in the gastrointestinal tract in study 1 but only 2 cancer deaths in study 2.. Our data indicate that the overall PSA response rate was comparable between both studies. However, rates in overall toxicity and drug discontinuation were higher in study 1 than in study 2. We consider that study 2 is more promising for the treatment of previously untreated advanced prostate cancer, although the rate of adverse side effects is still high as compared with other hormonal therapies. In order to overcome the high toxicity rate, especially the gastrointestinal toxicity, we recently elaborated a method employing tailor-made medicine using SNPs of 1A1 gene in cytochrome P-450 for decreasing the rate of gastrointestinal toxicity. Using this method of patient selection, study 3 has been successfully launched on September 2005 with high drug compliance. Better clinical results are being accumulated.

Topics: Adenocarcinoma; Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Biomarkers, Tumor; Cause of Death; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Estramustine; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Injections, Intravenous; Kaplan-Meier Estimate; Leuprolide; Male; Middle Aged; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Cardiovascular Diseases; Chemotherapy, Adjuvant; Cyproterone Acetate; Disease-Free Survival; Dose Fractionation, Radiation; Drug Administration Schedule; Fractures, Bone; Goserelin; Humans; Lymphatic Metastasis; Male; Neoplasm Invasiveness; Neoplasm Staging; Patient Selection; Prostatic Neoplasms; Risk Assessment; Time Factors; Treatment Outcome

We report the case of an 80-year-old man who presented with relapsing prostate cancer and cerebral metastases which showed evidence of radiological and clinical response to androgen suppression alone without additional whole brain radiotherapy.

Topics: Adenocarcinoma; Aged, 80 and over; Antineoplastic Agents, Hormonal; Brain Neoplasms; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease Progression; Goserelin; Humans; Male; Neoplasm Grading; Neoplasm Recurrence, Local; Prostatic Neoplasms; Tomography, X-Ray Computed; Transurethral Resection of Prostate

Topics: Adenocarcinoma; Adult; Amenorrhea; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Drug Administration Schedule; Estradiol; Female; Fertility Agents, Female; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Goserelin; Humans; Infertility, Female; Luteinizing Hormone; Lymph Node Excision; Mastectomy; Menstruation; Ovary; Ovulation; Primary Ovarian Insufficiency; Progesterone; Prospective Studies; Time Factors; Treatment Outcome

Topics: Adenocarcinoma; Adult; Amenorrhea; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Estradiol; Female; Fertility Agents, Female; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Goserelin; Humans; Infertility, Female; Luteinizing Hormone; Lymph Node Excision; Mastectomy; Menstruation; Ovary; Ovulation; Primary Ovarian Insufficiency

We describe a patient with node positive prostate cancer treated with radiation, androgen deprivation, and immunotherapy with long-term overall survival and PSA control. ELISPOT immunoassay studies demonstrated PSA specific T-cells prior to starting vaccine therapy suggesting that this positive response may be related to an improved antitumor immune response of the patient, increased immunogenicity of the tumor, or decreased activation of immune escape pathways. Further evaluation of therapeutic cancer vaccines in combination with radiation and hormonal therapy in the definitive management of prostate cancer is warranted.

Topics: Adenocarcinoma; Anilides; Antineoplastic Agents, Hormonal; B7-1 Antigen; Cancer Vaccines; Goserelin; Humans; Lymphatic Metastasis; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Engineering; Radiography, Abdominal; Radiotherapy; T-Lymphocytes; Tosyl Compounds; Ultrasound, High-Intensity Focused, Transrectal; Vaccines, Synthetic

An 87-year-old man visited our hospital, complaining of abdominal distention and inability to urinate. Computed tomography (CT) and magnetic resonance imaging revealed a giant prostate tumor. The patient underwent percutaneous tumor biopsies. The histologic diagnosis was moderately differentiated adenocarcinoma of prostate. The clinical stage according to the TNM classification system was T4N0M0, stage IV. Combined androgen blockade therapy was performed. Four months later, CT showed that the tumor had decreased markedly in size, and the serum prostate specific antigen level was within normal range. Hormone refractory prostate cancer was not found 1 year after the start of treatment.

Topics: Adenocarcinoma; Adrenergic alpha-Antagonists; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Chlormadinone Acetate; Drug Administration Schedule; Drug Therapy, Combination; Goserelin; Humans; Magnetic Resonance Imaging; Male; Naphthalenes; Nitriles; Piperazines; Prostate-Specific Antigen; Prostatic Neoplasms; Tosyl Compounds

To elucidate the crucial predictors for prostate-specific antigen (PSA) trends and determine the usage of anti-androgen treatment during delayed-combined androgen blockade (CAB) leading to a PSA level below 0.2 ng/mL.. From January 2001 to December 2004, 105 prostate cancer patients were enrolled. Medical castration and anti-androgen treatment were used sequentially and termed delayed-CAB. The first goal was to maintain an undetectable PSA level. The nadir PSA was determined after medical castration only. Anti-androgen was given if a PSA level of more than 0.2 ng/mL was observed and the subsequent PSA response was assessed. All cases were divided into two groups based on whether the PSA was lower (n = 59) or higher (n = 46) than 0.2 ng/mL. An analysis of the difference between the two groups was calculated.. The median of the initial PSA level in the lower group was lower than in the higher group with a 95% cut-off level of 40 ng/mL. The median PSA half-life in the lower group was also reduced with a 95% cut-off of 3.6 months. In a multivariate analysis, the pretreatment PSA level and the PSA half-life exhibited a significant correlation between the two groups. Anti-androgen treatment was given to 26 cases in the higher group. The PSA increased in one case, decreased to less than 0.2 ng/mL in 17 cases and remained over 0.2 ng/mL in eight cases.. Both the PSA half-life and the pretreatment PSA level were useful markers for predicting the PSA trends to determine the optimal use of anti-androgen treatment during delayed-CAB.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Drug Therapy, Combination; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Nitriles; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Tosyl Compounds; Treatment Outcome

A 74-year-old male was treated with endocrine therapy for localized prostate cancer. After 25 months he complained of a swollen neck, and was diagnosed with prostate cancer with lymph node metastasis of neuroendocrine differentiation. Neuroendocrine differentiation without elevation of conventional tumor markers is rare during the initial recurrent course of localized prostate cancer.

Topics: Adenocarcinoma; Aged; Anilides; Antineoplastic Agents, Hormonal; Cell Differentiation; Goserelin; Humans; Lymphatic Metastasis; Male; Neoplasm Recurrence, Local; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Tosyl Compounds

Peritoneal carcinomatosis is a rare finding in metastatic prostate cancer. In the literature peritoneal carcinomatosis is usually reported in its final stages with multiple metastases. A single peritoneal carcinomatosis with no further metastases is a very rare finding.. We report the case of a 75-year-old patient with initial ischuria. A prostate cancer could be confirmed and the further diagnostics showed no metastasis. In a transperitoneal approach for laparoscopic pelvic lymphadenectomy a peritoneal carcinomatosis from prostate cancer was proven. A complete antiandrogen therapy was started and PSA decreased for more than 14 months to a stable level of < 1 microg/L.. An isolated peritoneal carcinomatosis from prostate cancer is a very rare finding. The complete antiandrogen therapy is effective.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Follow-Up Studies; Goserelin; Humans; Lymph Node Excision; Male; Nitriles; Peritoneal Neoplasms; Peritoneum; Prostate-Specific Antigen; Prostatic Neoplasms; Time Factors; Tosyl Compounds; Transurethral Resection of Prostate; Treatment Outcome

Prostate cancer (PCa) is the most commonly diagnosed cancer in American men with a subset inevitably presenting with metastatic disease to the bone. A well-recognized limitation in evaluating new treatments for metastatic PCa is the inability to use imaging to objectively assess response therapy. In this study, we evaluated the feasibility of clinically translating the functional diffusion map (fDM) imaging biomarker for quantifying the spatiotemporal effects of bone tumor response in a patient treated for metastatic PCa with bone metastases. A patient beginning therapy was scanned using MRI before treatment and again at 2 and 8 weeks post-treatment initiation to quantify changes in tumor diffusion values. Three metastatic lesions were identified for fDM analysis, all of which all demonstrated an early increase in diffusion values at 2 weeks, which increased further at 8 weeks post-treatment initiation. This finding correlated with a decrease in the patient's prostate-specific antigen (PSA) levels suggestive of patient response. CT, bone scans, and anatomic MRI images obtained posttreatment were found to be uninformative for the assessment of treatment effectiveness. This study presents the feasibility of fDM-measurements in osseous lesions over time and shows that changes in fDM values were consistent with therapeutic response. Thus, the fDM imaging biomarker may provide a quantifiable therapeutic endpoint to assess response in patients with metastatic bone cancer.

Topics: Adenocarcinoma; Aged; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Body Water; Bone Neoplasms; Cell Membrane Permeability; Diffusion Magnetic Resonance Imaging; Feasibility Studies; Goserelin; Humans; Male; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Tomography, X-Ray Computed; Tosyl Compounds; Treatment Outcome; Whole Body Imaging

In Radiation Therapy Oncology Group (RTOG) trial 92-02, after men received neoadjuvant hormone cytoreduction and radiotherapy for locally advanced prostate carcinoma, they were randomized to receive either 2 years of long-term androgen-deprivation (LTAD) or no further treatment (short-term androgen-deprivation [STAD]). The specific objective of the current study was to determine whether LTAD was a cost-effective treatment for patients with locally advanced prostate carcinoma.. The cost-effectiveness of LTAD was tested using a Markov model that was designed using proprietary software. The analysis took a payor's perspective. Unit costs were obtained by estimation using a global Medicare fee schedule. Costs and outcomes were discounted by 3%. Distributions were sampled at random from the treatment utilities, transition probabilities, and costs using a second-order Monte Carlo simulation technique.. The expected mean cost was 32,564 dollars for LTAD compared with 33,039 dollars for STAD after accounting for the additional cost of salvage treatment for men who were treated with STAD. The mean number of quality-adjusted life years (QALYs) for men who received LTAD was 4.13 QALYs compared with a mean of 3.68 QALYs for men who received STAD. The cost-effectiveness acceptability curve analysis showed a 91% probability that LTAD was cost-effective compared with STAD. Although overall survival was similar in the LTAD and STAD groups, the patients who received LTAD experienced gains in QALYs and had lower costs, because LTAD prevented biochemical failure and the necessitating salvage hormone therapy.. The current analysis showed that LTAD was cost-effective for the entire population studied in RTOG trial 92-02.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Cost-Benefit Analysis; Flutamide; Goserelin; Humans; Male; Markov Chains; Monte Carlo Method; Neoadjuvant Therapy; Prostatic Neoplasms; Quality-Adjusted Life Years; Radiotherapy, Conformal; Randomized Controlled Trials as Topic

We describe a patient with advanced prostate cancer who failed to achieve testosterone suppression with depot leuprolide after developing sterile abscesses at the injection sites. When the patient was switched to depot goserelin, he did not have any evidence of inflammation at the injection sites, but testosterone suppression again failed. This case suggests variable mechanisms for failure of gonadotropin-releasing hormone agonist therapy and highlights the necessity of prospective testosterone monitoring in patients who have developed sterile abscesses, even if switched to another gonadotropin-releasing hormone agonist.

Topics: Abscess; Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Bone Neoplasms; Delayed-Action Preparations; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Nitriles; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Tosyl Compounds; Treatment Failure

To prospectively assess the efficacy and tolerability of bicalutamide monotherapy on biochemical failure of localized prostate cancer following total androgen deprivation (TAD) and 3D-conformal radiotherapy (3D-CRT).. Between January 1998 and January 2002, we prospectively evaluated 20 eligible patients with biochemical failure. All patients were initially treated with neoadjuvant TAD of 12 weeks before 3D-CRT (73.6 Gy at isocenter) and same regimen of TAD after completion of radiotherapy for 24 weeks in high-risk patients. We prescribed 150 mg/day bicalutamide monotherapy for 24 weeks in patients with biochemical failure according to American Society for Therapeutic Radiology and Oncology 1997 consensus definition. Primary end points were biochemical control (BC) and metastasis-free survival (MFS).. Median follow-up was 28 months after biochemical failure date. At last visit, the median PSA level of all patients was 2.80 ng/dl while 1.28 ng/dl for nonmetastatic and 30.7 ng/dl for metastatic patients. BC was successfully obtained in five of them with only bicalutamide. Ten patients developed distant metastasis among 15 patients receiving salvage TAD. MFS was 55% at three years for all 20 patients. Temporary gynecomasty was observed in 11 patients as the only serious toxicity.. Bicalutamide monotherapy seems to be a tolerable regimen for patients with biochemical failure following 3D-CRT, and TAD and may be effective in patients with low PSA levels at biochemical failure.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Disease Progression; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Nitriles; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, Adjuvant; Radiotherapy, Conformal; Tosyl Compounds; Triptorelin Pamoate

To assess the factors effecting PSA bounce and to identify any possible relationship with biochemical control after 3-D conformal radiotherapy (3D-CRT) and total androgen deprivation (TAD) for prostate cancer by evaluating four previously described PSA bounce definitions.. Between January 1998 and January 2001, 83 consecutive patients with clinically localized prostate cancer were treated by 3D-CRT with neoadjuvant 3 months and/or 6 months adjuvant TAD. All patients had a pretreatment PSA level, at least eight post-external beam radiotherapy (EBRT) PSA and testosterone levels and minimum two years of follow-up. Total radiotherapy dose was 73.6 Gy at ICRU reference point. Four previous definitions of PSA bounce were used: Critz definition (>or=0.1 ng/mL), Cavanagh definition (>or=0.2 ng/mL), Hanlon definition (>or=0.4 ng/mL) and Rosser definition (>or=0.5 ng/mL) according to original methodology performed to report PSA bounce. Biochemical failure was defined in accordance with the ASTRO consensus guidelines.. The median follow-up time was 40 months. PSA bounce was recorded as follows: Critz definition, 33 patients (40%); Cavanagh definition, 21 patients (25%); Hanlon definition, 11 patients (13%); and Rosser definition, 7 patients (8%). In multivariate analysis, pre-EBRT PSA level and the duration of TAD for Critz definition; age, pre-EBRT PSA and the duration of TAD for Cavanagh definition; age and duration of TAD for Hanlon definition; age and pre-biopsy PSA for Rosser definition were significant independent prognostic factors determining PSA bounce. A significant increase of mean testosterone level in bouncers was detected at the 6th-9th and 18th-21st months. PSA bounce did not predict for PSA failure in multivariate analysis.. We observed no correlation between biochemical failure and PSA bounce. The longer duration of TAD and older age were found to be inversely proportional with PSA bouncing in this cohort. Notably, recovery of testosterone might cause PSA bouncing.

Topics: Adenocarcinoma; Aged; Androgens; Antineoplastic Agents, Hormonal; Disease Progression; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, Adjuvant; Radiotherapy, Conformal; Regression Analysis; Retrospective Studies; Testosterone; Time Factors; Treatment Outcome; Triptorelin Pamoate

We report a case of a seminal vesicle cyst supposed to be associated with prostate cancer in a 79-year-old Japanese man presenting with urinary retention. A fist-sized soft mass was palpated at the anterior wall of the rectum and serum prostate-specific antigen (PSA) was elevated to 59.8 ng/ml. Transrectal ultrasonography, computed tomography and magnetic resonance imaging revealed a retrovesical cystic mass measuring 7 cm in diameter and the absence of bilateral seminal vesicles. On vasography the lumen of the cystic lesion was visualized immediately, but the radiopaque fluid did not flow into the urethra. Transperineal prostate biopsy revealed moderately differentiated adenocarcinoma and puncture of the cyst revealed bloody fluid including sperm with a low PSA level. These findings strongly suggested that the mass was a seminal vesicle cyst caused by ejaculatory duct obstruction associated with prostate cancer. He has received endocrine therapy with goserelin acetate and bicalutamide for 6 months with no enlargement of the cystic lesion.

Topics: Adenocarcinoma; Aged; Anilides; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cysts; Diagnostic Imaging; Ejaculatory Ducts; Genital Diseases, Male; Goserelin; Humans; Male; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Seminal Vesicles; Tosyl Compounds

To better understand bone metabolism and predict bone loss in treatment using gonadotropin-releasing hormone agonist for patients with prostate cancer.. The changes in bone mineral density and blood levels of bone metabolism markers and the level of pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen, a specific marker of bone resorption, and carboxy-terminal pro-peptide of human type I procollagen, a specific marker of bone formation, were examined in 27 consecutive patients with prostate cancer without bone metastasis.. After 2 years of gonadotropin-releasing hormone treatment, the bone mineral density was significantly lower (median 0.937 g/cm2) than before treatment. Pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen began to increase significantly 6 months after the start of treatment (3.0 to 8.3 ng/mL, median 4.6, at baseline versus 3.4 to 8.2 ng/mL, median 5.2, after 6 months). Carboxy-terminal pro-peptide of human type I procollagen began to show a significant rise 1 year after the start of treatment (from 72.8 to 221.5 ng/mL, median 102.0, at baseline to 82.7 to 293.4 ng/mL, median 132.0, at 1 year).. Functional coupling between bone resorption and formation was noted, and a decrease in bone mass, even in men, owing to androgen deficiency, was biochemically demonstrated. Fluctuations in these two bone metabolism markers preceded the decrease of bone mineral density. Therefore, these markers might be a predictor of bone loss.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers; Bone and Bones; Bone Density; Bone Remodeling; Bone Resorption; Collagen Type I; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Osteoporosis; Peptide Fragments; Peptides; Procollagen; Prostatic Neoplasms; Testosterone

Our patient was a 61-year-old man with hormone-refractory prostate cancer and a rapidly rising serum prostate-specific antigen level. During the course of therapy for prostate cancer, abnormal blood counts and subsequent bone marrow biopsy led to a diagnosis of acute lymphoblastic leukemia. He was treated with a chemotherapeutic regimen in standard use for lymphoblastic leukemia, which resulted in an unusual response of his prostate cancer, with declining serum prostate-specific antigen levels that had reached undetectable levels at the time of the patient's death from acute sepsis and leukemic relapse. Autopsy showed minimal evidence of prostate cancer, localized to the prostate.

Topics: Adenocarcinoma; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Drug Resistance, Neoplasm; Fatal Outcome; Goserelin; Humans; Immunocompromised Host; Male; Methotrexate; Middle Aged; Neoplasm Proteins; Neoplasms, Second Primary; Neutropenia; Nitriles; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prostate-Specific Antigen; Prostatic Neoplasms; Recurrence; Sepsis; Tosyl Compounds; Vincristine

A 66-year-old male patient with advanced prostate cancer presented with bony metastases, including pathologic fractures and hepatosplenomegaly. The patient responded to luteinizing hormone-releasing hormone agonists for more than 1 year. A clear progression while taking luteinizing hormone-releasing hormone agonists manifested as a progressive rise in prostate-specific antigen, alkaline phosphatase, hepatosplenomegaly, and myelophthisic pancytopenia. We administered capecitabine for 5 months with a complete clinical response. At last follow-up, the patient's liver function tests and prostate-specific antigen level have normalized. Liver size by computed tomography and blood counts both improved. To our knowledge, no previous case reports of capecitabine in the treatment of prostate cancer have been published.

Topics: Adenocarcinoma; Aged; Alkaline Phosphatase; Antimetabolites, Antineoplastic; Antineoplastic Agents, Hormonal; Capecitabine; Deoxycytidine; Fluorouracil; Goserelin; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Failure; Treatment Outcome

Late chronic side effects of the rectum constitute one of the principal limiting factors for curative radiation therapy in patients with prostate cancer. The purpose of the study was to determine the impact of immediate androgen deprivation (IAD) prior to conformal radiotherapy on rectal volume exposed to high doses, as compared with a deferred treatment strategy (DAD). Twenty-five patients (13 in the IAD group and 12 in the DAD group) with bulky tumours of the prostate, T3pN1-2M0 from the prospective EORTC trial 30846 were analysed. Three-dimensional conformal radiation treatment plans (3DCRT) using a 4-field box technique were generated based on the digitized computed tomographic or magnetic resonance findings acquired during the first 9 months after inclusion in the EORTC trial. Dose-volume histograms (DVHs) were calculated for the prostate and rectum. In the DAD group, there was no obvious alteration in the mean size of the prostate or other evaluated structures. In the IAD patients, a statistically significant reduction of approximately 40% of the gross tumour volume (GTV) was reached after a 6 months' course of hormonal treatment (p < 0.001). High-dose rectal volume was correlated with the volume changes of the GTV (p < 0.001). Mean rectal volume receiving 95% or more of the target dose was significantly reduced by 20%. Our study confirms the effect of downsizing of locally advanced prostate tumours following AD treatment and demonstrates the interdependence of the high-dose rectal volume with the volume changes of the GTV. However, the mean beneficial sparing of rectal volume was outweighed in some patients by considerable inter-patient variations.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Combined Modality Therapy; Cyproterone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Prostatic Neoplasms; Radiotherapy Dosage; Radiotherapy, Conformal; Rectum

The purpose of this investigation was to explore the potential benefit of hormone therapy in addition to external beam radiotherapy for patients with early-stage (T1-2), intermediate-(prostate-specific antigen [PSA] > 10 or Gleason score >or= 7) or high-risk (PSA > 10 and Gleason score >or= 7) prostate cancer. The charts of 412 patients with early-stage intermediate- and high-risk prostate cancer treated with external beam radiotherapy with or without a 4-month total androgen blockade were reviewed. The groups were balanced with respect to age, pretreatment PSA, and stage, but differed with respect to Gleason score and radiation dose. Biochemical failure rates, as defined by the ASTRO consensus panel, were compared between those receiving and those not receiving hormones. With a median follow-up of 2.0 years, the biochemical failure rate was 12.1 versus 23.1% (p = 0.02) in favor of those receiving hormones. This difference was seen for the subgroups followed for more than 6 months (12.5 vs. 25.0%), more than 9 months (14.5 vs. 26.3%), and more than 12 months (17.3 vs. 27.0%). Thus, biochemical failure decreased with the administration of hormone therapy in this group of patients with early stage, intermediate- or high-risk prostate cancer. This finding requires validation by ongoing randomized trials.

Topics: Adenocarcinoma; Aged; Anilides; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Flutamide; Goserelin; Humans; Male; Neoadjuvant Therapy; Nitriles; Prostatic Neoplasms; Survival Analysis; Tosyl Compounds

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Diagnosis, Differential; Goserelin; Humans; Male; Middle Aged; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatectomy; Prostatic Neoplasms; Testis; Testosterone

The objective of this work was to determine the effect of androgen deprivation therapy (ADT) on rates of bone mineral density (BMD) loss in men with prostate cancer. It was a prospective study comparing men receiving ADT to age matched controls for 2 y. Subjects received a history, physical exam, bone mineral density measurement, and laboratory evaluation every 6 months. Thirty-nine subjects receiving continuous ADT for prostate cancer (subjects) were compared to 39 age-matched controls not receiving ADT (controls). Twenty-three subjects and 30 controls completed the study through 24 months. Men in the ADT group demonstrated greater rates of bone mineral density loss than men in the control group at every site except the lumbar spine. Twenty-four month per cent of bone mineral density loss is presented as mean+/-standard error (s.e.). At the distal forearm, the ADT group value was -9.4%+/-1.0% and -4.4%+/-0.3% for controls (P<0.0005). The ADT group femoral neck values were -1.9%+/-0.7% and 0.6%+/-0.5% in the control group (P=0.0016). The ADT group total hip value was -1.5%+/-1.0% and 0.8%+/-0.5% in the control group (P=0.0018). The ADT group trochanter value was -2.0%+/-1.3% and -0.1%+/-0.5% in the control group (P=0.0019). The ADT group lumbar spine value was -0.2%+/-0.8 % and 1.1%+/-0.6% in the control group (P=0.079). Our data demonstrate greater rates of bone mineral density loss in men receiving androgen deprivation therapy for prostate cancer.

Topics: Absorptiometry, Photon; Adenocarcinoma; Aged; Amino Acids; Androgen Antagonists; Androgens; Anilides; Antineoplastic Agents, Hormonal; Biomarkers; Bone Density; Bone Remodeling; Calcium; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Neoplasms, Hormone-Dependent; Nitriles; Orchiectomy; Osteoporosis; Prospective Studies; Prostatic Neoplasms; Testosterone; Tosyl Compounds

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Fatigue; Gonadotropin-Releasing Hormone; Goserelin; Hot Flashes; Humans; Male; Multicenter Studies as Topic; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms; Quality of Life; Radiotherapy, Conformal; Randomized Controlled Trials as Topic; Sexual Dysfunction, Physiological; Survival Rate; Testosterone; Treatment Outcome

We assessed the degree of prostate downsizing using androgen deprivation, and determined its relation to clinical and pathological variables.. From June 1994 to January 2000, 107 patients with prostate cancer received androgen deprivation before interstitial brachytherapy at our hospital. All charts were reviewed for clinical, pathological and treatment related variables. Prostate volume was measured using transrectal ultrasound. All variables were analyzed with regard to the degree of prostate downsizing.. Mean percent volume reduction of the prostate was 33% after a 3.7-month average duration of androgen deprivation. Larger prostate volume before androgen deprivation and longer deprivation duration statistically correlated with mean percent volume reduction. Simple linear and multiple regression analyses revealed that these 2 variables remained significant predictors of percent volume reduction. Subgroup analysis indicated that a significant difference was seen in patients who received androgen deprivation with luteinizing hormone releasing hormone agonists alone versus those who received treatment with total androgen blockade (luteinizing hormone releasing hormone agonists plus antiandrogens 30% versus 35%, p = 0.04), and when prostate volume before androgen deprivation was less than 50 cc versus larger volumes (30% versus 35%, p = 0.01). Of patients with an initial prostate volume of greater than 50 cc 82% achieved a volume of less than 50 cc after androgen deprivation therapy.. Androgen deprivation therapy before brachytherapy is a method of downsizing the prostate to overcome anatomical limitations, including larger gland volume and pubic arch interference.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Brachytherapy; Combined Modality Therapy; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostate; Prostatic Neoplasms; Regression Analysis; Ultrasonography

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Disease Progression; Drug Resistance, Neoplasm; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms

Cachexia is rarely observed in patients with advanced prostate cancer treated with combined androgen blockade. Androgens play an important role in the regulation of body mass composition and influence the secretion of leptin, the appetite regulating hormone. The aim of the study was to assess the influence of a combined treatment with nonsteroidal antiandrogen and LH-RH analogue on the hormonal regulation of appetite and changes in body mass in patients with advanced prostate cancer (Whitmore-Jewett stage D1 or D2). Eighteen patients with prostate cancer and 17 healthy subjects matched for age and body mass index were included. In all patients serum concentrations of leptin, neuropeptide Y (NPY), insulin, testosterone and estradiol were measured before and after four and twelve weeks of androgen blockade. Pretreatment serum leptin levels were similar in patients with prostate cancer and in the controls. In a multiple regression analysis only body mass index and testosterone significantly contributed to the variation of plasma leptin. During the treatment body mass and plasma leptin significantly increased while NPY decreased. The change of plasma NPY was significant only after 4 weeks of therapy. This study shows that the afferent regulation of leptin secretion is unchanged in advanced prostate cancer. Androgen ablation significantly increases body mass and influences secretion of appetite regulating hormones. Testosterone appears to play a significant role in the regulation of leptin secretion.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Appetite; Body Constitution; Body Mass Index; Body Weight; Estradiol; Flutamide; Goserelin; Humans; Insulin; Leptin; Male; Middle Aged; Neuropeptide Y; Prostatic Neoplasms; Regression Analysis; Testosterone

In the clinical study of prostate cancer, the effect of androgen ablation on glucose metabolism in cancer tissue has not been elucidated. The purpose of this study was to investigate the change in glucose utilization due to endocrine therapy for prostate adenocarcinoma. Ten patients with histologically proven prostate cancer were prospectively investigated with (18)F-fluorodeoxyglucose and positron emission tomography (FDG PET) prior to and after the initiation of endocrine therapy. FDG uptake was calculated to measure glucose utilization in cancer tissue. The change in FDG accumulation was compared with changes in serum prostate specific antigen (PSA) level and prostate size. FDG accumulation in the prostate decreased in all patients 1-5 months after the initiation of hormone therapy. The serum PSA level and prostate size measured on computerized tomography (CT) also decreased in these periods. A decrease in FDG accumulation was also demonstrated in metastatic sites. In this study, there appeared to be a decrease in FDG uptake in prostate cancer after endocrine therapy not only in primary prostate cancer lesions but also at metastatic sites, suggesting that the glucose utilization by tumours was suppressed by androgen ablation.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Fluorodeoxyglucose F18; Glucose; Goserelin; Humans; Male; Middle Aged; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Tomography, Emission-Computed

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Goserelin; Humans; Male; Pituitary Apoplexy; Prostatic Neoplasms

This report confirms experimental data on direct inhibitory effects of LH-RH agonists in growth control of human prostate cancer cells. The patient had hormone-refractory prostatic carcinoma after hormonal therapy, including orchiectomy, and responded successfully to a 6-month treatment with goserelin acetate (3.6 mg depot s.c.). The treatment has led to a reduction of tumor mass and metastases as well as an improvement in the patient's paraclinical indicators and general status. The remission lasted 14 months. The treatment still continues.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Drug Resistance, Neoplasm; Gonadotropin-Releasing Hormone; Goserelin; Humans; Lymphatic Metastasis; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms

Permanent androgen ablation has been the mainstay of treatment for advanced prostate cancer. However, the favorable outcome seen in recent pilot studies of intermittent androgen ablation raises the possibility of overtreatment.. This study included 35 Japanese men with advanced prostate cancer. Initial androgen ablation continued for 2 months after PSA levels decreased to <4.0 ng/ml, then was withdrawn. Androgen ablation was reinstituted 2 months after PSA reached levels >10 ng/ml, when indicated clinically or on patient request. Cycling continued until androgen independence was reached.. Mean follow-up was 21.0 months, representing an average of 2.5 cycles. Nine patients developed androgen independence at an average of 16.0 months following androgen ablation; three of these have died. Six of the nine patients with early biochemical progression had elevated alkaline phosphatase levels at entry; five of these exhibited a flare in alkaline phosphatase activity after initiation of androgen ablation. Mean bone mineral density (BMD) in the lumbar spines of 17 patients was 81.5 mg/cm3 at 23 months following therapy. The BMD of 10 of these patients was normal for their age. Four patients suffered bone fractures, none pathological.. Intermittent androgen ablation may be an option for patients with advanced prostate cancer and may be especially beneficial for those with initially low BMD levels. Patients with elevated alkaline phosphatase levels at entry or a flare in its activity may not be ideal candidates. Whether prolonging time to androgen independence will provide benefit remains to be investigated in a randomized, prospective study.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Alkaline Phosphatase; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Density; Disease Progression; Drug Administration Schedule; Flutamide; Follow-Up Studies; Fractures, Bone; Goserelin; Humans; Leuprolide; Lumbar Vertebrae; Male; Middle Aged; Pilot Projects; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction; Survival Rate; Testosterone; Treatment Outcome

Recent studies have demonstrated that angiogenesis is a potent prognostic indicator for patients with prostate cancer (PCa) and have pointed out that the evaluation of vascular endothelial growth factor (VEGF) is useful in assessing the angiogenic phenotype in PCa. The aim of the study was to investigate immunohistochemically the expression of VEGF and its correlation with the pattern of capillary architecture in prostate cancer and high-grade prostatic intraepithelial neoplasia (PIN), in untreated and androgen-ablated patients.. Forty-five patients who underwent radical prostatectomy (RP) for localized prostate carcinoma were recruited for this study. The study population included two groups: 35 patients who did not receive chemo-, hormone, or radiation therapy before surgery, and 10 patients who were under complete androgen blockade (CAB) for 3 months at time of surgery. VEGF was examined by immunohistochemistry, and its tissue expression was compared with the pattern of capillary architecture evaluated by immunostaining the endothelial antigen CD34. The relationship of VEGF expression to chromogranin A-positive (e.g., neuroendocrine) cells was investigated.. In normal tissue, the intensity of the VEGF immunoreactivity in the cytoplasm of secretory cells ranged from negative to low. Very few basal cells stained for VEGF. All prostate cancer specimens stained positively, the intensity of the immunoreaction ranging from low to strong and being correlated with the Gleason score. Strongly positive VEGF immunoreactivity was detected in vascular endothelial cells and in stromal cells surrounding blood vessels. Two discrete immunostaining patterns were observed in high-grade PIN. VEGF expression of low-to-moderate intensity was defined as pattern A. The other, characterized by a strong cytoplasmic immunoreaction similar to that of poorly differentiated tumors, was defined as pattern B. The capillary architecture in high-grade PIN with pattern A was similar to the orderly vascular network seen in normal prostates, whereas in the pattern B it had the characteristics of microvessels usually seen in PCa. The degree of vascularization in the stroma adjacent to intensely VEGF-stained cells (neuroendocrine phenotype) was higher than that noted in association with secretory cells. CAB before surgery downregulated the expression of VEGF and decreased the degree of vascularization, except in the cell areas with neuroendocrine (NE) features.. Our immunohistochemical results indicate that significant levels of VEGF are present in prostate cancer and in a population of PIN lesions, expression being highest in association with NE cells. VEGF expression is downregulated by hormonal manipulation, except in the population of NE cells.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Combined Chemotherapy Protocols; Capillaries; Endothelial Growth Factors; Goserelin; Humans; Immunohistochemistry; Lymphokines; Male; Middle Aged; Neovascularization, Pathologic; Nitriles; Prostatectomy; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Tosyl Compounds; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Patients with prostate cancer are treated with neoadjuvant, adjuvant and intermittent androgen deprivation therapy. Prostate specific antigen (PSA) is altered during androgen deprivation therapy, and as a result the prognostic significance and accuracy of PSA values measured before serum testosterone has normalized are questionable because the patient is still effectively on androgen deprivation therapy. We determine the time it takes for serum testosterone to return to normal after withdrawal of androgen deprivation therapy.. Serial serum testosterone was prospectively measured at 3-month intervals in 68 men after withdrawal of androgen deprivation therapy. The number of months to return to normal serum testosterone 270 ng./dl. or greater, was calculated for each patient. Patients were stratified according to duration of androgen deprivation, age and type of luteinizing hormone releasing hormone agonist used.. Median patient age was 71 years (range 46 to 88). Median time to normalization of testosterone was 7 months (range 1 to 58). At 3, 6 and 12 months 28%, 48% and 74% of men had normal serum testosterone, respectively. Serum testosterone took significantly longer to return to normal in patients on androgen deprivation therapy for 24 months or greater compared to those on therapy for less than 24 months (log-rank p = 0.0034). There was no statistical significance based on age or type of luteinizing hormone releasing hormone agonist used.. Androgen deprivation has an effect on serum testosterone that extends beyond the cessation of treatment. Serum testosterone should be measured in all men until normalization. These results should be applied to the interpretation of PSA levels after withdrawal of androgen deprivation therapy. In addition, these data have implications regarding dose scheduling and definition of biochemical (PSA) failure after primary therapy.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Testosterone; Time Factors

We report the results of surgery in 520 patients with clinically localized carcinoma of the prostate (CaP) who received preoperative neoadjuvant hormonal therapy (NHT) for 3 to 11(+) months.. The results in the NHT patients were compared with those in 1,413 men having surgery without NHT at our institution during the same time period. In the group without pretreatment, the median and mean follow-up was 36 and 21 months, respectively. In the patients receiving NHT, the median follow-up was 33 months and the mean 41 months.. The overall disease-free survival (DFS) rate (serum prostate specific antigen [PSA] concentration < or = 0.2 ng/mL) was 75% at 5 years and 50% at 10 years. There was no statistically significant difference in overall DFS rate between men who had NHT and those who did not. No DFS advantage could be demonstrated for those patients with a presenting PSA >20 ng/mL who received NHT compared with patients with the same PSA concentration who did not receive NHT. Despite our previous experience indicating improved survival with NHT in men with a presenting PSA of > 10 ng/mL, we could find no advantage to NHT in enhancing DFS. At a median survival of 35 months (mean 41 months) in 201 men with an initial PSA > or = 10 ng/mL, 70% had an undetectable PSA concentration at 5 years compared with 72% at the same time point in men presenting with PSA <10 ng/mL. In the group expected to have the best surgical result; i.e. those men whose preoperative PSA was < or = 7 ng/mL, there was no DFS difference in men given NHT compared with those having no hormonal manipulation. Patients presenting with stage T(1) disease had a significantly better DFS than those with either T(2) or T(3) CaP. However, within each stage, the addition of NHT to surgery did not result in a higher DFS rate. The 5- and 10-year DFS rates for stage T(1) were 80% and 64%, for T2 disease 78% and 50%, and for T3 disease 67% and 50%. There was a statistically significant difference (P < or = 0.003) in survival between stage T(1) and stage T(2) disease, but no significant difference in DFS was noted in patients presenting with stage T(2) compared with T3 cancer (P = 0.431). Gleason score was not a significant predictor of durable DFS, and the addition of NHT did not improve the DFS within groups of patients with similar Gleason scores. Men with only one or two positive biopsy cores did significantly better than those with more than three positive cores (P = 0.06). There was a significant difference in DFS between men who had organ-confined disease and those with disease outside the gland (P = 0.0003). However, NHT did not improve DFS. The presence of positive surgical margins was a negative prognostic factor (P = 0. 001). Men who received NHT had a statistically lower positive margin rate (P = 0.001), but NHT did not increase the likelihood of a durable DFS (P = 0.175). The duration of NHT did not affect the DFS (P = 0.100 for <3 v >3 months).. There appears to be no subset of men undergoing radical prostatectomy in whom the routine administration of NHT is beneficial despite the statistically significant improvement in the pathologic findings.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents, Hormonal; Biopsy; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Disease-Free Survival; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Time Factors

In hemodialysis patients, few cases of prostate cancer have been reported until recently. We present a case of prostate cancer with multiple lung metastases in a chronic hemodialysis patient. A 65-year-old Japanese man who had maintained hemodialysis for 5 years was referred to our hospital with multiple metastatic lung tumors. Serum prostate tumor markers were highly elevated although his plasma testosterone level was within the normal range. A transrectal needle prostate biopsy confirmed a histologic diagnosis of moderately differentiated adenocarcinoma. Androgen blockade therapy was very effective as evidenced by a quick decrease of serum tumor markers. The follow-up computed tomography scan of the chest performed 3 months later showed a complete disappearance of the coin lesions. The early detection of prostate cancer in hemodialysis patients is difficult because of a lack of urologic symptoms, which indicate the importance of periodic screening by serum tumor markers. Combined androgen blockade is effective even in hemodialysis patients. However, close follow up is necessary because long-term results and prognoses are still unknown.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Drug Therapy, Combination; Flutamide; Goserelin; Humans; Lung Neoplasms; Male; Prostatic Neoplasms; Radiography, Thoracic; Renal Dialysis; Tomography, X-Ray Computed

To determine the change in volume of the prostate as a result of neoadjuvant androgen deprivation prior to prostate implant and in the early postimplant period following transperineal ultrasound guided palladium-103 brachytherapy for early-stage prostate cancer.. Sixty-nine men received 3 to 6 months of androgen deprivation therapy followed by treatment planning ultrasound followed 4 to 8 weeks later by palladium-103 implant of the prostate. All patients had clinical and radiographic stage T1c-T2b adenocarcinoma of the prostate. A second ultrasound study was carried out 11 to 13 days following the implant to determine the change in volume of the prostate as a result of the implant. The prehormonal and preimplant volumes were compared to the postimplant volume to determine the effect of hormones and brachytherapy on prostate volume.. The median decrease in prostate volume as a result of androgen deprivation was 33% among the 54 patients with prostate volume determinations prior to hormonal therapy. The reduction in volume was greatest in the quartile of men with the largest initial gland volume (59%) and least in the quartile of men with smallest glands (10%). The median reduction in prostate volume between the treatment planning ultrasound and the follow-up study after implant was 3%, but 23 (33%) patients had an increase in prostate volume, including 16 (23%) who had an increase in volume >20%; 11 of these patients (16%) had an increase in volume >30%. The time course of development and resolution of this edema is not known. The severity of the edema was not related to initial or preimplant prostate volume or duration of hormonal therapy.. Prostate edema may significantly affect the dose delivered to the prostate following transperineal ultrasound guided brachytherapy. The effect on the actual delivered dose will be greater when shorter lived isotopes are used. It remains to be observed whether this edema will affect outcome.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Brachytherapy; Combined Modality Therapy; Dose-Response Relationship, Radiation; Goserelin; Humans; Iodine Radioisotopes; Leuprolide; Male; Palladium; Prostatic Neoplasms; Radiopharmaceuticals; Ultrasonography, Interventional

A 72-year-old man presented with pollakiuria and dysuria. His prostate was the size of an apple and hard on digital rectal examination and the serum prostate specific antigen (PSA) level was 73 ng/ml (RIA). Ultrasonography revealed bilateral hydronephrosis and the serum creatinine level was 13.2 mg/dl. CT scanning of the abdomen demonstrated swelling of paraaortic lymph nodes. Transrectal needle biopsy of the prostate gave a diagnosis of moderately differentiated adenocarcinoma. Accordingly, the final diagnosis was prostate cancer (cT3N4M1, stage D2). Immediately after bilateral percutaneous nephrostomy, treatment with an LH-RH agonist (goserelin) and flutamide was commenced. Serum creatinine was 6.6 mg/dl at the start of antiandrogen therapy and decreased to 1.8 mg/dl after 27 days. A 125 mg flutamide capsule was administered at 7 a.m., and blood samples were collected 4 hours later on days 1, 2, 3, 5, 6, 8, 12, 14, 17, 18 and 27. The OH-flutamide concentration was measured. There was no significant correlation between serum creatinine and the OH-flutamide concentration. After implantation of goserelin (3.6 mg depot), blood samples were obtained at 11 a.m. on days 8, 12, 14, 15 and 25. The serum goserelin level was measured. The serum goserelin level increased to a peak on day 14, as described previously, but the peak value of 9.63 ng/ml was higher than that reported before (mean +/- SD 2.848 +/- 0.199).

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Flutamide; Goserelin; Humans; Hydronephrosis; Male; Prostatic Neoplasms; Ureteral Obstruction

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Goserelin; Humans; Male; Prostatic Neoplasms

The p53 tumor suppressor gene (also known as TP53) is one of the most frequently mutated genes in human cancer. Several studies have shown that p53 mutations are infrequent in prostate cancer and are associated with advanced disease.. We assessed the prognostic value of identifying abnormal p53 protein expression in the tumors of patients with locally advanced prostate cancer who were treated with either external-beam radiation therapy alone or total androgen blockade before and during the radiation therapy.. The study population consisted of a subset of patients entered in Radiation Therapy Oncology Group protocol 8610 ("a phase III trial of Zoladex and flutamide used as cytoreductive agents in locally advanced carcinoma of the prostate treated with definitive radiotherapy"). Immunohistochemical detection of abnormal p53 protein in pretreatment specimens (i.e., needle biopsies or transurethral resections) was achieved by use of the monoclonal anti-p53 antibody DO7; specimens in which 20% or more of the tumor cell nuclei showed positive immunoreactivity were considered to have abnormal p53 protein expression. Associations between p53 protein expression status and the time to local progression, the incidence of distant metastases, progression-free survival, and overall survival were evaluated in univariate (logrank test) and multivariate (Cox proportional hazards model) analyses. Reported P values are two-sided.. One hundred twenty-nine (27%) of the 471 patients entered in the trial had sufficient tumor material for analysis. Abnormal p53 protein expression was detected in the tumors of 23 (18%) of these 129 patients. Statistically significant associations were found between the presence of abnormal p53 protein expression and increased incidence of distant metastases (P = .04), decreased progression-free survival (P = .03), and decreased overall survival (P = .02); no association was found between abnormal p53 protein expression and the time to local progression (P = .58). These results were independent of the Gleason score and clinical stage. A significant treatment interaction was detected with respect to the development of distant metastases: Among patients receiving both radiation therapy and hormone therapy, those with tumors exhibiting abnormal p53 protein expression experienced a reduced time to the development of distant metastases (P = .001); for patients treated with radiation therapy alone, the time to distant metastases was unrelated to p53 protein expression status (P = .91).. Determination of p53 protein expression status yield significant, independent prognostic information concerning the development of distant metastases, progression-free survival, and overall survival for patients with locally advanced prostate cancer who are treated primarily with radiation therapy.. The interaction of radiation therapy plus hormone therapy and abnormal p53 protein expression may provide a clinical link to experimental evidence that radiation therapy and/or hormone therapy act, at least in part, by the induction of apoptosis (a cell death program) and suggests that this mechanism may be blocked in patients whose tumors have p53 mutations.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Disease Progression; Disease-Free Survival; Flutamide; Gene Expression Regulation, Neoplastic; Genes, p53; Goserelin; Humans; Male; Middle Aged; Mutation; Prognosis; Prostatic Neoplasms; Radiotherapy, Adjuvant; Survival Analysis; Tumor Suppressor Protein p53

It is unclear if continuing with androgen deprivation in hormone-refractory prostate cancer is of any benefit. We report here 3 cases where continuation of androgen deprivation was essential in maintaining the response to chemotherapy.. In the 3 patients there was an initial response to chemotherapy before relapse, as assessed by prostate-specific antigen levels. However, restarting the previously ineffective hormone therapy resulted in continued response to chemotherapy.. In some patients continued androgen deprivation is essential to the response to chemotherapy. Presumably, in hormone-relapsed disease a significant proportion of the tumour can still be responsive to androgen deprivation.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Diethylstilbestrol; Disease Progression; Epirubicin; Fluorouracil; Goserelin; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Bone Neoplasms; Goserelin; Humans; Male; Middle Aged; Orchiectomy; Palliative Care; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Treatment Failure

In the light of a case of left orbital metastasis, constituting the presenting sign of prostatic cancer in a 60-year-old man, the authors emphasize the rarity of this site, despite the high frequency of bone metastases in this disease. They discuss the diagnostic methods and stress the need for urgent treatment to save ocular function.

Topics: Adenocarcinoma; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Diethylstilbestrol; Emergencies; Goserelin; Humans; Injections, Intravenous; Male; Methylprednisolone Hemisuccinate; Middle Aged; Orbital Neoplasms; Prostatic Neoplasms; Vision, Ocular

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Goserelin; Humans; Male; Middle Aged; Palliative Care; Penile Neoplasms; Prostatic Neoplasms

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Goserelin; Humans; Male; Prostatic Neoplasms; Survival Analysis

The aim of this study was to investigate the effect of goserelin-acetat (Zoladex) on testosterone suppression, to compare achieved suppression with clinical effects in patients with prostate cancer with bone metastases and consequent painful syndrome, to study the behavior of adiol during treatment and to assess life quality with emphases on the physical and psychological domain in relation to clinical and biological treatment effects. Fifteen patients were treated by Zoladex in one dose every 28 days, and followed-up for 12 months. All patients had several metastatic localizations in the bones, initial high prostate specific antigen (PSA), and high acid (AP) and alkaline phosphatase (ALP). PSA, testosterone, adiol (delta-5-androstenediol), luteinizing hormone (LH), foliculostimulating hormone (FSH), ALP and AP were also measured before every cycle. For evaluation of the life quality Rotterdam Symptom Checklist was used. Clinical progression was not registered during follow-up, with drop of PSA, ALP and AP. Testosterone and adiol displayed mainly inverse trends during treatment. The complete testosterone suppression was never achieved. It seems that Zoladex has quite different influence on LH and FSH, as levels of those hormones have shown opposite trend. Some of the observed hormonal effects could be attributed to stimulation of the monoamine system. Suppression of LH level provoked by administration of LHRH agonists increases level of dopamine in hypothalamus which inhibits releasing of its hormones. By inhibition of corticotropic releasing factor and ACTH, and by its influence on adrenal gland, we could explain drop of adiol levels in the first months of administration of LHRH agonists. Testosterone increase and adiol drop in the first months, and adiol increase following testosterone level drop in the fourth to eight month, may be explained by negative feed back mechanism between different androgens which could be stimulated or provoked by LHRH therapy. The question of effects which are results of LHRH agonists modulation of the monoamine system and consequent activation of other central mechanisms of hormonal regulation is still open. Patients' quality of life under therapy was improved for about 30% in psychological and functional domains. There were no significant changes on physical subscale, during treatment. It seems that the obtained positive psychological treatment effect is not only a consequence of pain decrease, but it could be the result o

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Alkaline Phosphatase; Androstenediol; Antineoplastic Agents, Hormonal; Bone Neoplasms; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Quality of Life; Testosterone

Relapsing polychondritis is a chronic rheumatologic disorder of unknown etiology. Cutaneous manifestations occur in nearly half of the patients and often precede cartilaginous involvement. We present the case of a man with a history of prostatic adenocarcinoma who underwent monthly injections of goserelin (Zoladex), an LH-RH analogue. Five months after the beginning of the treatment, he presented cutaneous manifestations, which then recurred monthly, after each goserelin injection. After goserelin interruption and replacement with another treatment (cyproterone acetate), the patient was asymptomatic for 2 months. A cutaneous relapse then occurred followed by a typical cartilaginous involvement. In our observation, goserelin seems to have triggered the cutaneous manifestations of relapsing polychondritis. An hormonal precipitating factor in relapsing polychondritis has already been suggested by reports of patients whose disease worsened under chorionic gonadotropin treatment or during pregnancy.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Cartilage Diseases; Cyproterone; Drug Eruptions; Erythema; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Polychondritis, Relapsing; Prostatic Neoplasms; Purpura; Recurrence

Preirradiation hormonal cytoreduction of prostate cancer has been proven to reduce exposure of normal structures by decreasing the size of the target volume. Dose-volume histogram (DVH) analysis, however, does not always appear to demonstrate a strong positive benefit with the use of neoadjuvant hormone therapy. This study analyzes various other factors influencing dose to normal organs, which may determine the success or failure of neoadjuvant hormonal therapy in achieving its goals.. Patients with bulky clinical Stage C adenocarcinoma of the prostate were given 3 months of hormone treatment consisting of oral Flutamide and monthly Zoladex injections prior to irradiation. Computerized tomography (CT) scans of the pelvis were obtained both prior to and following hormonal treatment. Treatment plans were generated by three-dimensional (3D) conformal treatment planning. The change in the volume of the prostate was assessed along with the percentage of prescribed dose delivered to the rectum and bladder. Various factors such as prostate size, bladder/rectum size, and organ shape were studied. Both dose-volume histograms (DVH) and dose-surface area histograms (DSH) were used for analysis.. Six of seven patients had reduction in the size of their prostates. The mean volumes of the prostate before and after hormonal manipulation were 129.1 +/- 32.9 standard deviation (SD) cm3 and 73.0 +/- 29.5 SD cm3, respectively (p = 0.0059). The volume of rectum receiving 80% of the prescribed dose was reduced in five of seven patients from a mean of 83.2 to 59.9 cm3 (p = 0.045). The volume of bladder receiving 80% of the prescribed dose was also reduced in five out of seven patients from a mean of 74.5 to 40.2 cm3 (p = 0.098). Correlation between the size of the prostate and volume of rectum and bladder treated was not always consistent: greater reduction in prostate size did not necessarily result in large decreases in dose to bladder or rectum. The total size of the bladder and rectum were found to be important factors in normal tissue radiation exposure; the benefits of hormone therapy may be lost if the bladder and rectum are allowed to decrease in size. Also, the bladder may be prone to sagging into the pelvis of some patients following hormone therapy, resulting in a less optimal therapeutic ratio.. Reduction in prostate size by neoadjuvant hormonal manipulation does decrease the amount of normal tissue irradiated in most patients. However, the correlation between the reduction in prostate size and amount of rectum or bladder treated is not linear if other variables are not controlled. Factors such as the shape of the organs, as well as the distensible nature of the bladder and rectum, play major roles in dose to normal tissues. These facts may mask the benefits of cytoreduction and could be obstacles in realizing consistent benefits from preirradiation hormonal treatment in the clinical setting if they are ignored.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Flutamide; Goserelin; Humans; Male; Prostate; Prostatic Neoplasms; Radiotherapy Dosage; Rectum; Retrospective Studies; Urinary Bladder

The patient was a 38-year-old woman who was diagnosed as having right breast cancer (T1aN1bM0, stage II) at the age of 36 when she underwent right mastectomy. Postoperative adjuvant therapy was performed using UFT and tamoxifen. After 2 years and 4 months, pulmonary metastasis was diagnosed from elevated tumor markers and chest X-P. After the relapse, treatment with goserelin acetate (Zoladex) and CPA was started. After 2 months of this treatment, the tumor in the lung had shrunk in size, and after 5 months partial remission (PR) was evaluated from improvements in chest X-P and normalization of tumor markers, This PR condition continues at present. A case report is presented of a patient with premenopausal recurrent breast cancer in whom good results were obtained by concomitant administration of Zoladex and CPA.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Female; Goserelin; Humans; Lung Neoplasms; Mastectomy; Premenopause; Remission Induction

Eighty-two patients with stage T3 carcinoma of the prostate were treated for 3 months prior to radical retropubic prostatectomy with a luteinizing-hormone-releasing hormone analogue and an antiandrogen. Based on digital rectal examination (DRE), reduction of prostate and tumor size was noted in all cases. Ultrasound demonstrated a decrease in prostatic volume between 0 and 62.5% (median 32%). Prostate-specific antigen levels (PSA, Hybritech) decreased substantially (mean PSA of 29.5 ng/ml before to a mean PSA of 1.3 ng/ml after hormonal treatment). Pathologically, only 15 patients (18.3%) had organ-confined disease (stage pT2), 44 (53.7%) had stage pT3 tumors and 22 (26.8%) had positive lymph nodes. In 1 surgical specimen (1.2%), no residual tumor was identified. In 5 patients with nodal metastasis and 13 patients with seminal vesicle invasion, PSA levels after pretreatment were below 0.5 ng/ml. Compared to the preoperative needle biopsy, a decrease in the histological grade was found in only 7 tumors, while an increase was noted in 26. DRE, ultrasound and PSA suggest a downstaging of stage T3 prostate cancer after 3 months of maximum androgen deprivation. This cannot be confirmed pathologically. Prospective studies with this treatment regimen should concentrate on a possible benefit concerning local and distant cancer control and survival.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Prostatectomy; Prostatic Neoplasms

Topics: Acid Phosphatase; Adenocarcinoma; Goserelin; Humans; Male; Parotid Neoplasms; Prostate; Prostate-Specific Antigen; Remission Induction

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Combined Modality Therapy; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Lymphatic Metastasis; Male; Middle Aged; Palliative Care; Prostatectomy; Prostatic Neoplasms; Quality of Life

Topics: Adenocarcinoma; Aged; Goserelin; Humans; Male; Middle Aged; Osteoporosis; Prostatic Neoplasms

Since postcastration progression of tumors to an androgen-independent state appears to be linked to the cessation of androgen-induced differentiation of tumorigenic stem cells, the authors hypothesized that the replacement of androgens at the end of a period of apoptotic regression might result in the regeneration of differentiated tumor cells with further apoptotic potential.. To determine the effect of intermittent exposure of androgens on the androgen-dependent Shionogi carcinoma, the tumor was transplanted into a succession of male mice, each of which was castrated when the estimated tumor weight became about 3 g. After the tumor had regressed to 30% of the original weight, it was transplanted into the next noncastrated male. This cycle of transplantation and castration-induced apoptosis was repeated successfully four times before growth became androgen-independent during the fifth cycle. In four of Stage C and three of Stage D patients with prostate cancer, androgen withdrawal was initiated with cyproterone acetate (100 mg/d) and diethylstilbestrol (0.1 mg/d) and then maintained with cyproterone acetate in combination with the luteinizing hormone-releasing hormone agonist, goserelin acetate (3.6 mg/month). After 6 or more months of suppression of serum prostate-specific antigen (PSA) into the normal range, treatment was interrupted for 2 to 11 months. After recovery of testicular function, androgen-withdrawal therapy was resumed when serum PSA increased to a level of about 20 micrograms/l. This cycle was repeated sequentially to a total of two to four times over treatment periods of 21 to 47 months with no loss of androgen dependence.. These results demonstrate that intermittent androgen suppression can be used to induce multiple apoptotic regressions of a tumor; they also suggest that the cyclic effects of such treatment on prostate cancer can be followed by the sequential measurement of serum PSA levels.

Topics: Adenocarcinoma; Aged; Animals; Apoptosis; Cyproterone Acetate; Diethylstilbestrol; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Mammary Neoplasms, Experimental; Mice; Middle Aged; Neoplasm Staging; Neoplasm Transplantation; Neoplasms, Hormone-Dependent; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

A 65-year-old man with advanced prostate cancer was treated with a luteinizing hormone-releasing hormone (LH-RH) analogue. Four days after the initial injection of 3.6 mg of goserelin acetate, severe dyspnea developed due to worsening pleuritis carcinomatosa, which was considered as a flare-up. Chest drainage was required to save his life. Therefore, we emphasize the importance of treatment to prevent tumor flare during LH-RH analogue therapy.

Topics: Adenocarcinoma; Aged; Drainage; Goserelin; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Pleural Effusion, Malignant; Prostatic Neoplasms

Topics: Adenocarcinoma; Aged; Drug Resistance; Flutamide; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

Ten patients with non-extirpable adenocarcinoma of the pancreas received monthly subcutaneous implantations of the LHRH analogue goserelin. Subjective improvement (diminished abdominal pain and/or weight gain) occurred within 3 months in seven patients and persisted until about 2 months before death. The treatment was well tolerated by the patients. This preliminary study seems to warrant further investigation of goserelin in the management of pancreatic cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Buserelin; Drug Implants; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Pancreatic Neoplasms; Prospective Studies

79 patients with locally advanced and/or metastatic prostate cancer were treated by means of a biodegradeable depot formulation of the luteinizing hormone releasing hormone analogue Goserelin (Zoladex). All patients received 3.6 mg depot Goserelin (Zoladex 3.6 mg implantate) subcutaneously into the anterior abdominal wall at 4 weekly intervals. The average time of observation was 24.2 months. The best objective response rate was found in 62%. Serum testosterone levels initially increased after the first depot injection and then decreased ultimately to castrate range (less than 0.6 ng/ml) between day 15 and day 27 (median 21) in the majority of patients. Castrate testosterone levels were still found 48 months after the start of treatment with depot Goserelin. 6 months after institution of treatment in 66.7% of cases evident signs of histological regression were found in the primary tumour tissue. Adenocarcinoma presented with a highly significantly better response pattern than anaplastic carcinoma. In animal experiments a single dose of 1 mg depot Goserelin was administered to adult male rats and the effect on serum testosterone levels and target organs (testes and ventral prostate) were investigated. Mean testosterone levels (mean = 0.31 ng/ml) decreased to castrate range (less than 0.3 ng/ml). 4 weeks after depot injection weight of the testes and prostate weight were significantly reduced. However 8 weeks after administration of 1 mg depot Goserelin there was no significant between the control group and the treated group. We conclude that the depot formulation of Goserelin (Zoladex) is effective, simple, practicable and safe in the treatment of advanced prostatic cancer. Current clinical studies are confirming the importance of reversible medical castration by LHRH agonists before radical prostatectomy.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Animals; Buserelin; Carcinoma; Drug Implants; Goserelin; Humans; Male; Middle Aged; Organ Size; Prospective Studies; Prostate; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Testis; Testosterone

A luteinizing hormone-releasing hormone (LH-RH) analogue was administered for 3 to 32 months to 15 prostatic cancer patients in stage B-D (B:3, C:8, D:4). Intratesticular, intratubular and prostatic androgen levels were measured by radioimmunoassay before and after LH-RH analogue therapy. The measurement of serum prostatic acid phosphatase (PAP) and prostatic specific antigen (PA) levels was also conducted. Thereafter, we assessed the effect of the LH-RH analogue on androgen levels and the relation of prostatic tissue 5 alpha-dihydrotestosterone (DHT) level to the clinical response. The results were as follows: 1) Johnsen's mean germinal epithelium count was significantly decreased from 7.7 +/- 2.1 (mean +/- S.D.) to 4.3 +/- 2.3, and the wall thickness of seminiferous tubules was increased from 5.93 +/- 1.31 to 11.9 +/- 3.64 microns. 2) Plasma testosterone (T), intratesticular and intratubular androgen levels were significantly decreased (plasma T: from 4.40 +/- 1.84 to 0.61 +/- 0.32 ng/ml, intratesticular T: from 335.3 +/- 170.3 to 4.6 +/- 3.8 ng/g.t.w., DHT: from 25.3 +/- 11.7 to 3.7 +/- 2.7 ng/g.t.w., intratubular T: from 50.8 +/- 36.6 to 0.10 +/- 0.99 ng/g.t.w. and DHT: 7.54 +/- 3.20 to 0.63 +/- 0.90 ng/g.t.w.). 3) Crude nuclear DHT levels in prostatic tissue fell from 15.3 +/- 9.3 (N = 8) to 0.37 +/- 0.54 pg/mg protein (N = 3) and the level was non-detectable in 5 of 8 cases. 4) Complete remission was achieved in 1 patient, partial response in 5, objective stable in 8, and objective progression in 1 patient, according to Shimazaki's criteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgens; Antineoplastic Agents; Buserelin; Dihydrotestosterone; Drug Evaluation; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Remission Induction; Testosterone

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Buserelin; Carcinoma in Situ; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Goserelin; Humans; Lymphatic Metastasis; Mastectomy, Segmental; Menopause; Middle Aged; Neoplasm Staging; Prognosis; Tamoxifen

Serum concentrations of gonadotropins, testosterone and dehydrotestosterone were determined in patients receiving conventional endocrine therapy for advanced metastatic adenocarcinoma of prostate. The effect over 4 h of a single dose of a long acting analogue of LHRH was determined in these patients and compared to the response in patients receiving the analogues as first choice of treatment. Oestrogen therapy was found to suppress basal and stimulated gonadotropins and testicular androgens. Cyproterone therapy only partially reduced basal hormone concentrations and the response to the LHRH analogue was delayed. Orchidectomy resulted in elevated gonadotropins and an exaggerated response to the analogue. As patients who relapse while failing conventional therapy, may subsequently be treated by further endocrine manipulation, precise determination of their endocrine status should predict any expected benefit. Patients previously treated with stilboestrol are unlikely to respond to orchidectomy or LHRH analogue.

Topics: Adenocarcinoma; Buserelin; Castration; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Prostatic Neoplasms; Testosterone

Topics: Adenocarcinoma; Aged; Drug Resistance; Drug Therapy, Combination; Gonadotropin-Releasing Hormone; Goserelin; Humans; Ketoconazole; Male; Prostatic Neoplasms