Biomedical subjects
Publications and source records attributed to H G Mergenthaler.
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The purpose of our study was (i) to evaluate the impact of all-trans retinoic acid (ATRA) given as adjunct to chemotherapy and (ii) to compare second consolidation vs maintenance therapy in elderly patients with acute myeloid leukemia (AML). A total of 242 patients aged >or=61 years (median, 66.6 years) with AML were randomly assigned to ATRA beginning on day +3 after the initiation of chemotherapy (ATRA-arm, n=122) or no ATRA (standard-arm, n=120) in combination with induction and first consolidation therapy. A total of 61 patients in complete remission (CR) were randomly assigned to second intense consolidation (n=31) or 1-year oral maintenance therapy (n=30). After induction therapy the intention-to-treat analysis revealed a significant difference in CR rates between the ATRA- and the standard-arm (52 vs 39%; P=0.05). Event-free (EFS) and overall survival (OS) were significantly better in the ATRA-compared to the standard-arm (P=0.03 and 0.01, respectively). OS after second randomization was significantly better for patients assigned to intensive consolidation therapy (P<0.001). The multivariate model for survival revealed lactate dehydrogenase, cytogenetic risk group, age, and first and second randomization as prognostic variables. In conclusion, the addition of ATRA to induction and consolidation therapy may improve CR rate, EFS and OS in elderly patients with AML.
The aims of this study were to establish the percentage of metastatic renal cell carcinoma (RCC) lesions detected by radioimmunoscintigraphy (RIS) with the chimeric monoclonal antibody 131I-cG250 versus positron emission tomography (PET) with 18F-labelled deoxyglucose ([18F]FDG), and to evaluate the use of these radionuclide imaging modalities compared with routinely used imaging techniques. Twenty patients with metastatic RCC disease were examined with [18F]FDG-PET and 131I-cG250 RIS within 1 week. Total body gamma camera images were obtained up to 120h after injection of 232MBq 131I-cG250. Total body PET scanning was performed 45-60 min after intravenous injection of 370MBq [18F]FDG. Nuclear medicine techniques were compared to routine imaging procedures. Routine imaging modalities revealed a total of 79 metastases. [18F]FDG-PET and 131I-cG250 RIS detected 33 previously unknown metastases, of which 32 were [18F]FDG positive and seven were 131I-cG250 positive. Of the 112 tumour lesions that were documented, [18F]FDG-PET detected 69% (77 out of 112), whereas 131I-cG250 RIS detected only 30% (34 out of 112). In conclusion, [18F]FDG-PET is superior to 131I-cG250 RIS in detecting metastases in patients with metastatic RCC, and therefore seems a promising tool for (re)staging patients with RCC. The usefulness of RIS with a diagnostic dose of 131I-cG250 seems to be restricted to selecting patients for radioimmunotherapy with 131I-cG250.
BACKGROUND: In Hodgkin disease (HD), accurate assessment of the extent of disease is essential because it provides the basis for different treatment strategies. In addition to conventional imaging methods (CIM), positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) may permit reliable differentiation between lymphoma and nonmalignant tissue and thus improve determination of the stage of the disease. The aim of the current study was to assess the clinical value of FDG-PET for primary staging, treatment monitoring, and assessment in a suspected case of recurrent HD. METHODS: Eighty-one patients with HD underwent 106 FDG-PET studies using a dedicated whole body PET ring scanner. In 25 patients PET was part of the primary staging, 63 PET studies were undertaken for treatment monitoring after the completion of treatment, and in 18 patients PET was performed in cases of suspected recurrence of HD. PET scans were compared with CIM and verified histologically and/or by follow-up evaluation (mean follow-up duration, 20.4 months). RESULTS: With regard to primary staging, in a patient to patient analysis, both PET scans and CIM were positive (i.e., showed pathologic foci indicative of HD) in 24 of 25 cases. In a staging-relevant lesion to lesion analysis, accuracy in the determination of the stage of disease was 96% for PET versus 56% for CIM. PET led to a lower stage classification in 28% and a higher stage classification in 12% of cases, compared with the stage assumed with CIM. With regard to treatment monitoring, PET showed an accuracy of 91% compared with 62% for CIM. The negative predictive value of PET was 96%. With regard to suspected recurrence, PET findings were true-positive in 10 of 12 PET scans and true-negative in 5 of 6 PET scans, resulting in accuracy of 83%, which compares favorably with the accuracy rate of 56% for CIM. CONCLUSIONS: It may be concluded that FDG-PET is capable of determining the stage of HD with great accuracy and is capable of correctly detecting manifestations of HD in treatment monitoring and cases of suspected recurrence, in which CIM occasionally result in equivocal findings. The results of the current study suggest that FDG-PET should become a routine tool in the staging/restaging of HD.
BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent inducer of physiological and neoplastic blood vessel growth. Moreover, in vitro studies have demonstrated that VEGF can be up-regulated by conditions associated with the generation of free radicals and reactive oxygen species. In a previous study we reported on strongly increased VEGF concentrations in the bronchoalveolar lavage fluid (BALF) of patients with lung cancer under therapy. In this study we aimed to reveal whether this increase was due to the therapy-associated intrapulmonary oxidative burden. PATIENTS AND METHODS: A total of 103 BALF samples from 94 patients with lung cancer (82 patients with non-small-cell lung cancer, 12 patients with small-cell lung cancer) were studied at different times before, during or after cancer treatment. VEGF levels in the lavage fluid and ratios of oxidised methionine in proteins of epithelial lining fluid (ELF) were determined. RESULTS: As reported previously, strongly increased VEGF levels in the ELF were observed in patients undergoing chemotherapy when radiotherapy had been administered before. Increased levels of oxidised methionine indicated that these patients suffered from severe pulmonary oxidative stress that was significantly less in patients undergoing only chemotherapy. Similarly, VEGF concentrations in the ELF were significantly elevated in cancer patients at the time of diagnosis, but the oxidised methionine levels did not reveal significant oxidant/antioxidant imbalances in these patients. CONCLUSION: Systemic chemotherapy is associated with oxidative stress in vivo, which is more pronounced if patients are additionally treated with radiation. VEGF levels in the ELF are increased by this condition as well as by the activity of the tumour itself.
BACKGROUND: This phase II study was initiated to determine the efficacy and safety of gemcitabine plus cisplatin in patients with pancreatic cancer. PATIENTS AND METHODS: Gemcitabine 1000 mg/m2 was given on days 1, 8, and 15 of a 28-day schedule, and cisplatin 50 mg/m2 on days 1 and 15 to chemonaive patients with locally advanced or metastatic pancreatic cancer. RESULTS: Of the 41 patients enrolled (median age 57, and 61% male), median Karnofsky performance status was 80%. Patients received a median of 4.2 cycles (range 1-11). In 35 evaluable patients, one complete response (CR) and three partial responses (PR) were observed, for an overall response rate of 11% (95% confidence interval (95% CI): 3.2% -26.7%). Stable disease (SD) > 3 months occurred in 20 (57%) patients; 6 survived > or = 1 year. Median time to progressive disease was 4.3 months (95% CI: 3.0-5.7 months). For all patients, median survival was 8.2 months (95% CI: 6.1-10.6 months) with a one-year survival rate of 27%. Therapy was well tolerated. Grade 3-4 neutropenia (no grade 3-4 infection), thrombocytopenia (no bleeding), nausea/vomiting, and alopecia were reported in 29%, 13%, and 2.6% of patients, respectively. CONCLUSIONS: The combination of gemcitabine and cisplatin is a moderately active treatment for patients with locally advanced and metastatic pancreatic cancer without compromising tolerability.
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BACKGROUND: Vascular endothelial growth factor (VEGF) plays a crucial role in physiological and neoplastic angiogenesis. Moreover, VEGF has been found to be upregulated by conditions associated with the generation of free radicals and reactive oxygen intermediates. In patients with cancer, studies to evaluate VEGF as a measure of tumour activity were carried out. We tested the hypothesis that VEGF is additionally affected by oxidative stress due to anticancer therapy. Moreover, the suitability of epidermal growth factor (EGF) to estimate tumour activity was studied. PATIENTS AND METHODS: 60 patients with non-small cell lung cancer (NSCLC) covering different therapy progress and modalities underwent bronchoalveolar lavage. VEGF-, EGF-, albumin- and total protein-concentrations in bronchoalveolar lavage fluid (BALF) and VEGF-levels in blood plasma were studied. RESULTS: BALF VEGF-levels were increased in patients with advanced NSCLC before and in anticancer therapy. In patients who had received radiotherapy to the lung prior to chemotherapy, VEGF concentrations were noticeably higher than under sole chemotherapy. Pulmonary endothelial hyperpermeability was found in patients with recently diagnosed tumours and patients undergoing anti-cancer therapy. Evaluation of EGF-levels in BALF revealed no significant influence of tumour activity or cancer therapy on this parameter. CONCLUSION: BALF-levels of VEGF are affected by tumour activity and oxidative stress due to anticancer therapy.
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Lung injury is one of the most frequent side effects in anticancer therapy. Especially simultaneous application of high doses of ionising radiation and radiosensitising cytotoxic drugs is considered to cause deleterious pneumonitis and pulmonary fibrosis. Growing evidence indicates that reactive oxygen species (ROS) play a key role in the development of these disorders. They are capable of causing cell component alterations and changing cellular protein expression. Observing these disease mechanisms reveals an impressive self-amplifying cascade of secondary ROS generation. Through intricate interactions between cells, cytokines and growth factors, fibroblasts are activated and thus pulmonary matrix content is massively increased. - As clinical appearance is uniform and unspecific, an early, reliable diagnosis of therapy-associated lung damage is not possible so far. However, improving this situation could enable us to take advantage of new multimodal therapeutic facilities. This review discusses mechanisms of ROS generation during radio-chemotherapy in the lung, antioxidant defense strategies and responses to oxidants, thereby assessing current diagnostic tools.
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Although eosinophilia has been reported as a side effect of purine analogues, there is no report on fludarabine-induced eosinophilia in chronic lymphocytic leukemia (CLL). During chemotherapy with fludarabine and cyclophosphamide, we observed two cases of significant eosinophilia. A 67-year-old patient with CLL developed bone marrow and peripheral blood eosinophilia up to 7.9x10(9)/l, the highest eosinophil count ever reported during treatment with a purine analogue. The eosinophilia persisted for 33 days. Another patient developed bone marrow eosinophilia without eosinophilia in the peripheral blood. These are the first documented cases of fludarabine-induced eosinophilia in CLL, and this side effect may conceivably be more common than previously recognized.
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Gemcitabine is an effective agent in the treatment of metastatic breast cancer. The phosphorylation of gemcitabine into the active gemcitabine triphosphate (dFdCTP) is catalyzed by deoxycytidine kinase. This enzyme is saturated at plasma concentrations achieved after an infusion over 30 min. Therefore accumulation of higher intracellular dFdCTP concentrations, which may result in an enhanced antineoplastic activity, cannot be achieved by higher dosage, but only by prolonged infusion time. The objectives of this phase I trial were to determine the dose-limiting toxicities (DLT) and the maximum tolerated dose (MTD) of gemcitabine given as a 6 h i.v. infusion. Patients with metastatic breast cancer were treated with gemcitabine as a 6 h infusion on days 1, 8 and 15 every 4 weeks. The starting dose was 200 mg/m2 with an interindividual escalation in 50 mg/m2 increments. Sixteen patients received 196 doses through three dose levels. All patients were assessable for toxicity, 13 assessable for response. The MTD was 250 mg/m2. DLT was observed at 300 mg/m2 consisting of a reversible elevation of transaminases WHO grade 3 in two patients and cutaneous toxicity grade 3 in one patient. Most common non-hematologic toxicities were mild to moderate and rapidly reversible elevation of liver enzymes in all patients, nausea and vomiting (four patients grade 2, five patients grade 3), and mild alopecia. Hematologic toxicity was mild with neutropenia WHO grade 3 and 4 in only one patient each, and no grade 3 thrombocytopenia. One patient achieved a complete remission and another patient a partial response, for an overall response rate of 15% (two of 13). In addition, seven patients (54%) had stable disease and four (31%) failed to respond to the treatment. We conclude gemcitabine 250 mg/m2 days 1, 8 and 15 every 4 weeks can be safely administered as 6 h infusion. Toxicity, especially myelosuppression, is surprisingly mild. Based on this result a phase II study with 250 mg/m2 administered over 6 h was initiated to determine the efficacy.
Gemcitabine is an active agent in the treatment of metastatic breast cancer. The phosphorylation of gemcitabine into the active gemcitabine triphosphate (dFdCTP) is catalyzed by deoxycytidine kinase. This enzyme is saturated at plasma concentrations achieved after an infusion over 30 min. Therefore accumulation of higher intracellular dFdCTP concentrations, which may result in an enhanced antineoplastic activity, cannot be achieved by higher dosage, but only by prolonged infusion time. In a previous phase I trial the maximum tolerated dose of gemcitabine given as a 6 h i.v. infusion was 250 mg/m2. The objective of this phase II trial was to determine the efficacy and safety of gemcitabine as prolonged infusion in patients with metastatic breast cancer. Twenty patients [median age 50.4 years, range 35-63 years; performance status EORTC 0 (17 patients), 1 (two patients), 2 (one patient)] with metastatic breast cancer were treated with 250 mg/m2 gemcitabine as infusion over 6 h on days 1, 8 and 15 q3 weeks for up to six courses (median 3.9 courses). Treatment was first line for four patients, second line for five patients and third line or higher for 11 patients. Metastatic sites were liver in 14 patients, bone in 12 patients, lung in eight patients and lymph nodes in nine patients. Nine patients presented two metastatic sites, three patients three and five patients four. All patients were evaluable for response and toxicity. One patient (5%) achieved a complete remission (CR) and four patients (20%) a partial remission (PR) (one patient with CR of visceral metastases but stable bone metastases), for an overall response rate of 25% (five of 20). In addition, six patients (30%) had stable disease and nine (45%) failed to respond to the treatment. Time to progression ranged from 2 to 23 months with a median of 6.3 months. Hematologic toxicity was mild with leukopenia grade 3 in only three patients (15%) and no grade 3 thrombocytopenia. Moderate elevations of liver enzymes (three patients grade 3), nausea and vomiting (two patients grade 2), and mild alopecia were observed, but only one patient had to be withdrawn due to toxicity. In conclusion gemcitabine as prolonged infusion is an effective treatment in metastatic breast cancer. Toxicity, especially myelosuppression, is surprisingly mild. Therefore, gemcitabine seems to be ideal for combination therapies.
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Explore the source record for details and available documents.