Evaluation of psychosocial distress in patients treated in a community-based oncology group practice in Germany.

BACKGROUND: Systematic evaluation of psychosocial distress in oncology outpatients is an important issue. We assessed feasibility and benefit of standardized routine screening using the Distress Thermometer (DT) and Problem List (PL) in all patients of our community-based hematooncology group practice. PATIENTS AND METHODS: One thousand four hundred forty-six patients were screened between July 2008 and September 2008. Five hundred randomly selected patients were sent a feedback form. RESULTS: The average distress level was 4.7, with 37% indicating a distress level >5. Patients with nonmalignant diseases (81% autoimmune diseases or hereditary hemochromatosis) showed the highest distress level of 5.2. Most distressed were patients who just learned about relapse or metastases (6.4), patients receiving best supportive care (5.4) and patients receiving adjuvant antihormonal therapy (5.4). Ninety-seven percent of patients appreciated to speak to their doctor about their distress. Fifty-six percent felt better than usual after this consultation. CONCLUSION: DT and PL are feasible instruments to measure distress in hematooncology outpatients receiving routine care. DT and PL are able to improve doctor-patient communication and thus should be implemented in routine patient care. The study shows that distress is distributed differently between individuals, disease groups and treatment phases.

The impact of new treatment options for advanced colorectal cancer on routine care: results of a retrospective analysis of 206 consecutive patients treated in a community-based oncology group practice in Germany.

Due to necessary selection criteria, the results obtained in clinical trials may not reflect the actual impact of current treatment options for unselected general populations. We analysed the treatment modalities and the outcome in 206 consecutive patients with advanced colorectal cancer who started treatment between 1/1999 and 11/2004. The median age of this cohort was 66 years (range 30-87) and 39 patients (19%) were ≥ 75 years old. First-line treatment consisted of low-dose bolus 5-fluorouracil and folinic acid regimens in 68 patients (33%), weekly 24-h 5-fluorouracil infusion and folinic acid in 36 patients (17%), weekly 24-h 5-fluorouracil infusion plus oxaliplatin or irinotecan in 60 patients (29%), capecitabine regimens in 22 patients (11%), monotherapy with oxaliplatin or irinotecan in six patients (3%) and other regimens in 14 patients (7%). A total of 166 patients (81%) received a second-line treatment and third-line chemotherapy was given to 122/206 patients (59%). With a minimum follow-up of 18 months, the median survival of the cohort is 21 months (range 1-85) and 17 months (range 3-57) for patients ≥ 75 years. We conclude that the increased survival seen in prospective studies can be transferred to routine care for unselected patients with advanced colorectal cancer.

Follow-up Reality for Breast Cancer Patients - Standardised Survey of Patients and Physicians and Analysis of Treatment Data.

Introduction: Currently, about 360 000 breast cancer patients who could, after completion of their primary therapy, take advantage of follow-up options are living in Germany. Up to now very little is known about the extent to which the available options are used and as to how the follow-up reality is experienced and evaluated. Thus, an explorative examination among the patients and their physicians was undertaken. Patients and Methods: All patients who underwent surgery in a certified breast centre between 2007 and 2013 received a standardised questionnaire; at the same time the physicians responsible for the follow-up were invited to answer a standardised questionnaire. Results: 920 patients (response rate: 61 %) with a median age of 65 years (32-95) could be analysed. 99 % of the participants stated that they regularly attended follow-ups. The personal contact with the physician (mean value: 4.4) and the reassurance that the cancer disease had not recurred (mean value: 4.5) were described on a scale of 0 to 5 to be two of the most important factors of the follow-up. Deficits were expressed with regard to psychosocial care (70 %) and the perception and treatment of physical complaints (55 %). In addition, 105 physicians returned completed questionnaires (response rate: 12 %). For asymptomatic patients the physicians performed the following examinations most frequently: anamnesis (92 %), physical examination (87 %) as well as laboratory tests (63 %) and tumour marker determinations (40 %). Conclusion: On the whole it became clear that the vast majority of the patients took advantage of the follow-up options. From the patient's perspective the importance of the follow-up lies in contact to the physician and the comforting assurance that the breast cancer has not relapsed. Deficits are seen in the psychosocial care and the perception and treatment of physical impairments. Not recommended examinations were employed by a significant proportion of the surveyed physicians.

Altered expression of the retinoblastoma gene product in human high grade non-Hodgkin's lymphomas.

The retinoblastoma gene (RB) is a growth suppressor gene on the human chromosome 13q14. It encodes a 105 kDa phosphoprotein (p105), with DNA-binding capacity. P105 is thought to be involved in cell cycle control. Inactivation of RB is responsible for the development of retinoblastomas and occurs frequently in osteosarcomas and small cell lung cancer. In this study we looked at the RB-structure and expression in cell lines and primary lymphoma samples from patients with high grade non-Hodgkin's lymphoma (NHL). Forty five primary high grade NHL, the B-lymphoblastoid cell line IM-9 and the NHL cell line WSU-NHL were studied for RB structure by Southern blotting and for RB-expression by Northern blotting, Western blotting and immunocytochemistry. In all experiments freshly cryopreserved material was used. Southern and Northern experiments were performed with the 0.9 kb and 3.8 kb RB-cDNA probe. For the detection of p105 two different anti-p105-monoclonal antibodies were used in immunocytochemistry and Western blotting experiments. No RB mRNA and no p105 could be found in IM-9 cells. Twenty six high grade NHL samples (58%) showed no p105 expression. In the subgroup of centroblastic lymphomas 16 out of 21 and in Burkitt's lymphomas five out of eight showed no p105-expression. P105 expression is absent in 58% of high grade NHL, particularly in centroblastic and Burkitt's lymphomas, suggesting that inactivation of RB may play a crucial role in the pathogenesis of high grade NHL.

[Lymphomas: new therapeutic options]. / Lymphomverdacht. Wie gehen Sie vor, welche Chancen hat ihr Patient?

Malignant lymphomas are differentiated clinically, morphologically and molecular-biologically, into aggressive (formerly high-grade malignant) and indolent (formerly low-grade malignant) lymphomas. In the meantime, virtually all patients can be diagnosed and treated on an ambulatory basis. The introduction of the monoclonal antibody rituximab (R) in combination with chemotherapeutic agents, has led to the development of highly potent forms of chemoimmunotherapy. In the case of aggressive lymphomas, R-CHOP has been shown to be significantly superior to CHOP alone, both in elderly and younger patients. In stage III and IV indolent (follicular) lymphomas, rituximab/chemotherapy combinations achieve response rates in excess of 90%, and prolonged progression-free survival rates which, for the first time hold out hope of a cure. Monoclonal antibodies that can be coupled to radioisotopes open up new possibilities for potent radioimmunotherapy which look promising for effecting a cure or long-lasting palliation in additional proportion of the patients.

[Immunoglobulin substitution in patients with indolent non-Hodgkin's lymphoma]. / Immunglobulin-Substitution bei Patienten mit indolenten Non-Hodgkin-Lymphomen.

BACKGROUND: Infections are major complications in chronic lymphoproliferative disorders, among them indolent non-Hodgkin's lymphoma (iNHL) including chronic lymphocytic leukemia, follicular lymphoma and multiple myeloma.We report on a retrospective cohort analysis of outpatients with indolent non-Hodgkin's lymphoma who were treated in an oncology / hematology group practice and received intravenous polyvalent immunoglobulin G (IVIG) as supportive care. The aim was to describe the treated iNHL population, the course of therapy and the effects of IVIG administrations on the levels of immunoglobulin G (IgG), the incidence of infections and the survival time. PATIENTS AND METHOD: 57 patients with secondary iNHL antibody deficiencies (n = 46) or IgG subclass deficiencies (n = 11) who received IVIG substitution were included. Patients received median 11 IVIG doses with a mean dose of 28 g over a period of median 9.5 months. RESULTS: Mean IgG levels increased with IVIG substitution at about twice and then remained within the normal range. The incidence of infections decreased in 46 % of treated patients. Effects on survival could not be observed. Median overall survival was in the group of substituted patients 124 months (range 7-124), the control group had a median survival time of 96 months (range 3-129) (p = 0.537). CONCLUSION: IgG levels should be reviewed during IVIG substitution on a regular basis and dosage and intervals should be adjusted individually.

Limited sampling models for reliable estimation of etoposide area under the curve.

Limited sampling models are able to estimate the area under the concentration-time curve (AUC) from plasma concentrations measured at only a few time points. The purpose of this study was to establish a model estimating etoposide AUC independently of specific chemotherapy protocols, underlying malignancies, concomitant diseases and age. Pharmacokinetic parameters were measured in 30 patients treated with polychemotherapy including etoposide (80-150 mg/m2). Etoposide analysis was performed by thin layer chromatography and consecutive quantitative sample detection by 252Cf-plasma desorption mass spectrometry. Data from the first 15 patients formed the training set. Based on the training data, five different models were generated, with the multiple regression coefficient r ranging from 0.91 to 0.96. The following model was selected as "most accurate": AUC = 343 (min)C4h(micrograms/ml) + 650(min)C8h(micrograms/ml) + 1252 (min micrograms/mol), where C4h is the plasma concentration of etoposide at 4 h after the end of infusion and C8h at 8 h. This model was validated on the test set, comprising the data of the remaining 15 patients. The mean predictive error (MPE) was -0.2% and the root mean square predictive error (RMSE) was 4.7%. When used for a large number of patients, this practicable and simple model is an instrument for use in prospective studies, to measure a correlation between drug dosage and efficacy or toxicity of the drug.

A modified spectrophotometric test for nitroblue-tetrazolium reduction of granulocytes and monocytes and its application for testing inhibition of monocytes by serum components in tumor patients.

For evaluation of serum-factor involvement in monocyte function, we established a modified quantitative spectrophotometric-nitroblue tetrazolium (NBT) test. We investigated the stimulation of human peripheral monocytes and granulocytes by zymosan, endotoxin, and Corynebacterium parvum in vitro. In addition, polymorphonuclear neutrophil (PMN) function in a patient with non-Hodgkin lymphoma was studied during the course of polychemotherapy and intravenous application of Corynebacterium parvum (C. parvum). In non-Hodgkin lymphoma (n = 15) and bronchogenic carcinoma (n = 11) the NBT-reduction of autologous monocytes in presence of autologous serum in relation to a AB serum was decreased compared to a control group of age-matched healthy blood donors. The sera from patients with these neoplasms inhibited NBT-reduction of monocytes from healthy donors. This inhibition showed a correlation to the presence of immune complexes in patients with bronchogenic carcinoma.

Cleavage of IgG by elastase-like protease (ELP) of human polymorphonuclear leukocytes (PMN): isolation and characterization of Fab and Fc fragments and low-molecular-weight peptides. Stimulation of granulocyte function by ELP-derived Fab and Fc fragments.

The elastase-like protease (ELP) from human polymorphonuclear granulocytes (PNM) is able to split human IgG into Fab and Fc-like fragments and smaller peptides. These fragments are similar but not identical to those produced by papain. They differ in their electrophoretical mobility as well as in their molecular weights. Both ELP-Fab and papain-Fab show antigen-binding capacity. In contrast to papain-derived split products of IgG, the ELP-generated Fab and Fc fragments could enhance granulocyte function. Both ELP-Fab and ELP-Fc increase the spontaneous reduction of nitroblue-tetrazolium (NBT) in granulocytes dose-dependent in a homologous as well as in an autologous system. Furthermore, the ELP-derived Fab and Fc induce an active release of ELP by PMN. It could also be demonstrated that Fab as well as Fc increased the peroxidase activity in granulocytes.

Pharmacokinetics of high-dose etoposide after short-term infusion.

The pharmacokinetics of high-dose etoposide (total dose, 2100 mg/m2 divided into three doses given as 30-min infusions on 3 consecutive days) were studied in ten patients receiving high-dose combination chemotherapy followed by autologous bone marrow transplantation. In addition to etoposide, all subjects received 2 x 60 mg/kg cyclophosphamide and either 6 x 1,000 mg/m2 cytosine arabinoside (ara-C), 300 mg/m2 carmustine (BCNU), or 1,200 mg/m2 carboplatin. Plasma etoposide concentrations were determined by 252Cf plasma desorption mass spectrometry. In all, 27 measurements of kinetics in 10 patients were analyzed. According to graphic analysis, the plasma concentration versus time data for all postinfusion plasma etoposide values were fitted to a biexponential equation. The mean values for the calculated pharmacokinetic parameters were: t1/2 beta, 256 +/- 38 min; mean residence time (MRT), 346 +/- 47 min; AUC, 4,972 +/- 629 micrograms min ml-1 (normalized to a dose of 100 mg/m2); volume of distribution at steady state (Vdss), 6.6 +/- 1.2 l/m2; and clearance (CL), 20.4 +/- 2.4 ml min-1 m-2. A comparison of these values with standard-dose etoposide pharmacokinetics revealed that the distribution and elimination processes were not influenced by the dose over the range tested (70-700 mg/m2). Also, the coadministration of carboplatin did not lead to significant pharmacokinetic alterations. Although plasma etoposide concentrations at the time of bone marrow reinfusion (generally at 30 h after the last etoposide infusion) ranged between 0.57 and 2.39 micrograms/ml, all patients exhibited undelayed hematopoietic reconstitution.

Induction of complete haematological remission after monotherapy with anti-CD20 monoclonal antibody (RITUXIMAB) in a patient with alkylating agent resistant Waldenström's macroglobulinaemia.

Response of Waldenström's macroglobulinaemia to chemotherapy with alkylating agents is usually only transient. We report a case with marked bone marrow involvement and resistance to chemotherapy with alkylating agents. The patient was red cell and platelet transfusion dependent. Three weeks after rituximab-monotherapy, he achieved a complete haematological remission which is continuing 6 months after the end of therapy. Our case demonstrates that treatment with the unconjugated anti-CD20-monoclonal antibody (rituximab) may be a new powerful tool for a better treatment of Waldenström's macroglobulinaemia.

Cutaneous monoblastic leukemia as a first sign of relapse six years after autologous bone marrow transplantation for acute leukemia.

A patient with acute monoblastic leukemia (AML, M5A) was treated successfully in December 1987. In 1993 after 6 years in complete remission, she presented with an intracutaneous nodular mass on her right upper arm which was resected in toto and shown to be undifferentiated monoblastic leukemia. Two further chloroma lesions were excised in July 1994 and March 1995 respectively. Bone marrow cytology and histology always showed a continuing complete remission with no evidence of leukemia relapse. In July 1995 she presented with a disseminated skin infiltrate and a relapse with 80% monoblasts in the bone marrow. After one course of chemotherapy (Idarubicin/Ara-C), a second complete remission was achieved and her leukemic skin infiltrate disappeared completely. This case illustrates that chloromas of the skin can occur as late as 6 years after treatment for AML and also emphasizes that the occurrence of a chloroma does not necessarily mean immediate leukemia relapse. It also stresses that a second complete remission can be achieved with standard AML-induction therapy despite widespread leukemic skin infiltrates in such patients.

The role of decreased retinoblastoma protein expression in acute myelomonocytic and monoblastic leukemias.

The results of different investigators show that lack of p105 expression is relatively common in human myeloid leukemias, especially in monocytic leukemias. This suggests that loss of p105 expression could contribute to the altered growth control of these cells. So far no clear data exist which show that low p105 levels in AML blasts predict a poor therapy outcome. Therefore it is not very likely that p105 expression will become a strong prognostic factor for the different treatment strategies in AML.

Platinum sensitivity in a BRCA1 mutation carrier with advanced breast cancer.

Although BRCA1-associated breast carcinomas are frequently detected in nodal-negative stage, they typically present with an aggressive histopathological phenotype that is reflected by a poor prognosis and an increased risk for distant metastatic spread. Recent in vitro data suggest a high sensitivity of BRCA1-associated carcinomas to platinum-based chemotherapy and a lower sensitivity to anthracyclines and taxanes. This is explained by the key role of BRCA1 in DNA double-strand repair via homologous recombination, thereby leading to a higher sensitivity to DNA intercalating agents, such as platinum. Here we present the case of a woman suffering from BRCA1-associated metastatic breast carcinoma that was resistant to docetaxel, but responded strongly to cisplatin-containing chemotherapy. This supports the rationale of ongoing clinical studies.

Dose reduction of steroid premedication for paclitaxel: no increase of hypersensitivity reactions.

BACKGROUND: Premedication with dexamethasone, ranitidine and clemastine is mandatory for patients receiving paclitaxel to avoid hypersensitivity reactions. The proposed dexamethasone dose is 20 mg orally 12 and 6 h prior to paclitaxel infusion. With this premedication severe hypersensitivity reactions are reduced to 1-2% of the treated patients. Besides this oral schedule a single dose of dexamethasone, 40 mg given i.v., just prior to paclitaxel has been shown to be equally effective. In an attempt to reduce steroid-induced side effects, especially for patients receiving weekly paclitaxel protocols, we reduced the dexamethasone dose. PATIENTS AND METHODS: A total of 132 patients were treated on an outpatient basis with paclitaxel-containing protocols. Paclitaxel was given in doses of 135-175 mg/m(2) once every 3 weeks in 76 patients and/or with 100 mg/m(2) weekly in 70 patients. Dexamethasone premedication was given in a single dose (40, 20, 10 mg) as an infusion directly before paclitaxel. RESULTS: 0/46 patients receiving 40 mg dexamethasone premedication in 235 cycles and 0/48 patients receiving 20 mg dexamethasone premedication in 186 cycles experienced a severe hypersensitivity reaction. 1/52 patients receiving 10 mg dexamethasone in 480 applications developed a severe hypersensitivity reaction with bronchospasm, hypotension and supraventricular tachycardia shortly after her first paclitaxel infusion started. CONCLUSION: No increase of severe hypersensitivity reactions is seen when dexamethasone premedication is reduced to doses of 20 or even 10 mg prior to paclitaxel infusion.

The polyneuropathy associated with Waldenström's macroglobulinaemia can be treated effectively with chemotherapy and the anti-CD20 monoclonal antibody rituximab.

A 50-year-old male developed headache, impaired balance, visual defects and severe deafness. Ten months later he presented with markedly reduced power and tremor of his right arm. Waldenström's macroglobulinaemia (WM) with accompanying polyneuropathy was diagnosed. The patient received chemotherapy, which resulted in a partial improvement of the arm tremor. Subsequently, he was treated with rituximab (4 x 375 mg/m2), leading to complete resolution of the tremor and the paresis of his arm. Additionally, his headache and imbalance disappeared. Fifteen months after rituximab therapy he remained free of any neurological symptoms. This is the first report showing that WM-associated polyneuropathy can be treated effectively with a combination of chemotherapy and the anti-CD20 monoclonal antibody rituximab.

Isolation of Flavimonas oryzihabitans (CDC group Ve-2) from catheter-induced bacteremia in an immunocompromised patient.

Bacteria of the newly proposed genus and combination Flavimonas oryzihabitans, previously known as CDC group Ve-2 or Pseudomonas oryzihabitans, are uncommon pathogens. We report here the first isolation of the organism in Germany from a case of bacteremia and describe the phenotypic characteristics of the strain.

Peptide hormones in patients with acute leukaemia.

Paraneoplastic production and secretion of peptide hormones by numerous malignant tumours is a well-known phenomenon. The incidence of the production of six peptide hormones was evaluated in patients with acute leukaemia. Most often the calcitonin gene-related peptides were found to be elevated in sera at the time of diagnosis. The values evaluated for the hormones were: h-CT 46.7%, CGRP 51%, s-CT 20.7%, PTH 15.7%, beta-HCG 15%, and ACTH 11.6%. A significant coincidence of two or more hormones was not observed. In 83.4% of the patients increased concentrations of at least one of the six hormones were found. Clinical and biochemical parameters showed no influence on the serum levels of these peptides. Analysis of elevated hormone serum levels in subtypes of leukaemia revealed that the calcitonin-related hormones were significantly correlated to more immature forms of leukaemia such as AUL and M1. Synthesis of calcitonin gene-related peptides was also seen in established leukaemic cell lines and in buffy coat cells of untreated patients with acute leukaemia. This investigation provides further evidence that peptide hormone production in leukaemic blasts is a common finding. These results further suggest hormone production to be a universal concommitant of neoplasia. A possible influence of these peptide hormones on the biological behaviour of the malignant cells is discussed.

Successful long-term treatment of systemic lupus erythematosus with rituximab maintenance therapy.

Systemic lupus erythematosus (SLE) is a chronic, inflammatory autoimmune disease that may involve multiple organ systems. Treatment consists of immunosuppression, cytotoxic treatment, plasmapheresis and immunoglobuline therapy. Treatment of patients refractory to standard treatment approaches is difficult and results are poor. We describe a 39-year old patient with SLE suffering from grand mal epilepsy due to cerebral vasculopathy with positive lupus anticoagulant, who was refractory to standard treatment modalities. The patient was treated with the anti-CD20 monoclonal antibody rituximab (375 mg/m2 x 4, repeated at weekly intervals). Rituximab applications were delivered in October 2000, March 2001 and October 2001. Since March 2002 she has received maintenance therapy with rituximab 375 mg/m2 every three months. A second female with refractory SLE was treated successfully in April 2002 and receives maintenance therapy every three months. Both patients responded well to rituximab therapy. The first patient showed a major improvement of her clinical condition, and 30 months after the beginning of the rituximab therapy she is free of any symptoms. Inflammation parameters, ANA and lupus anticoagulant declined significantly after the treatment. The clinical condition of the second patient improved dramatically, all inflammation parameters normalized and her circulating immunocomplexes disappeared. In conclusion, rituximab maintenance treatment may be a new effective therapy in SLE.