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1.
Phys Rev E ; 109(5-2): 055203, 2024 May.
Article in English | MEDLINE | ID: mdl-38907424

ABSTRACT

We show in experiments that a long, underdense, relativistic proton bunch propagating in plasma undergoes the oblique instability, which we observe as filamentation. We determine a threshold value for the ratio between the bunch transverse size and plasma skin depth for the instability to occur. At the threshold, the outcome of the experiment alternates between filamentation and self-modulation instability (evidenced by longitudinal modulation into microbunches). Time-resolved images of the bunch density distribution reveal that filamentation grows to an observable level late along the bunch, confirming the spatiotemporal nature of the instability. We provide a rough estimate of the amplitude of the magnetic field generated in the plasma by the instability and show that the associated magnetic energy increases with plasma density.

2.
Ann Oncol ; 21(9): 1804-1809, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20150572

ABSTRACT

BACKGROUND: Bevacizumab, the anti-vascular endothelial growth factor agent, provides clinical benefit when combined with platinum-based chemotherapy in first-line advanced non-small-cell lung cancer. We report the final overall survival (OS) analysis from the phase III AVAiL trial. PATIENTS AND METHODS: Patients (n = 1043) received cisplatin 80 mg/m(2) and gemcitabine 1250 mg/m(2) for up to six cycles plus bevacizumab 7.5 mg/kg (n = 345), bevacizumab 15 mg/kg (n = 351) or placebo (n = 347) every 3 weeks until progression. Primary end point was progression-free survival (PFS); OS was a secondary end point. RESULTS: Significant PFS prolongation with bevacizumab compared with placebo was maintained with longer follow-up {hazard ratio (HR) [95% confidence interval (CI)] 0.75 (0.64-0.87), P = 0.0003 and 0.85 (0.73-1.00), P = 0.0456} for the 7.5 and 15 mg/kg groups, respectively. Median OS was >13 months in all treatment groups; nevertheless, OS was not significantly increased with bevacizumab [HR (95% CI) 0.93 (0.78-1.11), P = 0.420 and 1.03 (0.86-1.23), P = 0.761] for the 7.5 and 15 mg/kg groups, respectively, versus placebo. Most patients ( approximately 62%) received multiple lines of poststudy treatment. Updated safety results are consistent with those previously reported. CONCLUSIONS: Final analysis of AVAiL confirms the efficacy of bevacizumab when combined with cisplatin-gemcitabine. The PFS benefit did not translate into a significant OS benefit, possibly due to high use of efficacious second-line therapies.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized , Bevacizumab , Carcinoma, Adenosquamous/drug therapy , Carcinoma, Adenosquamous/mortality , Carcinoma, Adenosquamous/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Humans , Lung Neoplasms/pathology , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Placebos , Prognosis , Survival Rate , Gemcitabine
3.
Eur Respir J ; 27(6): 1183-9, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16481389

ABSTRACT

The present prospective multicentre trial investigated whether topotecan, given at a starting dose of 1.25 mg.m(-2) with individual dose adjustment, can improve safety in patients with relapsed/refractory small cell lung cancer without loss of efficacy. Patients received topotecan intravenously on days 1-5, every 21 days, for up to six courses. In the absence of relevant haematotoxicities, topotecan was increased to 1.5 mg.m(-2) and reduced to 1.0 mg.m(-2) in case of severe haematotoxicities. Of 170 recruited patients, 73.2% had stage IV disease and 63.4% had platinum-containing pre-treatment. Patients received a total of 521 courses. In 72.6% of those courses, the dose remained at 1.25 mg.m(-2); in 9.1% it was reduced and in 18.3% it increased. Overall response rate was 14.1% including one complete response; 28.8% had stable disease. Median duration of response was 13.6 weeks and median survival was 23.4 weeks. Clinical benefit was obvious for sensitive as well as for refractory patients. Haematotoxicity of grade 3 or 4 was clearly lower compared with the standard dose of 1.5 mg.m(-2). In conclusion, topotecan at a dose of 1.25 mg.m(-2) appears to be as effective as the dose of 1.5 mg.m(-2), but with reduced toxicity. Since patients with recurrent small cell lung cancer have a poor prognosis, they benefit especially from good tolerability.


Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Small Cell/drug therapy , Lung Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Topotecan/administration & dosage , Aged , Antineoplastic Agents/toxicity , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/toxicity , Carcinoma, Small Cell/mortality , Carcinoma, Small Cell/pathology , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Resistance, Neoplasm , Female , Follow-Up Studies , Humans , Leukocyte Count , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Neutropenia/chemically induced , Neutrophils/drug effects , Organoplatinum Compounds/therapeutic use , Organoplatinum Compounds/toxicity , Platelet Count , Retreatment , Survival Rate , Topotecan/toxicity , Treatment Outcome
4.
Z Gastroenterol ; 43(2): 149-54, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15700204

ABSTRACT

INTRODUCTION: Epidemiological data of colorectal cancer are sparse and often incomplete. Therefore, we initiated a population-based examination of five-year survival of colorectal cancer patients. METHODS: For complete registration, diagnosis and tumour stage of all patients in the region of Bonn/Rhine-Sieg were assessed independently according to reports of medical practitioners and pathologists. Each patient was followed by a standardised questionnaire during a period of five years. RESULTS: Between June and November, 1994 348 patients were registered. Median age at diagnosis was 69 years for males (n = 160) and 72 years for females (n = 188). According to the UICC classification 18, 26, 23 and 26 % had stage I-IV tumours, respectively; the tumour stage remained unclear in 7 %. Adjuvant (radio)-chemotherapy was indicated in 89 patients, but only 49 % of these were treated. Five-year overall survival (OS) and relative overall survival were 41 and 54 %, respectively. Although disease-free survival (DFS) was significantly better for early stage colorectal cancer, OS did not differ significantly between stage I and stage III tumours. Young patients diagnosed before the age of 50 had a significantly lower DFS. These data were comparable with other European countries but were lower than data reported in the USA. DISCUSSION: The high rate of patients with stage IV colorectal cancer and the low proportion of patients receiving adjuvant (radio)-chemotherapy according to international or national consensus recommendations were disappointing. Although data were comparable with other European countries more efforts are necessary to establish effective screening programs for asymptomatic patients and to increase the willingness for standardised adjuvant treatment.


Subject(s)
Colorectal Neoplasms/mortality , Registries/statistics & numerical data , Adult , Age Factors , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Colectomy , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , Combined Modality Therapy/mortality , Disease-Free Survival , Female , Germany , Humans , Male , Middle Aged , Neoplasm Staging , Radiotherapy, Adjuvant , Survival Analysis
5.
Ann Oncol ; 14(10): 1570-7, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14504060

ABSTRACT

BACKGROUND: Although all first-generation 5-HT(3) receptor antagonists demonstrate efficacy in preventing acute chemotherapy-induced nausea and vomiting (CINV), effective prevention of delayed CINV has not yet been achieved. This study compared the efficacy and tolerability of palonosetron, a novel, second-generation 5-HT(3) receptor antagonist, with ondansetron. PATIENTS AND METHODS: In this multicenter, randomized, double-blind, stratified, phase III study, 570 adult cancer patients were randomized to receive a single i.v. dose of palonosetron 0.25 mg, palonosetron 0.75 mg or ondansetron 32 mg, each administered 30 min before initiation of moderately emetogenic chemotherapy. The primary end point was the proportion of patients with no emetic episodes and no rescue medication [complete response (CR)] during the 24 h after chemotherapy administration (acute period). Secondary end points included efficacy in treatment of delayed CINV (

Subject(s)
Antiemetics/therapeutic use , Antineoplastic Agents/adverse effects , Isoquinolines/therapeutic use , Nausea/chemically induced , Nausea/prevention & control , Ondansetron/therapeutic use , Quinuclidines/therapeutic use , Vomiting/chemically induced , Vomiting/prevention & control , Adult , Aged , Antiemetics/adverse effects , Antiemetics/pharmacology , Double-Blind Method , Female , Humans , Infusions, Intravenous , Isoquinolines/adverse effects , Isoquinolines/pharmacology , Male , Middle Aged , Ondansetron/adverse effects , Ondansetron/pharmacology , Palonosetron , Quinuclidines/adverse effects , Quinuclidines/pharmacology
7.
Eur J Cancer ; 38(13): 1739-46, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12175690

ABSTRACT

Cladribine (2-chlorodeoxyadenosine) (2-CdA) has been shown to be effective in mantle-cell (MCL) and low-grade lymphomas (lgNHL). The aim of this multicentre study was to evaluate the rate and duration of remissions and to examine the toxicity of the combination of reduced-dose 2-CdA and mitoxantrone (CdM) in MCL and lgNHL as first-line therapy or for patients in their relapse. A total of 285 courses, median of five courses per patient, were administered to 62 evaluable patients (42 previously untreated, 20 relapsed) with 5 mg/m(2) 2-CdA per day given as an intermittent 2-h infusion over 3 consecutive days combined with 8 mg/m(2) mitoxantrone on days 1 and 2 for the untreated patients or 12 mg/m(2) mitoxantrone on day 1 for patients in their first relapse for a maximum of six cycles every four weeks. 32 follicular, 18 MCL, 9 lymphoplasmacytoid, 2 marginal zone and 1 unclassified low-grade B-cell lymphoma were involved in the study. 56 of the 62 patients responded to CdM resulting in an overall response rate of 90% (95% confidence interval (CI), 80-96%) with a complete remission (CR) rate of 44% (95% CI, 31-57%) and a median duration of remission of 25 months (range 6-42+). The overall survival rate at 48 months was 80%. For 42 previously untreated patients, the overall response rate was 88% (95% CI, 74-96%) with a CR rate of 38% (95% CI, 24-54%), whereas the response rate for the group of 20 previously treated patients was similar with a 95% overall response (95% CI, 75-100%) and a CR rate of 55% (95% CI, 32-77%). In MCL, CdM showed a high activity, achieving a response rate of 100% (95% CI, 81-100%) with a CR rate of 44% and a median duration of remission of 24 months (range 6-35+). Myelosuppression was the major toxicity with 23% grade 3 granulocytopenia and 50% grade 4. Thrombocytopenia was less commonly observed, with only 8% grades 3 and 4. These results demonstrate that the combination of reduced-dose 2-CdA and mitoxantrone is a highly active regimen in the treatment of low-grade lymphomas, and in particular of MCL.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Mantle-Cell/drug therapy , Lymphoma, Non-Hodgkin/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cladribine/administration & dosage , Cladribine/adverse effects , Disease-Free Survival , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Mitoxantrone/administration & dosage , Mitoxantrone/adverse effects , Prospective Studies , Treatment Outcome
9.
Anticancer Res ; 19(4A): 2421-5, 1999.
Article in English | MEDLINE | ID: mdl-10470169

ABSTRACT

Human chorionic gonadotropin (HCG) is expressed in germ cell tumors and urothelial, breast, lung and colon cancers. The aim of the study was to investigate if the determination of HCG in comparison with CEA is able to discriminate between malignant and benign effusions. Effusion and partially serum samples of 61 patients with benign (g.i., heart/kidney isnuff.) and 116 patients with malignant diseases (g.i., gynec., lung, misc., CUP) were investigated. HCG was specifically determined by an IRMA using 2 monoclonal antibodies, CEA by a conventional double Ab RIA. Cytological staining was preformed using the Pappenheim-method on cytospin preparations. Significant differences (p < 0.001) were found for HCG between benign and malignant ascitic effusions with the best discrimination at 5 IU/l (ROC) and an overall sensitivity of 31.3% (spec. vs benign eff. 93.4%) increasing in subgroups from hematol. (5.8%) < misc. (31.3%) < gynec. (32.1%) < g.i. (36%) < lung (38.1%) to CUP (50%). CEA also showed significant differences between benign and malignant total and ascitic effusions, and weaker for the pleural subgroup (cutoff 9 ng/ml) with a total sensitivity of 44.6% (sp = 100%) increasing from misc. (30.8%) < lung (47.1%) < CUP (50%) < gynec. (60%) < g.i. (60.9%). Comparative cytology and TM determinations increased the positiverate of cytology (45.2%) to 58.3% for either cytology or HCG positive cases, or to 61.6% for either cytology or CEA positive cases. For the combined determination of cytologoy and HCG and CEA, the overall TM positive rate for 33 cytology-pos. cases was 78.8%, but in 40 cytology-negative cases 37.5% for TM positive cases. In conclusion HCG is useful in ascitic > pleural effusions with high specificity (90% at 5 IU/l) but low sensitivity of 31% increasing in g.i., lung and gynecologic cases, CEA a more general TM with higher sensitivity of 45% increasing in g.i., gynecologic and lung cases (sp. 100% at 9 ng/ml) both adding significantly to cytology-negative effusions.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoembryonic Antigen/analysis , Chorionic Gonadotropin/analysis , Exudates and Transudates/chemistry , Neoplasms/diagnosis , Biomarkers, Tumor/blood , Carcinoembryonic Antigen/blood , Chorionic Gonadotropin/blood , Diagnosis, Differential , Female , Gastrointestinal Diseases/blood , Gastrointestinal Diseases/diagnosis , Humans , Kidney Diseases/blood , Kidney Diseases/diagnosis , Male , Neoplasms/blood , Neoplasms/physiopathology , ROC Curve , Sensitivity and Specificity
10.
Diabetes Educ ; 25(1): 31-40, 1999.
Article in English | MEDLINE | ID: mdl-10232178

ABSTRACT

PURPOSE: This study examined the metabolic trend and factors associated with an unexpected rise in HbA1c levels during the summer, with a return to baseline when school resumed, in 40 intensively treated adolescents with type 1 diabetes. METHODS: Psychosocial data were collected using a variety of diabetes evaluation instruments. HbA1c was measured monthly. RESULTS: HbA1c values increased by a mean of .73% from May to July and decreased by a mean of .75% from August to October. Lack of consistency in summer routines compared with school days was associated with a worsening in metabolic control during the summer months. Other factors associated with the summer increase in HbA1c included lower guidance scores on the Diabetes Family Behavior Scale, and higher impact and worry scores on the Diabetes Quality of Life for Youth Scale. CONCLUSIONS: Interviews suggested that teenagers need to take a vacation from intensive diabetes care during the summer.


Subject(s)
Adolescent Behavior/psychology , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 1/psychology , Glycated Hemoglobin/analysis , Seasons , Adolescent , Adult , Child , Female , Health Knowledge, Attitudes, Practice , Humans , Leisure Activities/psychology , Male , Quality of Life , Surveys and Questionnaires
11.
Hybridoma ; 18(1): 87-91, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10211794

ABSTRACT

Nonresectable colorectal cancer metastases in the liver respond to chemotherapy in 20-25% only. Early identification of nonresponders might allow the use of other regimens. In a limited feasibility study, it should be determined whether (a) a single high-dose chemotherapy application has an early effect on glucose-utilization, detectable and quantitatable by noninvasive positron emission tomography using [18F]-Fluoro-deoxyglucose (FDG-PET) and (b) assess its value as a predictor of the final therapeutic outcome. A total of 10 patients with documented nonresectable liver metastases of a colorectal cancer were studied by FDG-PET, prior and 72 h after a single infusion of 5-Fluorouracil and Folinic acid (5-FU/FA). Glucose utilization was quantitated by determination of standard-uptake values and correlated with final therapy outcome following completion of the anticipated therapy cycle. Patients were followed up for at least 6 months. All metastases responding to therapy (n = 6) exerted a statistically significant decrease of FDG uptake (-22+/-10%), metastases (n = 2) showing a short-term effect (duration of tumor reduction <3 months) had a slightly diminished, and progressing metastases (n = 3) an enhanced FDG uptake (13+/-17%). Our preliminary data indicate that acute changes of glucose utilization-as detected by FDG-PET-following a single application of chemotherapy, seems to be indicative for the final therapeutic outcome, at least in liver metastases of colorectal cancer.


Subject(s)
Adenocarcinoma/drug therapy , Colorectal Neoplasms/drug therapy , Fluorodeoxyglucose F18 , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Tomography, Emission-Computed/methods , Adenocarcinoma/pathology , Adenocarcinoma/secondary , Aged , Animals , Antimetabolites, Antineoplastic/administration & dosage , Colorectal Neoplasms/pathology , Feasibility Studies , Female , Fluorodeoxyglucose F18/administration & dosage , Fluorodeoxyglucose F18/pharmacokinetics , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Male , Middle Aged , Predictive Value of Tests , Radiopharmaceuticals/administration & dosage , Radiopharmaceuticals/pharmacokinetics , Treatment Outcome
12.
J Assoc Nurses AIDS Care ; 9(5): 47-52, 1998.
Article in English | MEDLINE | ID: mdl-9742480

ABSTRACT

To better understand factors associated with symptomatic and asymptomatic vulvovaginal candidiasis, including the role of immune compromise and patient self-report, a cross-sectional analysis of factors associated with the isolation of yeast from vaginal swabs and clinical diagnosis of Candida vaginitis (CV) among 184 HIV-infected women was conducted. Sixty-four (35%) of the women had vaginal swabs positive for yeast. Nineteen (10%) women met the case definition for CV. In a logistic regression model, only CD4 < or = 100 cells/mm3 was predictive of CV (adds ratio = 4.5; 95% confidence interval = 1.0, 20; p = .05). The predictive value of patient self-report of CV was only 12%. This study demonstrates that all HIV-infected women should receive a regular and thorough gynecologic evaluation, regardless of self-reported symptoms. HIV-infected women will benefit from education about prevention and treatment of CV, and women whose CD4 counts are low may wish to consider prophylaxis for CV.


Subject(s)
AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/nursing , Candidiasis, Vulvovaginal/diagnosis , Candidiasis, Vulvovaginal/nursing , AIDS-Related Opportunistic Infections/immunology , AIDS-Related Opportunistic Infections/prevention & control , Adult , Age Factors , CD4 Lymphocyte Count , Candidiasis, Vulvovaginal/immunology , Candidiasis, Vulvovaginal/prevention & control , Cross-Sectional Studies , Female , Humans , Logistic Models , Middle Aged , Odds Ratio , Predictive Value of Tests , Women's Health
13.
Leukemia ; 12(9): 1338-43, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9737680

ABSTRACT

The efficacy of antifungal prophylaxis with itraconazole capsules and its serum concentrations were evaluated in patients intensively treated for acute leukaemia. A consecutive group of patients without systemic antifungal prophylaxis (January 1993 to August 1994, period 1) was compared with another consecutive group of patients (period 2) who received itraconazole capsules (September 1994 to April 1995 400 mg/day, from May 1995 onwards 600 mg/day). All patients admitted with acute leukaemia and standard or high-dose chemotherapy were included into the study. Clinical endpoint was mortality from proven fungal infection. Seventy-six patients and 148 courses of cytotoxic chemotherapy were analysed in the control group as well as 47 patients and 112 treatment courses in the intervention group. Antifungal prophylaxis led to a significant decrease of mortality from invasive fungal infections (8.8%-0.9%, P = 0.005). The median trough concentration of itraconazole of all measurements was 520 ng/ml (range 230-793) in patients who received 400 mg/day and 760 ng/ml (370-1200) in patients receiving a dosage of 600 mg/day (P = 0.002). These findings suggest that itraconazole is an effective drug for antifungal prophylaxis but also that a considerable number of patients do not reach the desired trough levels (>500 ng/ml) with itraconazole capsules.


Subject(s)
Antifungal Agents/therapeutic use , Itraconazole/therapeutic use , Mycoses/prevention & control , Neutropenia/complications , Acute Disease , Adult , Aged , Aged, 80 and over , Antifungal Agents/blood , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Drug Monitoring , Female , Humans , Itraconazole/blood , Leukemia/blood , Leukemia/drug therapy , Male , Middle Aged , Neutropenia/chemically induced , Prospective Studies
14.
J Urol ; 159(6): 1942-6, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9598493

ABSTRACT

PURPOSE: We evaluate the use of pretreatment follicle-stimulating hormone (FSH) in patients with germ cell tumors as a prognostic serum marker of spermatogenesis after standard treatment. Additionally, Leydig cell function was investigated by estimation of luteinizing hormone (LH) and testosterone (T), and calculation of the T/LH ratio. MATERIALS AND METHODS: Serum FSH, LH and T were determined radioimmunologically associated with semen analyses in 20 patients with seminoma (pathological stages IA to IIB) after unilateral orchiectomy before and up to 24 months after infradiaphragmatic radiotherapy. Additionally, hormone analyses were performed in 18 patients with nonseminomatous germ cell tumor (pathological stages IIA to C) before and up to 36 months after standard cisplatin based chemotherapy. RESULTS: Seminoma patients undergoing radiotherapy were divided into 2 groups consisting of 12 patients with normal pretreatment serum FSH and 8 with elevated FSH reflecting spermatogenesis deficits even before treatment. Six months after irradiation a significant increase in FSH (p <0.01) associated with a decrease in sperm density was observed in both groups and 24 months after radiotherapy patients with initially normal FSH had significantly lower serum FSH (p <0.01) associated with higher sperm density than those with initially elevated FSH (p <0.01), indicating less impairment of Sertoli cell function. Comparable results were observed in chemotherapy treated germ cell tumor patients with initially normal (11) and elevated serum FSH (7), respectively, and 36 months after chemotherapy patients with initially normal FSH had significantly lower FSH concentrations than those with initially elevated FSH (p <0.01). Compensated impairment of Leydig cell function reflected by a subnormal T/LH ratio was evident before chemotherapy in 16.7% of patients increasing up to 41.2% 36 months after therapy. In contrast, 24 months after radiotherapy only 25% of seminoma patients showed a subnormal ratio reflecting less damage to the Leydig cells caused by irradiation. CONCLUSIONS: Pretreatment FSH is a prognostic serum marker of spermatogenesis status of germ cell tumor patients receiving standard radiotherapy or chemotherapy. In contrast to seminoma patients after radiotherapy, impairment of Leydig cell function was evident in germ cell tumor patients after cisplatin based chemotherapy.


Subject(s)
Biomarkers, Tumor/blood , Follicle Stimulating Hormone/blood , Seminoma/blood , Spermatogenesis , Testicular Neoplasms/blood , Adult , Humans , Immunoradiometric Assay , Leydig Cells/physiology , Luteinizing Hormone/blood , Male , Orchiectomy , Prognosis , Seminoma/drug therapy , Seminoma/physiopathology , Seminoma/radiotherapy , Testicular Neoplasms/drug therapy , Testicular Neoplasms/physiopathology , Testicular Neoplasms/radiotherapy , Testosterone/blood
15.
Support Care Cancer ; 5(5): 387-95, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9322351

ABSTRACT

There is still controversy as to what constitutes the optimal therapy for acute and delayed chemotherapy-induced emesis and nausea. We conducted a three-armed randomized multi-centre study in 193 chemotherapy-naive patients receiving highly emetogenic chemotherapy inducing both acute and delayed symptoms (cisplatin > or = 50 mg/m2, carboplatin > or = 300 mg/m2, cyclophosphamide > or = 750 mg/m2, ifosfamide > or = 1.5 g/m2 on day 1). Group A: 1 x 5 mg tropisetron i.v. on day 1 + 2, then 10 mg p.o. (oral dose now recommended: 5 mg); group B: tropisetron as for A+dexamethasone, 20 mg i.v., on days 1 + 2, then 4 mg i.v./p.o.; group C: tropisetron as for A+metoclopramide, 20 mg i.v. +2 x 10 mg p.o. on day 1, then 3 x 10 mg p.o. Treatment was continued for at least 2 days after the end of chemotherapy. Tropisetron+dexamethasone was significantly superior to tropisetron alone both for acute (P = 0.0064) and delayed (P = 0.0053) emesis. Complete control of acute and delayed emesis (nausea) was achieved in 80% (75%) and 53% (46%) in group A, 97% (90%) and 80% (58%) in group B, and 86% (80%) and 49% (45%) in group C. Patients completely asymptomatic during the whole cycle accounted for 26% of those in group A, 49% in group B and 28% in group C. The most frequent adverse events were constipation (16.6%), headache (7.3%) and tiredness (7.3%). Once-daily tropisetron+dexamethasone over several days is well tolerated and is a simple means of achieving further significant improvement in the efficacy of tropisetron against acute and delayed symptoms.


Subject(s)
Antiemetics/administration & dosage , Antineoplastic Agents/adverse effects , Dexamethasone/administration & dosage , Indoles/administration & dosage , Metoclopramide/administration & dosage , Nausea/drug therapy , Vomiting/prevention & control , Acute Disease , Adult , Aged , Antineoplastic Agents/therapeutic use , Drug Administration Schedule , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Nausea/chemically induced , Quality of Life , Treatment Outcome , Tropisetron , Vomiting/chemically induced
16.
Clin Infect Dis ; 25(3): 706-12, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9314465

ABSTRACT

We offered standardized gynecologic examinations to consecutive women admitted to an AIDS-designated inpatient medical service; 65 (97%) of 67 women consented to the examination. The median CD4+ T lymphocyte count was 54/mm3. Only 9% of the women were admitted for primary gynecologic or genitourinary diagnoses; however, on evaluation, 83% of these women had gynecologic disease. The overall prevalences of vaginitis, cervical dysplasia, genital condylomata, genital herpes, and pelvic inflammatory disease were 51%, 45%, 23%, 20%, and 5%, respectively. Unexpected findings included adenovirus infection and foscarnet-associated genital ulcerations (two cases each). For predicting disease, gynecologic symptoms had a sensitivity of 76% and a positive predictive value of 95% but a negative predictive value of only 41%. Our results document the high prevalence of comorbid gynecologic disease among women infected with human immunodeficiency virus (HIV). Because of the inability to fully predict disease by symptom history, it is imperative that comprehensive gynecologic evaluation be offered routinely to all HIV-infected women hospitalized for acute medical illnesses.


Subject(s)
Genital Diseases, Female/complications , HIV Infections/complications , Adult , Condylomata Acuminata/complications , Female , Genital Diseases, Female/diagnosis , Herpes Genitalis/complications , Humans , Middle Aged , Pelvic Inflammatory Disease/complications , Predictive Value of Tests , Uterine Cervical Dysplasia/complications , Vaginitis/complications
17.
J Urol ; 158(3 Pt 1): 844-50, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9258096

ABSTRACT

PURPOSE: The cure rate of patients with germ cell cancer of the testis has considerably improved since the introduction of cisplatin based chemotherapy. Because these patients are in their reproductive years and because some of them will be infertile after treatment, the effects of cytotoxic treatment on gonadal function are investigated by hormonal evaluations. MATERIALS AND METHODS: In a transversal trial, luteinizing hormone, follicle-stimulating hormone and testosterone were determined radioimmunologically in serum samples of 232 patients with germ cell tumors after unilateral orchiectomy (patient age 18 to 64 years) up to 153 months after chemotherapy. Additionally, 51 of these patients were investigated in a longitudinal trial before and up to 5 years after chemotherapy. All patients received at least 2 courses of different cisplatin based chemotherapy regimens: cisplatin/vinblastine/bleomycin, cisplatin/vinblastine/bleomycin/ifosfamide, cisplatin/etoposide/bleomycin, cisplatin/vinblastine/bleomycin/ifosfamide/etoposide. Additionally, 11 patients with germ cell tumors (age 22 to 38 years, stage I) were investigated within the first year after orchiectomy and retroperitoneal lymphadenectomy but without chemotherapy. RESULTS: In the transversal trial, 24 of 73 patients investigated during the first year after chemotherapy showed elevated luteinizing hormone concentrations, 5 had subnormal serum testosterone and 65 had elevated serum follicle-stimulating hormone, reflecting spermatogenesis deficits. In 28 patients studied longer than 8 years after chemotherapy (median followup 8.5 years, range 8.0 to 12.6), luteinizing hormone increased after chemotherapy and 60 months after treatment, and follicle-stimulating hormone was elevated in 1 patient, follicle-stimulating hormone was increased in 18 and testosterone was subnormal in 1. Patients without chemotherapy treatment showed gonadotropin and testosterone within normal range and 3 patients had elevated serum follicle-stimulating hormone. In the longitudinal study, mean serum luteinizing hormone plus or minus standard deviation (3.45 +/- 0.05 IU/l.), follicle-stimulating hormone (7.79 +/- 0.13 IU/l.) and testosterone (18.6 +/- 0.17 nmol./l.) were within the normal range before chemotherapy; serum follicle-stimulating hormone was still significantly elevated (16.9 +/- 0.71 IU/l., 19 cases, p < 0.001). Mean luteinizing hormone and testosterone levels were within the normal range, but 60 months after therapy the testosterone-to-luteinizing hormone ratio was still lower than before treatment (p < 0.05). CONCLUSIONS: In patients with germ cell tumors, a compensated insufficiency of the function of the Leydig cells was still observed up to 60 months after chemotherapy. Of these patients 68% showed elevated follicle-stimulating hormone levels, which reflected a functional insufficiency of the Sertoli cells with impaired spermatogenesis. This study shows that impairment of germinative functions is more severe and protracted than the impairment of the endocrine functions.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Germ Cells/drug effects , Germinoma/drug therapy , Germinoma/physiopathology , Testicular Neoplasms/drug therapy , Testicular Neoplasms/physiopathology , Adolescent , Adult , Bleomycin/administration & dosage , Cisplatin/administration & dosage , Cross-Sectional Studies , Etoposide/administration & dosage , Follicle Stimulating Hormone/blood , Germ Cells/metabolism , Germ Cells/physiology , Humans , Ifosfamide/administration & dosage , Longitudinal Studies , Luteinizing Hormone/blood , Male , Middle Aged , Testosterone/blood , Vinblastine/administration & dosage
18.
Dtsch Med Wochenschr ; 122(22): 703-8, 1997 May 30.
Article in German | MEDLINE | ID: mdl-9213534

ABSTRACT

OBJECTIVE: To obtain population-related data, previously not available for Germany, regarding primary symptoms, diagnosis and treatment of patients with colorectal carcinoma. PATIENTS AND METHODS: During 1994, in the catchment area of Bonn (town of Bonn, districts of Euskirchen and Rhein-Sieg), there were 354 cases of newly diagnosed colorectal carcinoma. For all of them initial symptoms, primary diagnosis, cancer stage at time of diagnosis as well as surgical and conservative treatment were prospectively documented. By comparing entries from all relevant hospitals and doctors with those of the pathology institutes of the region, data of about 98% of all these patients were recorded. RESULTS: The average age of the patients was older (median of 69 for men, 72 for women) with more far metastases than in comparable groups reported by German university surgical departments. Only 4.6% of the group had occult blood in the stool as the only symptom. Most of the patients had local or regional metastases (T3-4: 63.9%; N1-3: 41%, respectively). Operations intended to be curative were possible in only 65.9% of the cohort. Adjuvant radiotherapy and/or chemotherapy was given to 11.7%, using current consensus recommendations.


Subject(s)
Adenocarcinoma/epidemiology , Carcinoma/epidemiology , Colorectal Neoplasms/epidemiology , Adenocarcinoma/pathology , Adenocarcinoma/secondary , Adenocarcinoma/therapy , Adult , Age Distribution , Aged , Aged, 80 and over , Carcinoma/pathology , Carcinoma/secondary , Carcinoma/therapy , Cohort Studies , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , Female , Germany/epidemiology , Humans , Male , Middle Aged , Neoplasm Staging , Prospective Studies
20.
Nephrol Dial Transplant ; 12(3): 593-5, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9075151

ABSTRACT

Immunosuppressed organ transplant recipients have a markedly increased risk of neoplasia. Among these malignancies acute myeloid leukaemia (AML) is rare. However, until now no case of successful chemotherapy has been reported. We present a 39-year-old male patient who developed AML (FAB M4 Eo) 4 years after renal transplantation and achieved a stable complete remission after induction therapy with standard dose cytarabine and daunorubicin. Remission duration is now 11 months. At present the transplant is functioning well after two additional courses of consolidation chemotherapy with high-dose cytarabine combined with mitoxantrone and idarubicine respectively. Cyclosporin A was given during all cycles of chemotherapy. We conclude that intensive chemotherapy in patients with AML following renal transplantation in good performance status is feasible.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Immunosuppression Therapy/adverse effects , Kidney Transplantation/adverse effects , Leukemia, Myeloid, Acute , Adult , Humans , Idarubicin/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/etiology , Male , Mitoxantrone/therapeutic use , Transplantation, Homologous
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