Search

Cancer-related fatigue (CRF) during and after tumor therapy influences all aspects of life and lowers performance and quality of life. Regular CRF screening and diagnostic evaluation are important factors in the care of patients. This article presents strategies for recognizing and treating CRF. Multiprofessional and personalized therapies can improve CRF. Outpatient and inpatient rehabilitative strategies should be implemented after completion of tumor therapy., (© 2024. Springer-Verlag GmbH Deutschland, ein Teil von Springer Nature.)

Cancer-related fatigue (CRF) is a common, burdensome, debilitating subjective sense of tiredness or exhaustion in patients with cancer. The pathogenesis is assumed to be multifactorial with CRF being a final common pathway. Among other things, treatment with immune checkpoint inhibitors (ICI) is also associated with CRF. However, the toxic adverse events of ICI are not inevitably the only cause for CRF. Therefore, the diagnostic procedure should address other possible influencing factors, e.g., somatic, mental, cognitive, and psychosocial causes. To manage CRF evidence-based, causal, and symptomatic therapies are available. The key condition to manage CRF is active listening and shared decision making (SDM) with the goal to select those interventions from the broad spectrum of therapies that are best suited for the particular patient and their life circumstances. Providing information about ICI and CRF to reassure patients is already an effective intervention., (© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2021.)

Hintergrund: Die onkologische Rehabilitation ist integraler Bestandteil der Versorgung krebskranker Menschen. Nach einer dreiwöchigen stationären Rehabilitation mit multimodalem und integrativem Ansatz wurden die Effekte auf Belastungen und Lebensqualität der Patienten überprüft. Patienten und Methoden: 74 Krebspatienten erhielten ein komplexes Therapieprogramm, das Therapien zur Verbesserung der funktionalen Gesundheit, zur Reduktion psychosozialer Belastungen und komplementäre Massnahmen beinhaltete. Der Erfolg der Therapie wurde mit validierten Fragebögen am Abschluss der Rehabilitation (T2) und 3 Monate danach (T3) bestimmt. Ergebnisse: Es zeigte sich eine signifikante Besserung von Distress, Angst, Depression, Fatigue und Lebensqualitätsfunktionsskalen zum Zeitpunkt T2 und T3. Von T2 nach T3 war der Therapieeffekt rückläufig, ohne die Werte von T1 zu erreichen. Schlussfolgerungen: Eine multimodale, integrative onkologische Rehabilitation führt zu einer über 3 Monate anhaltenden Besserung des subjektiven Befindens der Patienten. Dieses Therapiekonzept sollte in einer Folgestudie mit einer Standardrehabilitation verglichen werden., Background: Oncological rehabilitation is an integral part in the care of cancer patients. Following an inpatient rehabilitation of 3 weeks’ duration with multidimensional and integrative components, the effects on distress and quality of life were measured., Patients and Methods: 74 cancer patients received a complex treatment program, including treatments for improvement of functional health, reduction of psychosocial distress and complementary therapies. The treatment outcome was evaluated with validated questionnaires at the end of the rehabilitation (T2) and 3 months thereafter (T3)., Results: We observed significant improvement of distress, anxiety, depression, fatigue and quality of life at T2 and T3. In the interval from T2 to T3, the treatment effect was declining, without reaching the values of T1., Conclusions: A multidimensional integrative oncological rehabilitation improves the subjective condition of the patients over a 3-month period. This treatment concept should be tested in a comparative study against standard rehabilitation., (© 2019 S. Karger AG, Basel.)

Background: Cellulitis is commonly treated in the emergency department (ED). Patients who present with cellulitis incur significant health care costs and may be overtreated with antibiotics. The accurate diagnosis and treatment of cellulitis plays an important role in cost-effective, high-quality medical care, as well as appropriate antibiotic utilization., Objective: We aim to describe common fallacies regarding cellulitis. We present 10 myths that result in misdiagnosis, overtreatment, or inappropriate empiric management of cellulitis. Clinical presentation, including swelling and redness, is explored in depth, along with incidence of community-acquired methicillin-resistance Staphylococcus aureus, management of tick bites, and effective antibiotic therapy for cellulitis., Discussion: Patients are often treated for cellulitis unnecessarily or inappropriately. Awareness of these myths will help guide providers in clinical decision making in order to effectively tailor treatment for these infections., Conclusions: Cellulitis is not as simple as it might seem, and is commonly misdiagnosed in the ED. Noninfectious causes of local symptoms, including lymphedema, venous stasis, and deep vein thrombosis need to be considered. Cellulitis should be treated with empiric antimicrobial therapy based on patient risk factors and regional susceptibility patterns. This review will assist providers in managing cellulitis and avoiding treatment errors that lead to high costs, unwanted side effects for patients, and overuse of antibiotics., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives/hypothesis: Statistically significant differences in health-related quality of life (HRQL) are not always clinically relevant. It is also plausible that patients perceive other changes to be relevant than health professionals do. The objective of this study was to find thresholds for HRQL that laryngectomees consider to be clinically relevant 1 year after surgery, (i.e., the level of HRQL that patients rate as satisfactory). A second aim was to investigate how many laryngectomized patients reached those targets., Study Design: Multicenter cross-sectional study., Methods: A total of 28 patients 1 year following laryngectomy and 24 healthcare professionals (HCPs) defined target values for the QLQ-C30 and QLQ-H&N35. In another sample of 157 laryngectomized patients 1 year following laryngectomy, we determined what percentage of patients reached these thresholds., Results: Patients are the most accepting of sensory impairments (56.5), coughing (53.6), and dyspnea (44.0), whereas constipation (9.1) and nausea/vomiting (10.7) were rated as being the most troublesome symptoms. HCPs assessed more of the studied complaints as being tolerable than patients did, especially in psychosocial domains. Between 34.5% (senses) and 86.5% (constipation) of the reference group hit the predefined targets at different scales., Conclusions: Symptoms caused by disease are easier for patients to live with than more general nonspecific symptoms. Taking into account that some adverse effects of disease or therapy are partially irreversible, target values additional to changes of HRQL can be helpful when interpreting data., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Unlabelled: Secondary lymphedema is one of the most frequent long-term side effects affecting up to 30% of all breast cancer patients after local surgical and radiation treatment. Destruction of the lymphatic system causes a progressive and chronic condition with functional impairments and disabilities limiting patients in their daily activities and involving nearly all aspects of their quality of life. Also, problems in the occupational area may be caused by lymphedema. The need for improving oncological management for early diagnosis and referral for effective treatment of lymphedema is a major goal of breast cancer heath care while survival improves., Method: A systematic consensus process was performed involving all relevant partners and providers of lymphedema health care to develop a practical documentation concept and make recommendations according to the evidence of clinical studies and currently available guidelines., Results: A practical concept of documentation with defined assessment points was developed for evaluation and monitoring of lymphedema, which included the assessment of quality of life parameters with recognised instruments by the patient themselves. Consensus recommendations for the postoperative management, prevention, treatment and follow-up of breast cancer patients along a clinical algorithm for in- and outpatient care were finalized., Conclusion: With improved survival, long-term side effects with major impact on quality of life become a most important end point criteria of oncological treatment. The clearly defined documentation concept and the comprehensive recommendations for lymphedema management may assist clinicians and patients to make timely decisions about in- and outpatient health care practice to optimize the interface between acute medicine and rehabilitation. Patients' compliance with treatment and prevention routines will be as important as ensuring the continuity of care. A longitudinal prospective study evaluating the effectiveness and efficacy of the consensus recommendation is currently being implemented.

Background: Cancer-related fatigue is the most disabling symptom experienced by breast cancer patients following the cancer treatment. The positive effects of physical activity in the rehabilitation of breast cancer patients are documented in several studies. In a randomized controlled study the effects of a structured physical training program on fatigue and health-related quality of life were evaluated., Patients and Methods: 63 breast cancer patients with cancer-related chronic fatigue were randomized at the beginning of the inpatient rehabilitation. The control group received the standard complex rehabilitation program, the intervention group a structured physical training program and additional muscle strength and aerobic exercises. The effects of the treatment were evaluated by questionnaires at the start of rehabilitation (t1), end of rehabilitation (t2), and 3 months after t2 (t3). Isometric muscle strength and aerobic capacity were evaluated at t1 and t2., Results: There was an improvement of muscle strength at the end of rehabilitation for both groups. The increase from t1 to t2 was significantly higher for the training group. The scores for global quality of life, physical well-being, and functionality increased from t1 to t2, but further improvement in the follow-up (t3) was only observed in the training group. The cancer-related fatigue was significantly reduced in the training group from t1 to t3, however, not in the control group., Conclusions: Structured physical training programs initiated during inpatient rehabilitation and continuously practiced in the time thereafter can improve symptoms of chronic fatigue and quality of life in breast cancer patients.

Background: Major endpoint for the assessment of a complex inpatient rehabilitation program is the health-related quality of life. In a prospective longitudinal study we evaluated the subjective well-being of breast cancer patients by different methods., Patients and Methods: 183 breast cancer patients were asked to complete six different questionnaires at three different time points: t1: start of treatment, t2: end of treatment, t3: 3 months after t2., Results: In the Hospital Anxiety and Depression Scale (HADS-D) we observed high mean scores for anxiety (8.73) and depression (5.55), as compared to a healthy control population (5.8 and 3.34, respectively). There was a significant improvement for both scores at t2 (6.84 and 4.77, respectively) and for anxiety at t3 (7.68). This was confirmed by the FBK questionnaire showing a significant decrease of the psychological distress in the t1/t2 and t1/t3 time periods as well. The global health score of the QLQ-C30 instrument increased significantly at the end of the rehabilitation and was maintained at the 3-month follow-up. This was true for most of the functional subscales as well. Older widowed women with 3-4 accompanying diseases had the most profit from the program. Using the Perceived Adjustment to Chronic Illness Scale (PACIS), we observed significantly less effort of coping with the illness at t2 and t3., Conclusions: At the end of a complex rehabilitation program for breast cancer patients, the health-related quality of life improved in several domains. While after a 3-month follow-up the scores were still better than before the treatment, anxiety and depression increased again. Therefore, the good results of the rehabilitation program should be maintained by continuous ambulatory treatment., (Copyright 2001 S. Karger GmbH, Freiburg)

A rehabilitation program for women with high risk for breast cancer or known hereditary breast carcinoma is described. The rehabilitation uses complex and interdisciplinary therapeutic interventions to improve symptoms, functional deficits and disease and treatment related psychologic distress. An essential component of the rehabilitation is an educational program with up-to-date information about the possibilities and limitations of genetic testing and recommendations about primary and secondary prevention. Suggestions for risk reduction as primary prevention are discussed. This rehabilitation program should be implemented in an effective follow-up care for women genetically susceptible to breast cancer.

Budotitane [cis-diethoxybis(1-phenylbutane-1,3-dionato)titanium (IV)] is a novel inorganic metal complex. Preclinical studies in established screening models indicate considerable antitumor activity. We have performed a clinical Phase I and pharmacokinetic trial with budotitane administered as i.v. infusion twice weekly. The starting dose of 100 mg/m2 was derived from a prior single dose Phase I study. Eighteen patients with solid tumors refractory to all other known treatment modalities were entered. 17 patients had received prior chemotherapy. Dose levels ranged from 100 mg/m2 to 230 mg/m2, with a total of 122 budotitane infusions administered. Neither leuko- nor thrombocytopenia were observed. 2/5 pts at 180 mg/m2 and 2/4 pts at 230 mg/m2 developed a 3-fold increase of reticulocytes without signs of hemolysis or bleeding. Nonhematologic toxicity was moderate at doses of < or = 180 mg/m2. Fifteen patients reported loss of taste at the day of infusion. At 230 mg/m2, 2/4 pts developed WHO grade 3 cardiac arrhythmias with polytope premature ventricular beats and nonsustained ventricular tachycardia. A limited pharmacokinetic analysis was performed at dose levels 180 mg/m2 and 230 mg/m2. At 180 mg/m2, Cmax was 2.9 +/- 1.2 microg/ml, t1/2 78.7 +/- 24.4 h, Cltot 25.3 +/- 4.6 ml/min and AUC 203 +/- 71.5 h x microg/ml. At 230 mg/m2, Cmax was 2.2 +/- 0.8 microg/ml, t1/2 59.3 +/- 12.1 h, Cltot 44.9 +/- 23.6 ml/min and AUC was 183 +/- 90.4 h x microg/ml. No objective tumor response was observed. We conclude that the maximum tolerated dose of budotitane administered twice weekly is 230 mg/m2, the dose limiting toxicity is cardiac arrhythmia. Further evaluation of the nature of the cardiac toxicities observed is warranted. Using this schedule, 180 mg/m2 is a safe dose for subsequent clinical studies.

Tumor necrosis factor (TNF) is a cytokine produced in vivo by activated macrophages and monocytes with pleiotropic effects on normal and malignant cells. TNF is cytotoxic to several tumor cell lines in vitro and in vivo. Phase I and phase II trials have been conducted to determine toxicity to humans and to evaluate responses. Recent investigations will be reviewed. Despite promising results in vitro and in vivo, data from systemic administration in the treatment of malignancies have been disappointing. Local administration has been successful. Therefore, we suggest that future efforts concerning TNF administration in the treatment of malignancies should aim at local treatment.

In 1989, a prospective randomized multicenter study was initiated in order to determine the safety and efficacy of oral clodronate in myeloma patients. The primary objective of this long-term trial is to evaluate whether supportive clodronate is able to prevent or retard the progression of bone disease and reduce the occurrence of characteristic complications: pain, pathologic fractures, and hypercalcemia. We now report first results as an interim analysis, including data obtained from 26 patients (total number of Tübingen patients n = 36) who entered the study at the Medizinische Universitätsklinik Tübingen. Patients were randomized to receive either chemotherapy alone (melphalan 15 mg/m2 i.v. on day 1 and prednisolone 60 mg/m2 orally on days 1-4 every 4 weeks (control group) or in combination with 1600 mg clodronate/day orally as a single dose for a period of at least 1 year. Repeated radiologic examinations in addition to hematologic and biochemical analysis were performed in order to evaluate the skeletal status with respect to lytic bone lesions and osteoporosis and the course of serum M protein and light chain excretion into urine. Clodronate treatment resulted in a significant decrease of serum calcium concentrations and of biochemical indices for bone resorption. No clodronate-related toxicity or hypocalcemia was observed. In patients treated with chemotherapy alone, this effect was less marked and discontinuous. Clodronate-treated patients developed fewer progressive bone lesions (significant for lytic, not for osteoporotic lesions). No hypercalcemic episodes occurred in the clodronate-treated patients, but there were six episodes in the control group. Whereas the number of vertebral fractures was evidently less is clodronate-treated patients, three of those patients suffered from multiple fractures of long bones and ribs. All together, 12 pathologic fractures occurred in five clodronate-treated patients, whereas in the control group 23 pathologic fractures occurred in the same number of patients during the whole observation period. The final analysis of all multicenter included patients should clarify these findings. There was a significant finding that clodronate proved to have an analgesic effect.

Between 1986 and 1988, 81 patients with high grade malignant non-Hodgkin lymphoma according to the Kiel classification were treated with the VIM-Bleo/CHOP-regimen: etoposide 100 mg/m2 intravenously on days 1-3, ifosfamide 1.5 g/m2 intravenously days 1-5 with mesna for prophylaxis of cystitis, methotrexate 30 mg/m2 intravenously on days 3, bleomycin 10 mg intravenously on days 8 and 15, cyclophosphamide 750 mg/m2 day 22, doxorubicin 50 mg/m2 day 22, vincristine 1.4 mg/m2 on day 22, and prednisolone 100 mg postoperatively on days 1-5 and 22-26. Cycles were repeated four times beginning on day 43. Regions with bulky disease were irradiated after chemotherapy. 36 patients (44%) had stage II, 12 (15%) stage III and 33 (41%) stage IV disease. B-symptoms were present in 49% of patients. Serum lactate dehydrogenase activity was elevated in 53%. Overall, 59 patients (73%) achieved a complete and 14 (17%) a partial remission. 8 (9%) had stable or progressive disease. After a median follow up of 30 months thus far, probability of long-term relapse free survival is 66% for patients in complete remission. Overall survival is 72% at 24 months. Toxicity from treatment was very low with leukopenia being the main side effect. Major infections were observed in only 2% of cycles with one treatment related death. VIM-Bleo/CHOP is a well tolerated regimen with remission rates in the range of other, more toxic regimens. However, cyclic alternating treatment did not improve results as compared with repeated treatment with a single standard protocol.

In a phase II study, the efficacy and toxicity of human recombinant tumor necrosis factor (rh TNF-alpha) were evaluated in patients with advanced colorectal carcinoma. Rh TNF-alpha was given as short term infusion at a dose of 3 x 10(5) U/m2 on three successive days. Treatment was repeated after a two week interval. The response was evaluated after four treatment cycles. In 15 patients entering the study, we found one partial response, one stable disease, 9 progressive diseases, and four patients who were not evaluable for tumor remission. There were numerous side effects of the treatment, mainly fever, chills, loss of appetite, leukopenia, and hepatotoxicity. In this regimen, rh TNF-alpha does not suggest a therapeutic advantage for treatment of advanced colorectal carcinoma.

Experimental results suggest synergistic activity of interferon with different cytotoxic agents, including vinblastine. Both interferon and vinblastine have shown synergistic activity against renal cell carcinoma in the human stem cell assay. In this multicenter phase II study, patients with documented advanced renal cell carcinoma were treated with interferon alpha-2a at a dose of 18 x 10(6) IU i.m. 3 days per week and vinblastine 0.1 mg/kg body weight i.v. every 3 weeks. Combination therapy was given for 6 months except patients with progressive disease. We observed 6/34 (17.6%) partial remissions and 16/34 (47%) no changes. Five out of six responses were seen in pulmonary metastases with a median response duration of 10 months and a median survival for the responders of 17 months. A dose reduction because of interferon toxicity was necessary in 60% of the treated patients. The main side effects were fever and influenza-like symptoms of different intensity in 70% of the patients, which decreased during the treatment periods. This trial demonstrates modest but definite antitumor activity of the combination of interferon alpha-2a/vinblastine. In comparison with single agent therapy we did not observe improved remission rates for the combination treatment.

The course of the disease in a patient with multiple endocrine neoplasia type IIa over a period of seven years is described. In spite of multiple diagnostic procedures, only a bone marrow biopsy was able to prove metastatic disease. All therapeutic measures, such as combination chemotherapy, sandostatin, bromocriptine, and 131Iodinemethylendiphosphonate-therapy were not effective in reducing tumor load or symptoms.

In a multicentre phase II trial, 20 patients with advanced pancreatic carcinoma were treated with 5-fluorouracil, 4-epidoxorubicin and mitomycin C, in which 4-epidoxorubicin was administered by escalated dose and split course (FEM II). From among 12 patients evaluable for response, 2 partial and 1 minimal remission were observed, suggesting a response rate of 25%. Four patients (30%) showed a no change and 5 progression. The median survival of all patients was 3.4 months, of the responders 8.4 months, of those with no change 5.2, and of those showing progression 3.4 months. Considerable nausea/vomiting and leukopenia was observed. The preliminary data suggest that the FEM II regimen does not offer any progress in terms of efficacy, survival and toxicity for advanced pancreatic carcinoma.

Implants of fetal stomach and colon under the kidney capsule of syngeneic, and H-2 compatible and H-2 incompatible allogeneic mice were examined histologically at different time intervals after the procedure. According to the time of implantation typical inflammatory changes were seen in syngeneic stomach and colon implants, which resembled changes seen in chronic atrophic gastritis and chronic ulcerative colitis. Immunofluorescence studies showed that the host developed antibodies against fetal antigens, while there was no evidence for cellular immune response to fetal syngeneic antigens with the direct leukocyte migration inhibition test. Possible explanations for these results are discussed.

Reports suggesting that delta 9-tetrahydrocannabinol (THC) had a potent antiemetic effect in patients treated with cancer chemotherapeutic agents led to the synthesis of other cannabinol derivatives with possibly less side effects. We report here our initial observations with the antiemetic levonantradol in 12 patients with advanced solid tumors receiving cytotoxic polychemotherapy. All patients had a history of vomiting and nausea without successful treatment with standard antiemetic drugs in previous, identical chemotherapy cycles. No other antiemetic or psychoactive drugs were given. Patients received 1 mg levonantradol i.m. 2 hours before as well as 2 and 6 hours after cytotoxic treatment. When compared to the last course of chemotherapy with alternate antiemetic drugs, we found that 11/12 patients had less nausea and vomiting when treated with levonantradol. 8/12 Patients considered the antiemetic treatment with levonantradol better than the one given before. The following side effects were observed: 4 patients complained of pain and local irritation after injection. 2 patients showed a fall in blood pressure, especially orthostatic hypotension. 8 patients complained of sedation and drowsiness. 7 patients experienced psychic side effects, such as decrease of vigilance and reaction, altered sense of timing, body image distortions and even depersonalization. Levonantradol is a potent antiemetic drug but its applicability, especially in outpatients, may be complicated by a high incidence of side effects.

27 patients with advanced colorectal cancer were treated in a phase-II trial with high dose sequential methotrexate (MTX), 5-fluorouracil (5-FU), and folinic acid (FA). Following a 4 h infusion of 800 mg/m2 MTX and a 4 h interval, 1,500 mg/m2 5-FU and 200 mg/m2 FA were given as a 24 h infusion. Out of 23 evaluable patients we observed one partial remission and 9 disease stabilizations. Median survival time of all patients was 10.4 months. Overall toxicity was low. In comparison to a previous trial we did not observe better treatment results by adding high dose FA to a sequential MTX/5-FU schedule.

Twenty four patients with high grade malignant NHL (stage II 8, stage III 4, stage IV 12 patients respectively) were treated with a response-oriented regimen: Treatment was initiated according to the CHOP-protocol. Patients achieving at least a partial remission after 2 and a complete remission (CR) after 4 cycles were continued on CHOP to a total of 9 cycles. Patients not meeting these criteria were switched to a combination of Etoposide, Ifosfamide, Methotrexate, and Bleomycin (VIM-Bleo). With CHOP treatment, 16 patients (67%) achieved a CR. Of the remaining 8, 7 were treated with VIM-Bleo; 5 of these entered CR for a overall CR rate of 21/24 (88%). With a median follow up of 28 months 7 patients relapsed: 6 relapses occurred in patients with a rapid initial response and treated only with CHOP. We conclude, that there is a significant risk of relapse even in patients readily responding to CHOP and that consolidation therapy with a non cross-resistant regimen may improve results in these patients.

Twenty-four colorectal carcinomas were assayed for estrogen and progestin receptors by sucrose gradient centrifugation. Most biopsies were either completely estrogen receptor negative or displayed low titers of specific estrogen binding. Only three tumors demonstrated moderate estrogen binding activity (10-18 fmol/mg cytosol protein). In four tumors specific progestin binding exceeded 20 fmol/mg protein. Only a minor subset of the binders sedimented at 8S. Twenty-one colorectal tumors examined for the presence of glucocorticoid receptors were found to be receptor positive, without exception. Biopsies from normal colorectal mucosa displayed minute quantities of specific 8S estrogen and progestin binding, but significant titers of specific glucocorticoid binding. Our findings support the hypothesis that estrogens and progestins are unlikely to play a major role in endocrine control of colorectal neoplasms. The role of glucocorticoids in growth control of colorectal neoplasms remains to be defined.

The results of combined radiation and chemotherapy for the treatment of gastric carcinoma are reviewed. A small amount of postoperative adjuvant combined treatments of the curatively resected gastric carcinoma was performed which do not suggest any advantage of treatment compared to observation. For locally advanced and unresectable gastric carcinoma 5-fluorouracil or ftorafur was administered simultaneously to local irradiation in several phase-II studies. The response rates of 37%-58% and one year survival of 45%-72% do not suggest an advantage of combined modality compared to the one way treatment. The FAM, FAMe or FAB regimen was also used and obviously do not improve the results of combined modality treatment. A small but well conducted prospective randomized trials compared radiotherapy with and without chemotherapy or chemotherapy with and without radiotherapy. Recent results from different cooperative groups failed to improve the treatment results in terms of response and survival.

Adjuvant parenteral nutrition of tumor patients receiving cytotoxic chemotherapy offers many potential advantages. There are some randomized studies with few cases looking at the effect of parenteral nutrition on tumor response and toxicity. In an own prospective randomized study on parenteral nutrition of colorectal cancer patients an increase of tumor response, prolongation of survival, or reduction of toxicity could not be achieved. Published controlled studies are discussed in a literature review. Parenteral nutrition of tumor patients receiving chemotherapy is not principally advantageous and should be restricted to special clinical situations.

In a randomized crossover study 57 cancer patients receiving chemotherapy with high emetic potential were treated with low-dose levonantradol or standard-dose metoclopramide and crossed over to the other antiemetic drug in the next identical chemotherapy cycle. In the 45 patients evaluable for treatment response the antiemetic efficacy of levonantradol was significantly better: 62% had less nausea and 58% less vomiting, as against 11% and 16%, respectively, with metoclopramide. Patient preference for antiemetic treatment was levonantradol in 49% and metoclopramide in 22% of cases. Levonantradol treatment was accompanied by a relatively high incidence of side-effects (71%) compared with metoclopramide (29%). The antiemetic efficacy of each single drug was incomplete in most cases of this trial, and antiemetic combination therapy is recommended for further trials.

Newer aspects of therapeutic potentials of cannabis and cannabinoids are reviewed. The major active constituent of cannabis sativa, delta-9-tetrahydrocannabinol and synthetic cannabinoids are evaluated in several clinical trials on their antiemetic efficacy in cancer chemotherapy induced vomiting. 80% of patients refractory to standard antiemetic treatment could be improved with the synthetic cannabinoid levonantradol. Other therapeutic effects, which are presently investigated in clinical trials are analgesia, antispasticity, anticonvulsion and the reduction of intraocular pressure in glaucoma. The future goal of cannabinoid research is the separation between specific pharmacologic activities and undesirable psychotropic effects.

Two cases in adults with recurrent staphylococcal infections associated with abnormal granulocytic chemotaxis and hyperimmunoglobulinaemia E (Job's syndrome) are described. The pathophysiological mechanisms seems to consist of an abnormal IgE reaction against staphylococcal antigens causing secondary abnormality of granulocyte function. Abnormal cellular immune function was demonstrated in vitro and in vivo. Corticosteroid administration at first proved effective in both patients. One patient developed Hodgkin's disease of the mixed type in the course of the disease.

Random allocation of 22 patients with benign and malignant diseases with neutrophil counts of up to 1 X 10(9)/l blood and probably infection-caused fever of more than 38 degrees C to intravenous treatment with one of the following antibiotic combinations was performed: carbenicillin (6 g/m(2) . 6 h) plus sisomicin (45 g/m2 . 6 h) or mezlocillin (3 g/m2 . 6 h) plus sisomicin (45 g/m2 . 6 h). Both combinations were tolerated equally well. Patients became afebrile in 16 out of 23 treatment periods. Seven out of 11 patients responded to carbenicillin - sisomicin, and 9 out of 12 to mezlocillin - sisomicin. Mezlocillin thus leads to equal success of treatment in febrile neutropenia as the double dose of carbenicillin when both antibiotics are combined with the same aminoglycoside.

An autosomal erythrocytosis, inherited as a dominant, occurred in seven members of a family. The propositus was first diagnosed as having erythrocytosis at 26 years of age. He had headaches and marked plethora. Polycythaemia vera and secondary erythrocytosis of known cause were excluded. Erythropoietin level was not elevated. Two of his three children were also found to have erythrocytosis. As in this family, the disease is characterized in middle age by hypertension, cardiovascular and thromboembolic phenomena, as well as abnormal bleeding. For over eight years the propositus has been successfully treated with repeated venous blood lettings.

54 patients with high grade malignant NHL (stage II 19, stage III 10, stage IV 25 patients, medium age 56 years) were treated in an ongoing study with the VIM-Bleo/CHOP-regimen: Etoposide 100 mg/m2 i.v. days 1-3, Ifosfamide 1.5 g/m2 i.v. days 1-5 with Mesna for prophylaxis of cystitis, Methotrexate 30 mg/m2 i.v. day 3, Bleomycin 10 mg i.v. days 8 and 15, Cyclophosphamide 750 mg/m2 day 22, Adriamycin 50 mg/m2 day 22, Vincristine 1.4 mg/m2 day 22 and prednisolone 100 mg po days 1-5 and 22-26. Cycles were repeated on day 43. After completion of therapy (4 cycles of VIM-Bleo/CHOP), 27 out of 35 patients (77%) were in complete remission. 6 patients (17%) had a partial remission and 2 (6%) progressive disease. After a median follow up of 8 months so far, 6 relapses occurred. Probability of survival at 12 months is 82%. Toxicity of treatment was very low with leukopenia being the main side effect. Only in 2 cycles (3%), major infections were observed. Nausea and vomiting were severe only in 4% of patients. We conclude that VIM-Bleo/CHOP is a well tolerated regimen with good remission rates in high grade malignant NHL. However, longer follow up is necessary for a final evaluation.

The antitumor activity of budotitane was investigated in three different tumor systems--the transplantable murine ascitic-colon-adenocarcinoma MAC 15A, the TD-osteosarcoma of the rat, and the intramuscularly transplanted murine sarcoma 180. Marked inhibition of tumor growth was observed in the intramuscularly transplanted sarcoma 180, and cure rates of 50-80% were achieved in the colon adenocarcinoma MAC 15A. In contrast to these findings, bulotitane was inactive in the transplantable TD-osteosarcoma of the rat. Preliminary mutagenicity studies with the Salmonella typhimurium/mammalian microsome assay of Ames did not show any evidence of mutagenicity for the compound. The first results of the phase I clinical trials showed mild hepatotoxicity at a dose level of 15 mg/kg, dose-limiting nephrotoxicity at 21 mg/kg, and a reversible impairment of the sense of taste, beginning at a dose of 9 mg/kg.

20 patients with malignant tumours with severe gastrointestinal side effects during cancer chemotherapy refractory to standard antiemetic drugs were treated with the cannabinoid levonantradol in a second identical chemotherapy course. 17 patients (85%) has less nausea and vomiting, 5 had a total relief of symptoms, and 8 had a reduction of frequency of vomiting of 50% or more. Side effects were frequent, whereby fatigue, dizziness (12/20) and psychical side effects (8/20) were found to be the most uncomfortable.

In a phase-III study in non-Hodgkin's lymphoma of low malignancy we compared a combination therapy with vincristine (COP) with a vindesine combination (CEP). Remission rates, duration of remission and survival was favorable for the CEP combination without reaching the level of significance. The peripheral neurotoxicity of grade 2 and 3 according to WHO criteria was observed more frequently with vincristine. The vincristine-induced neurotoxicity in 6 patients was not impaired when a change was made to vindesine treatment.

Doxifluridine, a new fluoropyrimidine analog, was administered to 21 patients with advanced colorectal carcinoma. The starting dose was 1.0 g/m2 given over 24 h for 90 consecutive days as a continuous infusion. Due to severe skin reactions (hand-foot syndrome), the dose was reduced stepwise to 0.75 g/m2/day. Twenty patients were evaluable for efficacy, one had an early non-toxic death. Seven out of 20 (35%) showed a partial response; disease stabilization was observed in 10 patients (50%) and three showed progressive disease after 3 months of treatment. All 17 patients who achieved a partial response or a stabilization of disease were treated until progressive disease was documented and some had therapy up to 46 weeks. Toxicity was minimal and mainly defined as hand-foot syndrome which occurred in 50% of the patients of whom three experienced severe reaction. There was no myelosuppression, renal or liver dysfunction, no cardiac alterations and only one patient experienced severe dizziness. Doxifluridine is active in advanced colorectal carcinoma when the drug is given as a continuous infusion for 90 consecutive days at a daily dose of 0.75 g/m2.

In a multi-center study of 77 patients with gastric carcinoma and metastases, the effects of combined 5-fluorouracil and carmustine with or without adriamycin (FB vs FAB) were compared. There was no significant difference between the two treatment groups as to rate of response or survival time, response to treatment was 20% (FB) and 24% (FAB), including "no change" 52% and 56%, respectively. But median survival time among the responders (partial remission and clinical improvement) and of the patients with unchanged findings was significantly longer (8.4 or 7.4 months, respectively) than that among patients with progression (4.5 months). Analysis of prognostic factors in terms of survival curves revealed no difference between patients with or without measurable tumor parameters, with or without local recurrences or liver metastases. However, there was a statistically significant worsening of prognosis for patients whose initial general state was reduced, who had lung metastases or increased WBC counts. Side effects were relatively mild with both therapy regimens, except for alopecia with FAB. After the second treatment cycle myelosuppression was more marked with FAB than FB.

Ten patients with advanced renal carcinoma were treated by ifosfamide (50-60 mg/kd/day x 5 days). The treatment was repeated every 4 weeks and continued until progression appeared. Two patients came into partial remission, two had subjective improvement, and six did not respond. Seven patients developed acute psychopathological symptoms during the first ifosfamide-cycle. Five patients had visual and paranoid hallucinations, four patients were completely confused. Follow-up for up to 10 weeks showed a persisting organic brain syndrome in five patients.

In a phase II trial 46 patients with advanced gastric carcinoma were treated with FEM combination chemotherapy (5-fluorouracil, 4-epidoxorubicin and mitomycin C) in which 4-epidoxorubicin was administered by escalated dose and split course (FEM II). Twenty-nine patients with measurable disease were evaluable for response. One complete remission and 7 partial remissions were achieved, suggesting an overall response rate of 28%; 2 minimal responses (7%) and 9 patients with no change were observed (31%); 10 patients had tumor progression (34%). Median survival time for all patients was 6.2 months, for patients with CR + PR + MR 16.2 months, for patients with no change 8.4 months, and with tumor progression 3.5 months. WHO grade 2 and 3 leukopenia appeared in 6%, thrombocytopenia in 0% and alopecia in 27% of the patients after the first cycle. Nausea and vomiting grade 2 and 3 were seen in 21%. Comparing these results with our earlier data achieved with FEM I, FEM II showed a tendency towards better response and survival, and subjective toxicity (nausea/vomiting) was significantly reduced. Therefore, in our opinion FEM II is preferable for practical use.

In 361 Sprague-Dawley rats autochthonous colorectal carcinomas were induced by intrarectal application of the carcinogen AMMN. Tumor-bearing animals were treated with a synthetic thioether-lysophospholipid (TLP) derivative and in combination chemotherapy with 5-fluorouracil (5-FU) and carmustine (BCNU). There was no difference in the survival time of treated and untreated animals. The median large-bowel tumor weight was significantly lower in the TLP/5-FU and TLP/5-FU/BCNU combination therapy groups than in the control groups. Transient hepatotoxicity was observed in the high-dosage (50 mg/kg body weight twice weekly) TLP group. This study confirmed the relative resistance of AMMN-induced colorectal carcinomas to antineoplastic treatment.

The cooperative oncology group for Chemotherapy of Gastrointestinal Tumors (CGT) retrospectively examined 139 patients with metastatic colorectal cancer for prognostic factors. Clinical characteristics, tumor parameters, and blood parameters were investigated for prognostic explanation of survival from the start of chemotherapy for the advanced disease. A combination of a univariate regression and a multivariate step down procedure with Cox's regression model led to the identification of performance status, sex, white blood count and, to a lesser degree, blood sedimentation rate and albumin as important prognostic factors. Based on these variables an individual risk score was calculated for each patient.