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Biomedical subjects

H Heinzer

Publications and source records attributed to H Heinzer.

At least 19 recordsLinked to original sources
PubMed2006

Interleukin-2/interferon-alpha2a/13-retinoic acid-based chemoimmunotherapy in advanced renal cell carcinoma: results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

We performed a prospectively randomised clinical trial to compare the efficacy of four subcutaneous interleukin-2-(sc-IL-2) and sc interferon-alpha2a (sc-IFN-alpha2a)-based outpatient regimens in 379 patients with progressive metastatic renal cell carcinoma. Patients with lung metastases, an erythrocyte sedimentation rate < or =70 mm h(-1) and neutrophil counts < or =6000 microl(-1) (group I) were randomised to arm A: sc-IL-2, sc-IFN-alpha2a, peroral 13-cis-retinoic acid (po-13cRA) (n=78), or arm B: arm A plus inhaled-IL-2 (n=65). All others (group II) were randomised to arm C: arm A plus intravenous 5-fluorouracil (iv-5-FU) (n=116), or arm D: arm A plus po-Capecitabine (n=120). Median overall survival (OS) was 22 months (arm A; 3-year OS: 29.7%) and 18 months (arm B; 3-year OS: 29.2%) in group I, and 18 months (arm C; 3-year OS: 25.7%) and 16 months (arm D; 3-year OS: 32.6%) in group II. There were no statistically significant differences in OS, progression-free survival, and objective response between arms A and B, and between arms C and D, respectively. Given the known therapeutic efficacy of sc-IL-2/sc-INF-alpha2a/po-13cRA-based outpatient chemoimmunotherapies, our results did not establish survival advantages in favour of po-Capecitabine vs iv-5-FU, and in favour of short-term inhaled-IL-2 in patients with advanced renal cell carcinoma receiving systemic cytokines.

Adult↗
PubMed2006

[Success rates of two-layer, microsurgical vasovasostomy. Results from a patient questionnaire and comparison with one-layer technique].

UNLABELLED: Vasovasostomy is the most commonly performed procedures in the therapy for occlusive azoospermia after vasectomy. In our clinic the two-layer microsurgical technique (DL VVST) is considered to be the gold standard. We have examined the results of DL VVST by means of a questionnaire and compared them with those of the monolayer technique (ML VVST). MATERIALS AND METHOD: In the period from 1996 to 2001, a microsurgical DL VVST with 10 x 0 Prolene sutures under the operation microscope was performed in 141 patient. Aspects of the operation, social aspects and postoperative results (results of spermiogram, birth rates) were assessed by means of a questionnaire. The results were compared with those of a historical patient collective who had undergone a modified monolayer VVST with 7 x 0 Prolene (n = 64). RESULTS: The questionnaire could be sent to 90/141 patients, the response rate was 63/90 (70 %). The time interval between vasectomy and VVST was on average 9.5 years. The patency rate was 86 %, the birth rate 24 %. Severe or moderately sever complications did not occur. In the historical patient collective, the average occlusion interval was 6.9 years. The patency rate in these patients in whom the VVST was performed merely under the loupe and in a monolayer technique was 87 %, the pregnancy rate 48 %. CONCLUSION: The highly positive results of VVST with pregnancy rates > 80 % from earlier publications could not be reproduced. According to our results, the two-layer VVST does not afford better results than the monolayer technique.

Adult↗
PubMed2005

[Fast-track surgery in radical retropubic prostatectomy. First experiences with a comprehensive program to enhance postoperative convalescence].

Fast-track surgery is a comprehensive program for the optimization of perioperative care in elective surgery reducing potential postoperative complications and speeding up convalescence. Recent data from randomized colon resection trials emphasize that fast-track surgery is possible in most major operations. Our initial results in radical retropubic prostatectomy fast-track surgery have been encouraging. Fast-track surgery in major urological operations needs validation using randomized trials.

Clinical Trials as Topic↗
PubMed2004

Therapeutic approaches in metastatic renal cell carcinoma: local immunotherapy.

Since 1990, aerosol interleukin (IL)-2 has been used to treat pulmonary metastatic renal cell carcinoma (pmRCC). Inhalation therapy deposits a drug into the airways to achieve a high, local, clinical effect while avoiding serious systemic side effects. We report three studies to describe safety and efficacy of aerosol IL-2 in patients with pmRCC. In a multicenter study, 24 patients received exclusive inhalation (study I) of natural IL-2 (three dose levels, 48 weeks) and response and toxicity were evaluated. The survival of high-risk patients (study II) with mainly inhaled IL-2 (n=94) was compared with that of patients receiving systemic IL-2 (n=103). In ten patients we analyzed in detail lung function and markers of airway inflammation before and during inhalational IL-2 therapy (study III). Study I: The response of exclusive inhalation was 33.3% at 3 months and 16.7% at 6 months. Treatment was well tolerated, cough being the most frequent adverse event. Study II: The probabilities of survival at 5 years were 21% for the inhalational group and 0% for the systemic group. Study III: Inhaled IL-2 induced a moderate decline of forced expiratory volume (FEV), while exhaled nitric oxide (NO) and sputum eosinophils rose accompanied by moderate cough and dyspnea. In conclusion, inhalational IL-2 combines good efficacy and improves tolerability. This is especially important for patients who are not able to benefit from systemic IL-2 therapy. Whether the local eosinophilic response additionally supports the antitumor effect remains a challenging question.

Administration, Inhalation↗
PubMed2003

[Immunotherapy of renal cell carcinoma. With special emphasis on therapy of the elderly patient].

Interleukin-2 (IL-2) and/or interferon-alpha (IFN-alpha) induce remissions and prolong life in patients with metastatic renal cell carcinoma when carefully selected for a possibly toxic treatment. However, better-tolerated and more effective therapies are needed, especially in the elderly and patients with comorbidities. Recent achievements in the treatment of advanced renal cell carcinoma highlight potentially significant improvements. Immune cells within the tumor correlate with response and survival indicating the importance of local immune modulation. Such modulation has allowed introducing well-tolerated treatments such as inhalation of IL-2 to control lung metastases, which results in a significant survival benefit for high-risk patients as suggested by a recent cohort study in 200 patients. Antibody-based tumor targeting against cG250, specifically expressed on RCC, seems to stabilize progressive metastatic disease and does not induce toxicity. Vaccination strategies are also well tolerated, but have not shown convincing results in advanced disease so far. Other approaches have not fulfilled expectations. Stem cell transplantation still has significant toxicity and cannot be recommended for the elderly.

Administration, Inhalation↗
PubMed2003

Efficacy and safety of inhaled recombinant interleukin-2 in high-risk renal cell cancer patients compared with systemic interleukin-2: an outcome study.

Systemic IL-2 is an effective treatment for low to intermediate risk mRCC patients, its efficacy is marginal in high-risk cases. Therefore, other treatment approaches are required for this population. Ninety-four high-risk patients with RCC and pulmonary metastases were treated with inhaled plus concomitant low-dose subcutaneous rhIL-2. Clinical response, survival and safety were compared with those from IL-2 given systemically at the registered dose and schedule in 103 comparable historical controls. In the rhIL-2 INH group, treatment consisted of 6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily. The rhIL-2 SYS group received treatment which consisted of intravenous infusion of 18.0 MIU/m2/day rhIL-2 or SC injection of 3.6-18.0 MIU rhIL-2. Some patients in both groups also received IFNalpha. Mean treatment durations were 43 weeks rhIL-2 INH and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression-free survival durations were observed in the rhIL-2 INH group. The probability of survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5 years in the rhIL-2 SYS group. A multivariate analysis of overall survival adjusting for differences in baseline characteristics between the two treatment groups resulted in a risk ratio of 0.43 (95% CI 0.30-0.63; P < 0.0001). The data suggested an association between the response (SD or better) and survival, especially in the rhIL-2 INH group. The inhalation regimen was well tolerated. This outcome study suggests that administration of rhIL-2 by inhalation is efficacious and safe in high-risk mRCC patients with pulmonary metastases, who have no other treatment option available.

Administration, Inhalation↗
PubMed2002

[Immunotherapy of metastatic renal cell carcinoma in Germany. An assessment of the current status].

This survey was established to evaluate everyday use of interferon-alpha (IFN-alpha) and interleukin-2 (IL-2) in metastatic renal-cell carcinoma (mRCC). Of 186 centers (with 2200 patients per year) that responded, 182 support immunotherapy by using it themselves (147 centers) or by referring patients (35 centers). Effectiveness and tolerance are the main reasons for use. 133 centers use IL-2 subcutaneously, 64 by inhalation, 24 use it locally or intratumorally. Continuous intravenous IL-2 is used in 13 centers only. Most centers use subcutaneous combinations of IL-2 and IFN-alpha, either alone or with 5-fluorouracil and/or isotretinoin; IFN-alpha/Vinblastin combinations, IFN-alpha-monotherapy, and IL-2 s.c.-monotherapy are used with similar frequency. Average treatment duration is 3-6 months. Maintenance therapy is used in responding patients in 118 centers. Subcutaneous and local application of IL-2 is standard treatment for mRCC in Germany and subcutaneous IL-2 and IFN-alpha represents the most frequently used combination.

Antineoplastic Agents↗
PubMed2002

[Regional immunotherapy of metastatic renal cell carcinoma].

We summarized the current literature concerning regional immunotherapy of pulmonary metastases in metastatic renal cell carcinoma and other malignancies using inhaled interleukin-2 (IL-2). Inhaled IL-2 therapy is associated with minimal toxicity and is effective in preventing progression in metastatic renal cell carcinoma, melanoma, and possibly other diseases such as breast cancer. Local (physiologic) use and systemic (pharmacologic) use of IL-2 are not mutually exclusive; a combination may be very appropriate in metastatic cancer. Local physiologic therapy intensifies treatment without intensifying toxicity.

Administration, Inhalation↗
PubMed2001

[Side-fire laser coagulation of the prostate with the neodymium:YAG-laser. Long-term outcome].

Transurethral laser prostatectomy has been widely used in patients with benign prostatic obstruction (BPO) with good short-term results and an excellent safety profile. We investigated how stable the results of side-firing visual laser coagulation of the prostate are during long-term follow-up to evaluate whether laser prostatectomy can really be an alternative to transurethral resection of the prostate (TURP). Between January 1993 and December 1995 a total of 59 patients underwent visual transurethral side-firing laser coagulation of the prostate (Urolase, Bard Inc., Murray Hill, NJ, USA). The patients were monitored at 1, 3, 6, and 12 months and then reevaluated after a mean of 33 months. As expected, at the 1-year follow-up there was a significant improvement in peak flow rate, post-void residual urine, international prostate symptom score (IPSS) and quality of life index (QoL). After a mean of 33 months, 15% of the patients required reoperation due to persistent BPO. In the remaining patients, peak flow rate and post-void residual urine were stable. However, the QoL index increased during long-term follow-up and no longer differed from the preoperative value after 33 months. The side-firing laser coagulation of the prostate does not seem to be a sufficient therapeutic alternative to TURP in the treatment of BPO.

Aged↗
PubMed2001

Systemic chemotherapy and chemoimmunotherapy for metastatic renal cell cancer.

We review the current literature on systemic therapy for patients with metastatic renal cell carcinoma. Metastatic renal cell carcinoma remains highly resistant to chemotherapy and hormonal agents not justifying its use as a single agent. Interleukin-2 immunotherapy is the most effective treatment for metastatic renal cell carcinoma available today. There is evidence that interleukin-2 improves survival and yields long-lasting remissions in selected patients; the optimal dose and schedule still need to be defined. Response rates in patients treated with subcutaneous interleukin-2 are similar to those achieved with high-dose bolus intravenous applications. Questions remain concerning quality of life and benefit-to-risk ratio with respect to immunotherapy in individual patients. Different routes of administration of interleukin-2 such as local application, promise to improve quality of life and survival times.

Antineoplastic Agents↗
PubMed2000

[Treatment of metastatic renal cell carcinoma. Value of immunotherapy compared with surgery of metastases].

The prognosis for patients in whom metastatic renal cell carcinoma (RCC) is not treated is unfavorable, with a reported 5-year survival of 0-18%. Before the era of immunotherapy and in the absence of effective nonsurgical therapy, resection of metastases was the accepted way to prolong survival, giving a 5-year survival of 7-69%. Retrospective studies have shown that several clinical factors are associated with a relatively good prognosis. Some patients will benefit from resection of metastases, but most patients with metastatic RCC are not candidates for such aggressive surgery. The use of interleukin-2 has demonstrated that immunotherapy can produce durable remissions. Without randomized trials, it is difficult to know whether survival is longer than that in untreated patients, but there is clear evidence that immunotherapy improves survival and yields long-lasting remissions in selected patients. Many questions remain concerning quality of life and the benefit-to-risk ratio of immunotherapy, but it is the most effective treatment for metastatic RCC.

Carcinoma, Renal Cell↗
PubMed2000

A comparison of systemic versus inhaled recombinant IL-2 administration for the treatment of metastatic renal cell carcinoma.

The aim of the current study was to compare the objective response and survival rates of patients with mRCC treated with IL-2 administered either systemically (SYST, subcutaneously) or via inhalation (INH), using relatively large sample sizes to afford a more meaningful comparison. We used univariate and multivariate analyses to retrospectively evaluate the data from two different databases generated from 277 patients treated with IL-2 during the 1993-1997 period, one developed at the University Hospital Hamburg-Eppendorf, and the other at Chiron-Amsterdam. Patients treated with INH IL-2 tended to have a poorer ECOG performance status than patients receiving SYST IL-2. Of 75 patients receiving INH IL-2, eight (10.7%) achieved an objective response; of 202 patients administered SYST IL-2, 45 (22.2%) achieved an objective response. The median survival time was 13.8 months for patients receiving INH IL-2 and 13.1 months for patients treated with SYST IL-2. One- and two-year survival rates were also comparable for the two treatment modalities (one-year: INH, 55%; SYST, 56%; two-year: INH, 28%; SYST, 26%). There was no significant difference in the likelihood of survival for patients receiving INH IL-2 versus SYST IL-2 (risk ratio = 0.82, P = 0.27). Patients administered INH IL-2 experienced considerably less toxicity and complications than patients administered SYST IL-2. We conclude that INH IL-2 treatment is at least as effective as SYST IL-2 treatment in promoting the survival of patients with mRCC. Given that INH IL-2 treatment of patients with a poorer ECOG performance status elicited a survival rate comparable to that seen with SYST IL-2 treatment of patients with a superior performance status, the potential exists for INH IL-2 treatment to be even more effective for patients having a better performance status. Additionally, INH IL-2 treatment is considerably less toxic and associated with fewer complications than SYST IL-2 treatment, thus providing a therapeutic option for otherwise untreatable patients, offering patients a relatively good quality of life, and requiring fewer co-medications. Nonetheless, selection of an IL-2 treatment modality should be based on several patient-related considerations. Moreover, these two IL-2 treatment modalities need not be mutually exclusive.

Administration, Inhalation↗
PubMed2000

Overview of interleukin-2 inhalation therapy.

PURPOSE: Locoregional administration of interleukin (IL)-2, which acts physiologically as a local hormone, is an effective therapeutic modality. Diverse preclinical and clinical models have described methods of administration that expose tumor tissues to continuously high levels of cytokines. Regional administration of IL-2 that does not raise intravascular IL-2 levels induces local and systemic immunomodulation and produces objective local tumor responses. Most importantly, regional therapy is much less toxic than systemic IL-2 therapy. PATIENTS AND METHODS: We review clinical experiences using inhaled IL-2 therapy for the treatment of pulmonary metastases in roughly 300 patients with a variety of primary tumors. This includes our own 10-year single-institution experience with inhaled IL-2 therapy in the treatment of 188 metastatic renal cell carcinoma patients with progressive pulmonary metastases. Patients in our clinic are treated with 18 to 36 million IU of recombinant IL-2, administered 90% by inhalation and 10% subcutaneously, until disease progression. A variety of doses and schedules of inhaled IL-2 have been investigated alone and in combination with systemic therapies. RESULTS: Inhalation of IL-2 has been reported to prevent progression of pulmonary and mediastinal metastases of metastatic renal cell carcinoma, breast and ovarian carcinoma, and melanoma. Inhaled IL-2 alone is well tolerated; a dose-dependent cough is the major adverse event. A significant dose-dependent increase in lymphocytes and eosinophils has been observed in bronchoalveolar lavage in patients and animals. Dose and schedule can influence outcome. In a phase I trial using inhaled IL-2 alone in patients with a variety of primary malignancies, once-daily inhalation of IL-2 at doses up to 15 million IU/m2 was well tolerated but did not result in prolonged stabilization of pulmonary disease. In a multidose phase I trial, using 5-times-daily inhalation of natural IL-2, pulmonary lesions in three of 14 (21%) metastatic renal cell carcinoma patients responded, and a similar multicenter trial demonstrated a 29% response rate. Among 188 metastatic renal cell carcinoma patients treated with inhaled recombinant IL-2 at the Clinic Eppendorf, progression of pulmonary metastases was prevented in 68% of patients for a median duration of 7 months, and overall survival was significantly improved compared with expected survival (Elson's risk analysis; 17.2 vs 5.3 mo). All patients, including high-risk patients, appeared to benefit. Encouraging results have also been reported in patients with metastatic melanoma and gynecologic tumors when inhaled IL-2 was used as second-line therapy to treat pulmonary metastases. CONCLUSIONS: The efficacy of inhaled IL-2, alone or in combination with systemic immunotherapy, immunochemotherapy, or chemotherapy, has been documented in a variety of malignancies. All reports confirm low toxicity, thus providing important quality-of-life benefits. Moreover, patients not eligible for systemic IL-2 therapy may be treated with inhalation therapy.

Administration, Inhalation↗
PubMed1999

[Treatment of pulmonary metastases from kidney cell carcinoma with inhalational interleukin-2. 10-year experience Hamburger Unicenter].

Systemic immunotherapy, notably with interleukin-2 (IL-2) and interferon-alpha (IFNalpha), has yielded a response rate of 10 % to 30 % in metastatic renal cell carcinoma. However, systemic immunotherapy is limited by severe side effects, and long-lasting response is rare. Tumor palliation and quality-of-life are important end points for evaluating the clinical benefits of immunotherapy. Experimental and clinical treatment models have proved that local IL-2 application is less toxic than systemic treatment and is therapeutically effective. Here we report long-term experience with inhalation IL-2 therapy in 188 patients who had progressive pulmonary metastatic renal cell carcinoma. High-dose inhalation of IL-2 was used with low-dose systemic IL-2 or IFNalpha. Maximal toxicity over the total treatment time was mild, and the low incidence of WHO grade 3 toxicity (24 %) allowed social activities and performance of social roles. Comedication for systemic side effects was required only in half of the patients. Inhaled IL-2 prevented progress of pulmonary metastases in 68 % of patients for a median period of 9.8 months. Median survival was 12.4 months compared with the expected 5.3 months and quality-of-life did not differ substantially from pretreatment status. Local treatment can be applied alone or in combination with systemic therapy and can increase therapeutic efficacy.

Administration, Inhalation↗
PubMed1999

Subjective and objective prospective, long-term analysis of quality of life during inhaled interleukin-2 immunotherapy.

PURPOSE: We conducted both a subjective and objective, prospective quality-of-life analysis during high-dose (36 x 10(6) immunizing units/d) inhalational interleukin (IL)-2 treatment (mean treatment time, 13.4 months) of 15 patients with metastatic renal cell carcinoma (mRCC). Additionally, quality of life for 10 patients with mRCC receiving low-dose (9 x 10(6) IU/m(2)/d for 5 days) intravenous IL-2 treatment also was evaluated. PATIENTS AND METHODS: Patients responded to the European Organization for Research and Treatment of Cancer quality-of-life questionnaire QLQ-C30 before and during inhalational IL-2 treatment at 1, 3, 6, 9, and 12 months and before and once during intravenous IL-2 treatment. A clinician assessed patient well-being using the Quality of Well-Being scale to calculate once weekly quality-adjusted life-years (QALYs) during inhalational IL-2 treatment. RESULTS: Patients completed 103 questionnaires and clinicians performed 892 QALY calculations. For patients treated with inhalational IL-2, the mean quality-of-life score deteriorated modestly but significantly 1 month after treatment initiation (15.1%, P =.01) but did not differ significantly from pretreatment scores after 3, 6, 9, and 12 months of treatment. Inhalational IL-2 therapy stabilized patient quality of life for a mean of 13.4 months. The resulting QALY calculation for patients on inhalation IL-2 was 70.1% of 13.4 months, representing 9.4 months of QALY. In comparison, patients who received intravenous IL-2 showed a more marked, statistically significant deterioration in mean quality-of-life score during treatment (27%, P =.006); moreover, three of these 10 patients experienced treatment-related toxicity that prevented questionnaire completion. CONCLUSION: Quality-of-life analysis during immunotherapy provides valuable information regarding cancer treatment outcomes.

Activities of Daily Living↗