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PubMed1990

Combination therapy with flutamide and medical (LHRH agonist) or surgical castration in advanced prostate cancer: 7-year clinical experience.

Three hundred and sixty-three patients with clinical stage D2 prostate cancer who had not received previous endocrine therapy or chemotherapy were treated with the combination therapy using the pure antiandrogen Flutamide and the LHRH agonist [D-Trp6,des-Gly-NH2(10)]LHRH ethylamide (or orchiectomy) for an average of 771 days (24-2607 days). Only 31 of the 308 evaluable patients (10.1%) did not show an objective positive response at the start of the combination therapy compared with an average of 18% in five recent studies using monotherapy. The median survival achieved using monotherapy is approximately 24 months while, in the present study, it is increased to 41.2 months, thus giving an additional 17 months of survival with the combination therapy. It should be mentioned that at the time of relapse, combination therapy is continued and, in addition, further blockade of adrenal androgen secretion is achieved with aminoglutethimide and hydrocortisone. While our studies showing the advantages of combination therapy with pure antiandrogen in advanced prostate cancer have been confirmed by independent large-scale randomized studies, our preliminary data clearly suggest the interest of downstaging early stage prostate cancer by temporary combination therapy prior to radical prostatectomy.

Adenocarcinoma↗
PubMed2004

Severe, generalized nummular eczema secondary to interferon alfa-2b plus ribavirin combination therapy in a patient with chronic hepatitis C virus infection.

BACKGROUND: With increasing rates of hepatitis C virus infection and diagnosis, more patients are being treated with interferon alfa-2b plus ribavirin therapy. Cutaneous side effects to combination therapy are common and may limit treatment. There are few previous case reports of generalized eczematous dermatoses occurring after combination therapy for hepatitis C virus, none in a North American patient, and none of this severity or recalcitrance. OBSERVATIONS: A man with chronic hepatitis C virus infection and no history of atopy developed severe, recalcitrant nummular eczema secondary to interferon alfa-2b plus ribavirin combination therapy. The cutaneous side effect was more severe than in previously reported cases and did not remit on discontinuation of therapy. CONCLUSIONS: Greater awareness of the range of dermatologic responses to interferon alfa-2b plus ribavirin therapy may lead to improved surveillance for and treatment of these side effects. Investigating the underlying pathologic mechanisms may ultimately allow for a greater understanding of the immunomodulatory effects of this therapy in the setting of chronic hepatitis C virus infection.

Antiviral Agents↗
PubMed2002

The rationale for combination therapy.

The use of combination lipid-altering therapy for dyslipidemia is becoming increasingly important for effective management of patients with coronary heart disease (CHD). In accordance with the Adult Treatment Panel III guidelines, the primary target of therapy is lowering low-density lipoprotein (LDL) cholesterol. Studies have demonstrated the benefit of LDL cholesterol reduction in decreasing CHD event rates and all-cause mortality. However, low high-density lipoprotein (HDL) cholesterol remains a significant predictor of CHD events. In addition, lipid-lowering therapy targeting aberrant lipoprotein subclass and triglyceride levels afford additional benefit for patients with mixed dyslipidemias. Aggressive lipid-altering therapy often requires the use of combination therapy involving statins in conjunction with niacin, fibric-acid derivatives, or bile acid resins or intestinal inhibitors of active cholesterol transport. This article reviews the rationale for the use of combination therapy in the treatment of dyslipidemia, highlighting management strategies.

Anticholesteremic Agents↗
PubMed2001

Combination therapy in angina: a review of combined haemodynamic treatment and the role for combined haemodynamic and cardiac metabolic agents.

The 1997 European Society of Cardiology guidelines emphasised medical therapy as the mainstay of treatment of stable angina. Until recently, the antianginal drugs available to control symptoms (nitrates, beta-blockers and calcium antagonists) have all been haemodynamic agents that eliminate or reduce angina attacks principally by decreasing myocardial oxygen demand. They may also improve myocardial perfusion. The haemodynamic agents are often used in combination. However, there is conflicting evidence for the efficacy of combination treatment. Two recently published large clinical studies, the Total Ischaemic Burden European Trial (TIBET) study and the International Multicenter Angina Exercise (IMAGE) study, suggest that combined haemodynamic treatment is no more effective than optimal monotherapy. The results from IMAGE suggest that most of the additional effect observed with combined therapy was attributable to recruitment by the second drug of patients who had not responded to monotherapy, and that most patients continued to have a disturbing frequency of anginal attacks after receiving combined therapy. Metabolic agents are a new class of drugs that directly modify the use of energy substrates in the heart, lessening ischaemic injury and improving cardiac performance during ischaemia. Due to their non-haemodynamic mode of action, metabolic agents such as trimetazidine or L-carnitine may provide independent benefit in ischaemia when used as monotherapy or additional benefit when used in combination with a conventional agent. Clinical trials have shown that combined haemodynamic and metabolic treatment is more effective than combined haemodynamic therapy and is well tolerated. It is suggested that combination haemodynamic and metabolic therapy is a logical new approach to patients whose angina is inadequately controlled despite optimal haemodynamic therapy.

Adrenergic beta-Antagonists↗
PubMed2006

[A case of exacerbation of ulcerative colitis induced by combination therapy with PEG-interferon alpha-2b and ribavirin for chronic hepatitis C].

A 55-year-old man with chronic hepatitis C had diarrhea with bloody stool in July, 2003 and ulcerative colitis was suspected. However, he quickly improved. He was treated with percutaneous radiofrequency ablation therapy for adenomatous hyperplasia in S5 of the liver in December, 2004. After the ablation therapy, he was treated with combination therapy of PEG-interferon alpha-2b and ribavirin for chronic hepatitis C. Because exacerbation of ulcerative colitis appeared 10 weeks after beginning of the treatment for hepatitis C, the combination therapy of PEG-interferon and ribavirin was discontinued. He was treated with mesalazine and steroid therapy for ulcerative colitis, and improved. We report the first case in Japan of the exacerbation of ulcerative colitis induced by the combination therapy of PEG-interferon and ribavirin for chronic hepatitis C.

Antiviral Agents↗
PubMed2002

Rationale for combination therapy of intraurethral prostaglandin E(1) and sildenafil in the salvage of erectile dysfunction patients desiring noninvasive therapy.

Corpus cavernosum smooth muscle relaxation and hence penile erection are regulated in part by increases in smooth muscle synthesis of the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). The object of this study was to determine 30-month follow-up results in motivated patients desiring noninvasive medical therapy using sildenafil citrate (Viagra) in combination with intraurethral prostaglandin E(1) (PGE(1)) (Medicated Urethral System for Erection [MUSE]). Twenty-eight patients (mean +/- s.d. age, 59 +/-7.3 y; 17 who had undergone radical prostatectomy and 11 who had a diagnosis of organic erectile dysfunction) were included in this study. Detailed history taking and physical examinations were performed and vascular risk factors noted. In these patients, treatment with either 100 mg of sildenafil citrate and/or 1000 microg of MUSE had failed. None of these patients desired intracavernosal injection. Duplex Doppler ultrasonography after redosing was carried out on all patients. Dynamic infusion corpus cavernosography/cavernosometry was obtained in 17 of 28 patients, and combination therapy was initiated using 100 mg of sildenafil citrate orally 60 min before intercourse and 500 microg of MUSE intraurethrally immediately before intercourse. Independently, either 100 mg of sildenafil citrate or 1000 microg of MUSE was not efficacious in inducing an erection sufficient for vaginal penetration in any of the 28 patients. After initiating a combination therapy, at 30 months, all 28 patients were reporting erections sufficient for vaginal penetration, with 3.6 intercourse episodes per month. None of the patients crossed over to intracavernosal therapy or penile prosthesis. During therapy, eight of 28 patients reduced the dose of sildenafil citrate to 50 mg. Combination therapy with MUSE and sildenafil may be more efficacious in the salvage of patients who desire noninvasive therapy but in whom single-treatment modalities fail. Although both cAMP- and cGMP-mediated vasodilation can lead to penile erection, combining therapies that incorporate both pathways may succeed when single therapies fail.

Aged↗
PubMed2000

Cost-effectiveness of combination therapy for naive patients with chronic hepatitis C.

BACKGROUND/AIMS: The higher initial cost of combination therapy is a factor which may discourage its use in naive patients with histologically mild or moderate chronic hepatitis C. However, chronic hepatitis C is a slowly progressive disease associated with a decrease in life expectancy and quality of life. The objective of this study was to determine if the incremental sustained response rate of combination therapy is sufficient to outweigh its extra cost. METHODS: Chronic hepatitis C progression was studied using a Markov model in which cohorts of patients were treated with combination therapy for 6-12 months or with interferon for 12 months. The sustained virological response rates applied were 43, 35 and 19%, respectively, for combination therapy for 12 months, for 6 months and for interferon for 12 months. Costs for each clinical state were calculated according to clinical practice in Spain. RESULTS: In a 30-year-old patient with moderate chronic hepatitis C, combination therapy for 12 months increases life expectancy by 4.1 years compared with interferon for 12 months. In mild disease, the increase in life expectancy is lower. The cost per life-year saved in patients with chronic hepatitis C ranges from 880 to 64.421 euros depending on the age of the patient, the degree of hepatic lesion and the type and duration of therapy. Compared to other treatments accepted as standard practice in other therapeutic areas, combination therapy for chronic hepatitis C is cost-effective. CONCLUSIONS: In patients of any age with moderate chronic hepatitis C and those with mild disease under 50 years of age, combination therapy for 12 months is the most cost-effective schedule, whereas in older patients with mild hepatitis, combination therapy for 6 months is the preferred option based on cost-effectiveness criteria.

Adult↗
PubMed2000

Results from different patient populations using combined therapy with alprostadil and sildenafil: predictors of satisfaction.

OBJECTIVE: To evaluate the outcome of combined therapy (using intraurethral alprostadil and oral sildenafil) in private and clinic patients with erectile dysfunction, and thus assess predictors of satisfaction. PATIENTS AND METHODS: In all, 360 men were treated for erectile dysfunction using single and/or combined therapy, comprising 214 private-practice and 166 clinic patients. Responses were evaluated using the International Index for Erectile Function (IIEF) questionnaire before and after treatment. Serum testosterone levels, education and socio-economic status were also assessed. Group 1a consisted of 33 private patients and Group 1b of 24 clinic patients who tried the maximum dose of intraurethral alprostadil monotherapy initially, followed by the maximum dose of sildenafil monotherapy, and remained dissatisfied. Group 2a consisted of 32 private patients and group 2b of 31 clinic patients who tried the maximum dose of sildenafil monotherapy initially, followed by the maximum dose of alprostadil monotherapy, and were also dissatisfied. These two groups of 65 private and 55 clinic patients then underwent combined therapy. RESULTS: The mean (SD) score for erectile function was 24.1 (2) for combined therapy (a 123% improvement), and 19.8 (1. 8) (83% improvement) and 15.2 (1.6) (41% improvement) for sildenafil and alprostadil monotherapies (P < 0.05 for both patient groups). The men also reported an improvement in their satisfaction with intercourse. However, at 18 months, 60 of the 65 private patients but only 40 of the 55 clinic patients continued with combined therapy; thus, the discontinuation rate was three times greater among clinic than among private patients. Furthermore, the private patients had an overall improvement in the satisfaction score of 128%, compared with 51% for the clinic patients. CONCLUSION: Although there were no significant differences in erectile function improvement within the two satisfied combined therapy groups, the differences in overall satisfaction and long-term withdrawal rates suggests that other factors beside motivation must be involved for success, e.g. education, persistence, realistic expectations, and certain psychological factors. Combined therapy should be considered for those patients who have a suboptimal response to monotherapy and refuse or are not candidates for surgical options. Generally, those patients with a higher education, greater persistence and more realistic expectations were more satisfied with combined therapy.

Alprostadil↗
PubMed2005

Development of hepatocellular carcinoma after interferon therapy in chronic hepatitis C. Is it possible to reduce the incidence by ribanirin and IFN combination therapy?

OBJECTIVES: Although the incidence of hepatocellular carcinoma (HCC) has been shown to be reduced after interferon (IFN) monotherapy in chronic hepatitis C, the risk factors for the development of HCC have not been fully understood. The aim of this study is to investigate the risk factors for the development of HCC after IFN in chronic hepatitis C as well as whether the incidence of HCC will be reduced by ribavirin and IFN combination therapy or not. METHODS: 495 patients with chronic hepatitis C and which received IFN monotherapy were followed and the incidence and risk factors for the development of HCC were examined. On the other hand, in the patients which received ribavirin and IFN combination therapy, the sustained response rate was assessed and the reduction rate of HCC development was predicted. RESULTS: Multivariate analysis by the Cox proportional hazard model revealed that the risk factors for HCC development were age, male gender, severe fibrosis and outcome of IFN therapy. On ribavirin and IFN combination therapy, the sustained response rate reached 17.3% in genotype 1b and 74% in genotypes 2a and 2b infection, thus reducing 20% of the estimated incidence of HCC. CONCLUSION: To reduce the incidence of HCC in chronic hepatitis C, improvement of the sustained response rate is an essential issue, and ribavirin and IFN combination therapy shows to be promising.

Age Factors↗
PubMed2006

Clinical inquiries. What is the role of combination therapy (insulin plus oral medication) in type 2 diabetes?

Combination therapy using insulin plus metformin (Glucophage), a sulfonylurea, or both produces glycemic control comparable with using insulin alone, but there is less weight gain when metformin is used (strength of recommendation [SOR]: B, based on systematic review of randomized controlled trials [RCTs] with some heterogeneity). Combination therapy using insulin and pioglitazone (Actos) reduces glycosylated hemoglobin (Hb A1c) more than either insulin alone or adding pioglitazone to a sulfonylurea, but results in more weight gain (SOR: A, based on RCT). Using insulin glargine (Lantus) in combination therapy produces fewer nocturnal hypoglycemic events than using neutral protamine Hagedorn (NPH) insulin, while producing equivalent Hb A1c reduction (SOR: B, based on RCT). When the HbA1c is high (above 9.0% to 9.5%) on 1 or 2 oral agents, beginning combination therapy is more effective than adding another oral agent (SOR: B, based on subpopulation analysis in RCTs).

Diabetes Mellitus, Type 2↗
PubMed2006

Cost-effectiveness of hematologic growth factors for anemia occurring during hepatitis C combination therapy.

In hepatitis C virus (HCV)-infected patients who develop anemia during combination therapy, erythropoietic growth factors maintain higher drug treatment levels compared to ribavirin dose reduction, which may lead to an increase in treatment response rates. This study estimated the cost-effectiveness of growth factor therapy in maintaining anemic HCV-infected patients on target drug levels during combination therapy. A decision analysis using a Markov model was developed with 7 health states: Sustained viral response, chronic HCV, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, and death. Data sources included population-based studies of growth factor therapy, previously published estimates of costs and natural history of hepatitis C, and recent prospective studies. Our reference case was a 45-year-old Caucasian man with HCV infection (genotype 1, 2, or 3) who developed anemia while undergoing combination therapy with ribavirin and pegylated interferon. We compared growth factor injections (darbepoetin alpha or epoetin alpha) during combination therapy with standard ribavirin dose reduction. Compared to a ribavirin dose reduction strategy, the cost of darbepoetin per additional quality-adjusted life-year was 34,793 dollars for genotype 1 and 33,832 dollars for genotypes 2 or 3 versus 60,600 dollars and 64,311 dollars for epoetin. For all genotypes, the results were sensitive to changes in the cure rates of HCV therapy, the utility of chronic HCV, the costs of growth factors, and the age at which therapy is begun. In conclusion, use of erythropoietic growth factors, specifically darbepoetin, for patients with anemia occurring during HCV combination therapy appears to be cost-effective for genotypes 1, 2, or 3.

Anemia↗
PubMedDate not supplied

Recurrent ingrown toenails secondary to indinavir/ritonavir combination therapy.

OBJECTIVE: To report five cases of ingrown toenails (IGTN) associated with indinavir/ritonavir (IDV/RTV) combination therapy. CASE SUMMARY: The median onset of IGTN from initiation of IDV/RTV therapy was 18.4 weeks. Four patients previously received IDV, with one of these experiencing prior IGTN. All patients required surgical management of IGTN. All patients received virologic benefit from ongoing antiretroviral therapy, and the majority of patients elected to maintain IDV/RTV combination therapy. Two patients experienced recurrent IGTN while receiving ongoing IDV/RTV combination therapy. DISCUSSION: IGTN and paronychia have previously been reported with IDV and lamivudine. IGTN in patients with HIV infection is more likely to present acutely, involve more digits, and require surgical management IDV increases retinoic acid signaling and, based on elevated IDV concentrations from concomitant RTV therapy, the risk of IGTN may be increased in patients receiving IDV/RTV combination therapy. CONCLUSIONS: With the increasing popularity of IDV/RTV combination therapy, clinicians should be aware of the potential increase in frequency of dose-related toxicities including IGTN. Evaluation of hands and feet on physical examination should be recommended for all patients being treated with lamivudine and IDV, especially when used in combination with RTV.

Adult↗
PubMed2006

Relative efficacy of psychotherapy and combined therapy in the treatment of depression: a meta-analysis.

BACKGROUND: Reviews of the relative efficacy of psychotherapy and combined therapy (psychotherapy with pharmacotherapy) for depression have yielded contradicting conclusions. This may be explained by the clinical heterogeneity of the studies reviewed. AIMS: To conduct a meta-analysis with an acceptable level of homogeneity in order to investigate the relative efficacy of psychotherapy and combined therapy in the acute treatment of depression. METHOD: A systematic search was performed for RCTs published between 1980 and 2005 comparing psychotherapy and combined therapy in adult psychiatric outpatients with non-psychotic unipolar major depressive disorder. The studies were classified according to the chronicity and severity of the depression. Data were pooled by means of meta-analysis and statistical tests were conducted to measure heterogeneity. RESULTS: The meta-analysis included seven studies looking at a total of 903 patients. None of the heterogeneity tests established significance. This indicates a lack of evidence for the heterogeneity of the results. The dropout rates did not differ significantly between the two treatment modalities (25% in combined therapy and 24% in psychotherapy, p=0.77). At treatment termination, the intention-to-treat remission rate for combined therapy (46%) was better than for psychotherapy (34%) (p=0.0007); Relative Risk 1.32 (95% CI: 1.12-1.56), Odds Ratio 1.59 (95% CI: 1.22-2.09). In moderate depression, the difference between the remission rate for combined therapy and psychotherapy was statistically significant (47% compared to 34% respectively, p=0.001). This was not the case in mild major depression (42% compared to 37% respectively, p=0.29). The difference was also statistically significant in chronic major depression (48% compared to 32%, p<0.001), but not in non-chronic major depression (43% compared to 37%, p=0.22). On a more specific level, no differences were found in the remission rates for the treatment modalities in mild or moderate non-chronic depression. Combined therapy led to significantly better results than psychotherapy in moderate chronic depression only (48% compared to 32%, p<0.001). CONCLUSIONS: In the acute treatment of adult psychiatric outpatients with major depressive disorder, patient compliance with combined therapy matches compliance with psychotherapy alone. Combined therapy is more efficacious than psychotherapy alone. However, these results depend on severity and chronicity. Combined therapy outperformed psychotherapy in moderate chronic depression only. No differences were found in mild and moderate non-chronic depression. No data were found for mild chronic depression and for severe depression.

Chronic Disease↗
PubMed2000

Efficacy of a short-term ribavirin plus interferon alpha combination therapy followed by interferon alpha alone in previously untreated patients with chronic hepatitis C: a randomized multicenter trial.

BACKGROUND: Combination therapy with interferon alpha (IFNalpha) plus ribavirin has been shown to improve the sustained response rate in patients with chronic hepatitis C but there is little information regarding the lengths of time for this therapeutic regimen. In this study we therefore tried to evaluate whether the analysis of different virological parameters could provide new clues with respect to the early determination of the efficacy of this form of combination therapy. Furthermore, we also examined whether short-term induction combination therapy followed by IFNalpha alone is more effective than monotherapy in mounting an initial as well as a sustained virological response. METHODS: 185 patients with histologically proven chronic hepatitis C (mean age 42 years (range 19-65 years); 110 males, 75 females) were enrolled in the study. The patients were randomly assigned to receive, over the first 12 weeks, either interferon alpha 2a 6 million units (MU) three times weekly plus ribavirin 14 mg/kg per day (n=93) or the same dose of IFNalpha alone (n=92). Patients with a virological response (serum HCV RNA undetectable) after 12 weeks were subsequently treated with 3 MU IFNalpha alone thrice weekly for a further 40 weeks. Otherwise, treatment was discontinued. After the end of treatment, patients were followed up for 24 weeks. RESULTS: Patient characteristics at baseline were not significantly different in the two treatment groups. An initial virological response at week 12 was seen in 61 (66%) patients receiving IFNalpha plus ribavirin and in 44 (48%) being treated with IFNalpha alone (p=0.015) and this improvement in the response rate was mainly restricted to HCV genotype 1-infected patients (58% vs. 38%). In contrast, end-of-treatment (week 52) and sustained virological response rates were similar in both groups (37% vs. 29% and 26% vs. 17% [p=0.1], respectively). Interestingly, patients with HCV genotype 3, however, clearly benefited from short-term combination therapy. Thus, sustained virological response rates in these patients significantly increased from 25% (IFNalpha monotherapy) to 59% (combination therapy) (p=0.05). CONCLUSIONS: Short-term combined therapy for 12 weeks is more effective than the monotherapy with respect to the induction of an initial virological response but this effect applies only to genotype 1-infected patients. However, there is no significant difference between both therapeutic schedules with regard to the induction of sustained response. Although HCV genotype 3-infected patients seem to benefit from this short-term combined therapy, prolonged combined therapy may be necessary in HCV genotype 1-infected patients.

Adult↗
PubMed2001

[Weekly cyclophosphamide pulse therapy combined with corticosteroids in the treatment of pemphigus].

OBJECTIVE: To investigate the better regimen of combined cyclophosphamide pulse therapy with corticosteroids in the treatment of Pemphigus. METHODS: Intravenous cyclophosphamide was given weekly in a dosage of 600 mg to those Pemphigus patients whose conditions couldn't be improved by corticosteroids (oral prednisone 1.2-1.5 mg/kg/d) alone. RESULTS: Ten patients with Pemphigus received weekly cyclophosphamide therapy in addition to corticosteroid. Patients conditions improved quickly, without side effects. CONCLUSIONS: Cyclophosphamide weekly pulse therapy combined with corticosteroids is a good regimen in the treatment of Pemphigus.

Adrenal Cortex Hormones↗
PubMed2000

Combination therapy for acute myocardial infarction: fibrinolytic therapy and glycoprotein IIb/IIIa inhibition.

Reperfusion with a regimen of fibrinolytic therapy, aspirin, and unfractionated heparin is limited by a less than desirable reperfusion rate, an excessive reocclusion rate, a dose-limiting intracranial hemorrhage rate, and a competitive posture relative to direct coronary angioplasty. Only 50% to 60% of patients achieve early Thrombolysis in Myocardial Infarction grade 3 flow within 90 minutes with the most effective thrombolytic regimens. Even after initial reperfusion is achieved, transient and permanent reocclusion occurs too often and is associated with a high mortality rate. As more older patients are being treated, intracranial hemorrhage is becoming more common. Finally, the risk of bleeding and procedural failure has been high in patients who received an acute percutaneous interventional procedure shortly after treatment with fibrinolytic therapy. Early studies combining full-dose fibrinolytic treatment and glycoprotein IIb/IIIa inhibitors have been promising with regard to overcoming these limitations, but concern about bleeding has hindered this strategy. Several recent trials have evaluated full-dose abciximab with reduced-dose fibrinolytic therapy and have yielded promising results. The complementary nature of the results from different trials is striking, with substantial evidence that approximately half the conventional dose of fibrinolytic therapy combined with full-dose glycoprotein IIb/IIIa inhibition with abciximab achieves high rates of grade 3 flow and excellent clinical outcomes. This approach will now be tested in a large-scale mortality trial.

Abciximab↗
PubMed1988

Combination therapy with flutamide and castration (LHRH agonist or orchiectomy) in previously untreated patients with clinical stage D2 prostate cancer: today's therapy of choice.

One hundred and ninety-nine patients with clinical stage D2 prostate cancer who had not received previous endocrine therapy or chemotherapy were treated with the combination therapy using the pure antiandrogen Flutamide and the LHRH agonist [D-Trp6]LHRH ethylamide for an average of 26 months (3-59 months). The objective response to the treatment was assessed according to the criteria of the U.S. NPCP. There was a 5.7-fold increase (26.3 vs 4.6%) in the percentage of patients who achieved a complete response compared with the results obtained in five recent studies limited to removal (orchiectomy) or blockade (DES or Leuprolide) of testicular androgens. Only 12 of the 186 evaluable patients (6.5%) did not show an objective positive response at the start of the combination therapy compared with an average of 18% in the same five studies using monotherapy. The duration of response was also significantly improved in the patients who received the combination therapy while the death rate was decreased by approximately two-fold during the first 4 yr of treatment. In fact, while an approximately 50% death rate is observed at 2 yr in all studies using monotherapy, the same 50% death rate is delayed by 2 yr in the present study. It should be mentioned that at the time of relapse under combination therapy, the treatment is continued and, in addition, further blockade of adrenal androgen secretion is achieved with aminoglutethimide. The marked (5.7-fold) improvement in the rate of complete objective responses coupled with the three-fold decrease in the number of non-responders, the increased duration of the positive responses and the two-fold decrease in the death rate during the first 4 yr of treatment are obtained with the combination therapy using Flutamide and castration, thus improving the quality and duration of life with no or minimal side-effects. By blocking the androgen receptors in the prostatic cancer tissue, the antiandrogen decreases the action of the androgens of adrenal origin and thus inhibits the growth of a large number of tumors which, otherwise, would continue to be stimulated by the adrenal androgens left after medical or surgical castration.

Aged↗