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J Beyer

Publications and source records attributed to J Beyer.

At least 37 records · Page 2Linked to original sources

Analysis of salvage treatments for germ cell cancer patients who have relapsed after primary high-dose chemotherapy plus autologous stem cell support.

The aim of this study was to identify treatment strategies and therapeutic or clinical factors that predict for response to salvage therapy and survival in patients with metastatic 'Indiana advanced' or International Germ-Cell Cancer Collaborative Group (IGCCCG) poor prognosis' germ cell cancer (GCT) failing first-line sequential high-dose chemotherapy plus autologous stem cell support (HD-CT). A total of 58 'poor prognosis' patients who had relapsed after HD-CT were identified within two large prospective German first-line HD-CT trials (n=286) performed between March 1993 and March 2001. Salvage treatment consisted of the following: cisplatin-based conventional dose CTx+/-resection (19/58; 33%), non-cisplatin based CTx (16/58; 28%) or salvage HD-CT (14/58; 24%)+/-resection; resection (n=3) and/or radiation (n=5) only: 7 patients (12%); no specific therapy: 2 patients. 21 (38%) patients responded favourably (Complete Response (CR)/Partial Response (PR) marker-negative) to salvage therapy. The use of salvage HD-CT (2-year survival 48%; P=0.03, the complete resection of residual masses (2-year survival 42%; P=0.015) as well as a favourable response to salvage therapy (2-year survival: 31%, P=0.014) were the only variables on univariate analysis associated with an improved survival. The estimated 2-year overall survival rate is 32% (95% Confidence Interval CI: 29-45%). Approximately 30% of patients relapsing after first-line HD-CT will survive>2 years, particularly those patients who can be treated with a second HD-CT +and/or surgical resection. If feasible, complete surgical resection of residual tumours appears to be the most efficient treatment.

Adolescent↗

Current aspects of high-dose chemotherapy in germ-cell tumors.

The optimal treatment in patients with 'poor prognosis' germ-cell tumors (GCT) according to the 'International Germ Cell Cancer Collaborative Group' (IGCCCG)--classification and in patients with refractory or relapsed disease after cisplatin-based chemotherapy remains controversial. It is well known that the majority of these patients will suffer systemic relapses after primary or salvage treatment and most of them will ultimately die of their disease. Therefore, the optimizing of the standard treatment is clearly desirable. The question of using conventional-dose or high-dose chemotherapy (HDCT) in this high-risk patients is under discussion. However, HDCT as primary treatment in 'poor prognosis' patients and as first- or subsequent salvage therapy in patients with relapsed or refractory GCT remains to be a relevant curative option. Prognostic factors have recently been recognized to aid in this decision.

Antineoplastic Agents↗

Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia: disease status by marrow blasts is the strongest prognostic factor.

We analyzed predictive factors for the outcome of 113 acute myeloid leukemia patients receiving reduced-intensity conditioning prior to allogeneic hematopoietic stem cell transplantation (HSCT). Patients were ineligible for conventional-intensity HSCT. Conditioning consisted of fludarabine and 50% of the conventional dose of busulfan (n=93) or total body irradiation (n=20). The source of stem cells was blood in 102 patients, marrow in 10, and both in one. In total, 50 (44.2%) donors were HLA-matched siblings, 50 (44.2%) unrelated fully matched and 13 (11.5%) partially mismatched family (n=1) or unrelated (n=12) donors. In all, 107 (94.6%) patients showed neutrophil and platelet engraftment after a median time of 13.5 and 13 days. The probabilities of event-free survival (EFS) (median follow-up: 12 months) were 49% for patients with less than 5% blasts in the marrow, 24% for patients with 5-20% blasts (P=0.002) and 14% with >20% blasts (P<or=0.001). Death occurred because of relapse in 29 patients (25.6%), infection in 12 patients (10.6%), acute graft-versus-host disease in eight patients (7.0%) and organ toxicity in nine patients (7.9%). In multivariate analysis, higher number of blasts in the marrow, alternative donors and low Karnofsky performance score were independent adverse prognostic factors for EFS.

Adolescent↗

Pilot study with technosphere/PTH(1-34)--a new approach for effective pulmonary delivery of parathyroid hormone (1-34).

Sequential subcutaneous PTH injection therapy (repeated 14 days of PTH administration and a subsequent treatment pause for a few weeks) is known to increase bone mineral density in patients with osteopenic disorders. Alternative methods of drug delivery may be beneficial in increasing compliance. A pilot study was performed in 10 healthy volunteers (4 female/6-male, age: 25.6 +/- 3.5 years, BMI: 22.3 +/- 2.4 kg/m 2, mean +/- SD) to assess the pharmacokinetic profiles of 1600 IU of PTH(1 - 34) using the pulmonary Technosphere drug delivery system in comparison to a subcutaneous injection of 400 IU. The treatments were administered in the morning after an overnight fast and blood samples for measurement of PTH(1 - 34), PTH(1 - 84), and calcium and calcitonin were taken over a period of 6 hours. Both injection and pulmonary application of PTH(1 - 34) were well tolerated. After pulmonary administration of Technosphere/PTH(1 - 34), PTH(1 - 34) appeared in the serum with a faster concentration increase (T max: pulmonary 10 +/- 5 min vs. subcutaneous 28 +/- 8 min, p < 0.001) and with higher maximal concentrations (C max : pulmonary 309 +/- 215 pmol/l vs. subcutaneous 102 +/- 45 pmol/l, p < 0.05) as compared to the subcutaneous injection. The relative bioavailability of pulmonary Technosphere/PTH(1 - 34) was calculated to be 48 %. No differences were seen between pulmonary and subcutaneous application with regard to the PTH(1 - 84), calcitonin and calcium concentrations. In conclusion, pulmonary application of Technosphere/PTH(1 - 34) appears to be an effective and thus attractive candidate for PTH substitution therapy in osteoporosis and other conditions leading to a decrease in bone mineral density.

Adult↗

Biocompatibility of alginates for grafting: impact of alginate molecular weight.

Optimising microencapsulation technology towards the effective clinical transplantation has created the need for highly biocompatible alginates. Therefore, in this study the biocompatibility of different beads prepared from alginates with varying average molecular weight was examined. In some experiments the beads were covered with a multilayer membrane surrounded by an alginate layer. First of all, we found that beads made of a lower weight average alginate elicted a much stronger fibrotic response compared to beads made of a higher weight average alginate (LV-alginate > MV-alginate). The results were confirmed by the observation that the extent of tissue fibrosis was significantly increased in multilayer capsules made of an alginate with a lower weight average (core and surface LV-alginate, Mw 0.7-1 * 10(6) g/mol, viscosity of a 0.1% solution 1-2.5 mPa s(-1)) compared to multilayer capsules made of an alginate with a higher weight average (core and surface MV-alginate; Mw 1.2-1.3 * 10(6) g/mol, viscosity of a 0.1% solution 5-7 mPa s(-1)). It should be stressed, that the pro-fibrotic effect of the LV-alginate alginate in the core was only partially reversed by a MV-alginate on the surface of the multilayer capsules. On the basis of the raised data, it can be assumed that the molecular weight average of the alginates have an decisive effect on the biocompatibility. Therefore, it seems to be recommendable to reduce the low molecular weight fractions of the alginate during the purification process to improve the biocompatibility.

Alginates↗

Marked increase of the growth factors pleiotrophin and fibroblast growth factor-2 in serum of testicular cancer patients.

BACKGROUND: Malignant tumors of the testis are among the most common cancers in men between the ages of 15 and 30 years. The sensitivity of detection of known tumor markers depends upon the tumor histology and stage. In other cancers, increased serum concentrations of various angiogenic growth factors have been described as potential markers for tumor progression and metastasis. One main histological feature of testicular cancer is profound angiogenesis. DESIGN: In this study, we investigated by sensitive enzyme-linked immunosorbent assays (ELISAs) the levels of various growth and angiogenesis factors in the serum of testicular cancer patients as compared with normal control subjects. For the most profoundly increased growth factors, pleiotrophin (PTN) and fibroblast growth factor-2 (FGF-2), we furthermore analyzed tumor lysates by northern blotting, RT-PCR and ELISA. RESULTS: We demonstrate a marked elevation of average serum levels of PTN ( approximately 20-fold) and of FGF-2 ( approximately 7-fold) in patients and expression of both growth factors in tumor biopsies. To a lesser extent, vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) serum levels were increased, whereas FGF-4 and transforming growth factor-beta levels were similar to those in normal control subjects. Elevation of PTN, FGF-2, EGF and VEGF was detected in seminomatous as well as non-seminatous tumors, and even in early stages. CONCLUSIONS: PTN and FGF-2 may represent promising new diagnostic markers for testicular cancer with high sensitivity even in early-stage testicular cancer. Further studies are warranted to extend our analyses.

Adult↗

Influence of amifostine on reconstitution of lymphocyte subpopulations after conventional- and high-dose chemotherapy in patients with germ cell tumor.

We assessed the influence of amifostine on immune reconstitution after conventional-dose paclitaxel, ifosfamide, cisplatin and high-dose carboplatin, etoposide and thiotepa followed by autologous peripheral blood progenitor cell (PBPC) rescue in patients with germ cell tumor (GCT). A total of 40 patients were treated with one cycle of paclitaxel and ifosfamide (TI) followed by granulocyte-colony stimulating factor (G-CSF) to mobilize PBPC, three cycles of paclitaxel, ifosfamide and cisplatin (TIP) and one course of high-dose carboplatin, etoposide and thiotepa (CET) plus PBPC rescue. Patients were randomized to receive an absolute dose of 500 mg amifostine (group A, n=20) on each day of chemotherapy or no amifostine (group B, n=20). Prior to each cycle of chemotherapy, after hematologic engraftment from CET, 6 weeks and 3 months after transplantation the subpopulations of lymphocytes were phenotyped. Between the two study groups no statistically significant differences were observed concerning reconstitution of lymphocyte subpopulations. Throughout treatment with TIP or CET lymphocyte counts and their subpopulations remained low without severe clinical complications. Delayed reconstitution of the CD4(+) cell compartment after PBPC rescue was observed in both study groups, but did not result in any severe or atypical infections. Treatment with amifostine administered at this dose did not significantly influence the reconstitution of lymphocyte subpopulations. Low numbers of lymphocytes during chemotherapy and delayed reconstitution of CD4(+) cells and other lymphocyte subpopulations after PBPC rescue had no clinical relevance for patients with GCT.

Adult↗

The collagen Ia1 SP1 polymorphism is associated with differences in ultrasound transmission velocity in the calcaneus in postmenopausal women.

Bone mineral density (BMD) and fracture risk are under genetic control. An association of a G to T polymorphism in the Sp1 binding site of the collagen Ia1 (COLIa1) gene with the risk for fractures has been previously reported. This association is only partly explained by differences in BMD. Thus, we analyzed the relationship between the COLIa1 Sp1 polymorphism and ultrasound (US) transmission velocity (speed of sound; SOS) in bone. In a population-based sample of 740 women (aged 55-80 years) we determined COLIa1 genotype and US parameters in the calcaneus. SOS in the "GG" genotype group was 1522 +/- 31 m/sec, in the "GT" group, 1519 +/- 30 m/sec, and in the "TT" group 1508 +/- 30 m/sec (P = 0.01). While the difference between the GG and TT genotype groups corresponds to 0.5 SD or 1%, we observed an allele-dose-effect of 4.3 m/sec decrease in SOS per each copy of the "T" allele (P = 0.01). The differences remained significant after adjustment for BMD measured at the femoral neck. When we analysed 45 incident nonvertebral fractures in this group of women, we found the risk for fracture by COLIA1 Sp1 genotype to be partly explained by SOS differences as well as by BMD differences. Linear regression analysis showed a progressive negative slope of the regression line of SOS over age from "GG" over "GT" to "TT" genotype. These data indicate that the collagen Ia1 Sp1 polymorphism is associated with the modulus of elasticity of bone as determined in vivo by acoustical measurement. The relationship is independent of BMD and increases with age, contributing to an explanation of the increased fracture risk observed for this polymorphism.

Aged↗

[Cushing's syndrome caused by paraneoplastic ACTH secretion 11 years after occurence of a medullary thyroid carcinoma].

HISTORY AND ADMISSION FINDINGS: A 47-year-old man, with known and treated hypertension for 2 years, was admitted because of recent marked weight gain. Eleven years before a medullary thyroid carcinoma had necessitated removal of his thyroid and parathyroids. He was not receiving levothyroxine, calcium and vitamin D. Physical examination revealed florid Cushing's syndrome with a "buffalo hump", plethora, truncal obesity and red striae. Both his mother and a maternal male cousin were reported to have had a medullary thyroid carcinoma. INVESTIGATIONS: Plasma ACTH was 80 pg/ml (normal 10-70 pg/ml), urinary cortisol 764 microgram/24 h (normal 20-100 microgram/24 h). ACTH rose to 93.1 pg/ml after dexamethasone, with little suppression of serum cortisol (reduced from 34.4 to 22.1 microgram/dl; normal 7-25 microgram/dl. Magnetic resonance imaging did not detected an abnormal hypophysis. Petrosal sinus catheterization revealed hypophyseal suppression of ACTH, without evidence of focal peripheral ACTH production. Calcitonin was 24 000 pg/ml (normal < 8.8 pg/ml). Computed tomography showed multiple round lesions in the liver (histology: metastasis of a C-cell carcinoma). Genetic test showed a multiple endocrine neoplasm type IIa. DIAGNOSIS, TREATMENT AND COURSE: The findings indicated Cushing's syndrome, most likely due to paraneoplastic ACTH secretion from a metastasis of the C-cell carcinoma. In the absence of a site of paraneoplastic ACTH secretion, bilateral adrenalectomy was performed. The plethora and striae regressed postoperatively and it was possible to reduce markedly the antihypertensive medication. CONCLUSION: An ectopic site of ACTH should be included in the differential diagnosis of Cushing's syndrome. This is the first reported case of a medullary thyroid carcinoma and ectopic ACTH production in which the paraneoplastic ACTH secretion had been delayed for 11 years.

Adrenalectomy↗

Activity of oxaliplatin in patients with relapsed or cisplatin-refractory germ cell cancer: a study of the German Testicular Cancer Study Group.

PURPOSE: To investigate the efficacy and toxicity of oxaliplatin, a diaminocyclohaxane platinum derivative with incomplete cross-resistance to cisplatin in patients with relapsed or cisplatin-refractory germ cell cancer. PATIENTS AND METHODS: Thirty-two patients with nonseminomatous cisplatin-refractory germ cell cancer or relapsed disease after high-dose chemotherapy (HDCT) plus autologous stem-cell support were treated with single-agent oxaliplatin 60 mg/m(2) on days 1, 8, and 15 repeated every 4 weeks (group 1; n = 16) or oxaliplatin 130 mg/m(2) given on days 1 and 15 of a 4-week cycle (group 2; n = 16). Patients were pretreated with a median of seven (range, three to 13) cisplatin-containing treatment cycles; 78% had received carboplatin/etoposide-based HDCT before oxaliplatin therapy. Twenty-seven patients (84%) were considered refractory (n = 20; 63%) or absolutely refractory (n = 7; 22%) to cisplatin therapy. RESULTS: Overall, four patients achieved a partial remission (13%; 95% confidence interval, 1% to 24%). Two additional patients achieved disease stabilization. All responses were observed in cisplatin-refractory patients, including three who had not responded to previous HDCT. Patients received a median two cycles of oxaliplatin with a median cumulative dose of 350 mg/m(2). Hematologic toxicity was generally mild, with five patients developing grade 3/4 thrombocytopenia. Nonhematologic side effects consisted mainly of nausea/vomiting. One patient developed grade 3 neurotoxicity. CONCLUSION: Considering the particularly unfavorable prognostic characteristics of this patient population compared with patients from previous trials for new drugs in germ cell cancer, eg, paclitaxel and gemcitabine, a 13% overall response rate and a 19% response rate in the group treated with oxaliplatin 130 mg/m(2) seems to be of interest. Oxaliplatin may be a palliative treatment option for this patient population, and evaluation in combination regimens is warranted.

Adult↗

The influence of local capsaicin treatment on small nerve fibre function and neurovascular control in symptomatic diabetic neuropathy.

Topical treatment with capsaicin cream has been shown to be successful in the treatment of different symptomatic nerve disorders like diabetic neuropathy. Conflicting data exist on the effect of capsaicin on nerve function and neurovascular control especially in patients with diabetic neuropathy. The aim of this pilot study was to investigate the impact of topical capsaicin application on small nerve fibre function and neurovascular control. Capsaicin cream was applied to the feet of 13 patients with symptomatic diabetic neuropathy over a period of 8 weeks. Before and during the treatment period, we investigated the total symptoms score, the vibration, thermal (heat and cold) and pain perception thresholds, and the neurovascular responses to heat and acetylcholine stimuli. In addition, the serum plasma levels of substance P, a neurotransmitter of nociceptor C-fibres, were measured. A significant improvement in total symptoms score was observed during topical capsaicin treatment (18.3+/-3.2 vs. 14.3+/-3.3; p<0.05). An improvement in the heat perception threshold was also found (12.7+/-0.4 degrees C vs. 11.4+/-0.7 degrees C: p<0.05), while other sensory nerve fibre functions remained unchanged. No significant change in neurovascular control was observed, neither after mild thermal injury nor after stimulation with acetylcholine. Serum substance P levels increased after initiation of topical capsaicin treatment (72.9+/-5.8 pg/ml vs. 81.7+/-5.0 pg/ml; p<0.05), but returned to baseline levels during further treatment (77.4+/-8.3 pg/ml: n.s.). In conclusion, topical treatment with capsaicin cream over a period of 8 weeks in patients with symptomatic diabetic neuropathy is effective without adverse effects on nerve fibre function or neurovascular control.

Administration, Topical↗

High-dose chemotherapy as salvage treatment for seminoma.

Between October 1989 and February 1997, 13 patients with refractory or relapsed seminomas were treated with high-dose chemotherapy (HDCT) as part of consecutive phase I/II studies. Six patients had failed prior cisplatin-based first-line treatments and seven patients had also failed cisplatin-based salvage treatments. After HDCT 4/12 (33%) patients became disease-free, 4/12 (33%) patients achieved partial remissions and 4/12 (33%) patients suffered progressive disease despite HDCT. One patient developed multiorgan failure and died. With a median follow-up of 4.5 years (range 3.4 to 8 years) five patients (38%) are alive and eight patients (62%) have died. Patients with non-pulmonary visceral metastases, with short relapse-free intervals and with cisplatin-refractory tumors were more likely to fail. HDCT can be curative in seminoma patients even if offered as second salvage treatment.

Adult↗

Cattle infected with bovine leukaemia virus may not only develop persistent B-cell lymphocytosis but also persistent B-cell lymphopenia.

We investigated the distribution of B and T cells in the peripheral blood of haematologically inconspicuous (non-persistent lymphocytotic, PL-) cattle infected with the bovine leukaemia virus (BLV). Flow cytometric data were obtained from six PL- cattle and compared with six age-matched animals with persistent lymphocytosis (PL+) and five non-infected healthy controls (BLV-). In the PL- group, the percentage and number of surface immunoglobulin-positive (sIg+) B cells were significantly reduced. Whereas in BLV-cattle, about 40% of the peripheral blood lymphocytes (PBL) were sIg + and 24% were sIgM + B cells. In the PL- group, less than 20% of the PBL were sIg+ and sIgM+ B cells. Only 5% of the PBL co-expressed sIgM+ and CD5+ versus 16% in BLV-. This decrease was persistent over 3 years and predominantly affected: (i) B cells that did not express sIgM; (ii) sIgM + B cells co-expressing CD5 and CD11b; and (iii) equally both lambda- and K-type light chain B-cell subpopulations. In contrast, the number of all circulating lymphocytes, CD5- and CD11b- sIgM+ B cells and CD2+ T cells did not differ. In PL+ animals, about 75% of the PBL were sIgM+ CD5+ B cells. These cells were of polyclonal origin, as light chains of the lambda- and K-type were expressed in a ratio of 4:1 (57.7% of PBL lambda+, 14% kappa+) as in BLV- animals (33.6% of PBL lambda+, 8.7% kappa+). In PL+ cattle the absolute number of B-cells and, therefore, their relative percentage is significantly increased. For this reason, even in case of absolutely increased T-cell numbers, the relative percentage of T-cells could be lower than in normal controls. The cause for the observed B cell decrease in PL- cattle is unknown, but it can be assumed that cytotoxic T cells are involved in this B-cell lymphopenia.

Animals↗

Abnormal pentagastrin response in a patient with pseudohypoparathyroidism.

The case of a 25 year old female patient with pseudohypoparathyroidism type I (PHP) and hypercalcitoninaemia is reported. She was referred to our clinic because of recurrent hypocalcaemia associated with paraesthesias and muscle cramps. She had no signs of Albright hereditary osteodystrophy (AHO), a normal mental status and no family history of hypocalcaemia or any other endocrine disease. Considering the laboratory results with hypocalcaemia, hyperphosphataemia, normal vitamin D and normal creatinine with an extraordinary elevated PTH we diagnosed pseudohypoparathyroidism type I. She had delayed pubertal development with menarche in the age of 20 and hypothyroidism with an atrophic thyroid since she was 22 years old. Calcitonin (CT) was increased and the performed pentagastrin test showed an excessive CT-response with a peak of 725 pg/ml after 2 min. Up to now there are only three reports of patients with PHP and hypercalcitoninaemia. An abnormal pentagastrin response is known to be a specific marker for medullary thyroid carcinoma, but there were no signs of any malignant disease, even after one year of follow-up. The most reasonable cause for the pathological pentagastrin response might be chronic hypocalcaemia. When interpreting a pathological pentagastrin test in a patient with PHP the specifity of the test might be diminished and a careful observational strategy might be appropriate.

Adult↗

Determination of the modulus of elasticity of bone material by an acoustical approach at the forearm distinguishes women with and without vertebral fractures independent of bone mineral density.

The modulus of elasticity is a parameter characterizing fracture stability of bone independent of bone mineral density. Measurement of acoustical properties of the forearm by determination of the resonant frequency of the ulna in longitudinal direction as a function of sound transmission velocity after adjustment of the measuring result by ulna length yields information about the modulus of elasticity. It was the aim of this study to investigate whether this parameter may distinguish between subjects with and without vertebral fractures independent of bone mineral density. Fifty females (61.1 +/- 9.1 years) were enrolled into the study, 25 with, and 25 age-matched without prevalent osteoporotic vertebral fracture(s). Especially low bone mineral density was not considered an exclusion criteria for enrollment into the control group. Resonant frequency of the ulna multiplied by ulna length was significantly lower in the group with prevalent fractures (53.6 +/- 6.8 m/s versus 56.8 +/- 5.2 m/s) after adjustment for age and after additional adjustment for forearm bone mineral density. Linear regression analysis showed complete independence of the acoustical parameter from bone mineral density. This study demonstrates that the modulus of elasticity of bone material is an independent risk factor for osteoporotic fractures. Acoustical measurement at the forearm by analyzing the resonant frequency of the ulna and correcting it by ulna length as geometrical parameter is capable of determining the modulus of elasticity in vivo.

Acoustics↗

Differences in pharmacokinetics and pharmacodynamics of insulin lispro and aspart in healthy volunteers.

Pharmacokinetic and pharmacodynamic profiles of the rapid-acting insulin analogues lispro and aspart were compared in a randomized, double-blind crossover study of 20 fasting healthy men following a single subcutaneous injection. Either insulin lispro or aspart, 0.05 U/kg-body-weight, was injected subcutaneously and followed by determination of 5-h profiles of plasma glucose, serum C-peptide and insulin concentrations. Lowest glucose concentrations were observed after 50 min in the aspart group (3.2 +/- 0.1 mmol/l versus lispro 3.5 +/- 0.1 mmol/l; p = 0.026) and after 60 min in the lispro group (3.4 +/- 0.1 mmol/l). For blood glucose t min was 59.3 +/- 3.4 min in the aspart and 63.5 +/- 5.3 min in the lispro group (ns). After 40 min a lower C-peptide was determined for aspart (225 +/- 21 pmol/l versus lispro 309 +/- 33 pmol/l; p = 0.031), whereas minimal C-peptide concentrations were reached in both groups after 105 min (lispro 117 +/- 21 pmol/l versus aspart 105 +/- 18 pmol/l). The maximal concentration of insulin was detected in both groups after 40 min (lispro 20.8 +/- 1.1 mU/l versus aspart 24.6 +/- 1.3 mU/l; p = 0.032). For insulin t max was 33.0 +/- 2.6 min in the aspart versus 33.3 +/- 2.6 min in the lispro group (ns). The present results indicate a more rapid absorption of insulin aspart in comparison to insulin lispro. Higher insulin concentrations after subcutaneus injection may be advantageous in meal-related treatment of diabetes.

Adult↗

High-dose versus conventional-dose chemotherapy as first-salvage treatment in patients with non-seminomatous germ-cell tumors: a matched-pair analysis.

BACKGROUND: The purpose of this study was to compare high-dose chemotherapy (HDCT) with conventional-dose chemotherapy (CDCT) as first-salvage treatment in patients with relapsed or refractory non-seminomatous germ-cell tumors (NSGCT). PATIENTS AND METHODS: One hundred and ninety-three patients with relapsed or refractory NSGCT, between 1981 and 1995, were identified from two large databases. In 74 of these, intensification of first-salvage treatment by HDCT was planned. Patients were matched based on primary tumor location, response to first-line treatment, duration of this response and serum levels of the tumor markers, human chorionic gonadotrophin (HCG) and alpha-fetoprotein (AFP). Multivariate analyses were performed using event-free survival and overall survival as primary endpoints. RESULTS: Full matches on all five factors were found for 38 pairs of patients; for a further 17 pairs, matches on at least four factors could be identified. Hazard ratios in favor of HDCT were obtained between 0.72 and 0.84 [confidence interval (CI) 0.59-1.01] for event-free survival and between 0.77 and 0.83 (CI 0.60-0.99) for overall survival, depending on the type of analysis. CONCLUSIONS: The current analysis suggests a benefit from HDCT, with an estimated absolute improvement in event-free survival of between 6 and 12% and in overall survival of between 9 and 11% at 2 years. This benefit is lower than expected from previous phase I/II studies.

Antineoplastic Combined Chemotherapy Protocols↗