Alternative vaccination against equine botulism (BoNT/C).

REASON FOR PERFORMING STUDY: In Europe the incidence of botulism in horses has increased in the last decade due to the growing popularity of haylage feeding. Recombinant vaccines are safer and less expensive to produce and are generally better tolerated than toxoids. OBJECTIVES: To investigate whether the recombinant C-terminal half of the heavy chain of the botulinum neurotoxin C (Hc BoNT/C) in combination with an immunstimulatory adjuvant is an appropriate vaccine candidate for horses by testing its efficacy to induce neutralising antibodies and by comparing its immunogenic properties and adverse reactions to a commercial toxoid vaccine. Formation of oedema and local pain reactions were assessed. ELISA and Western blot assay against Hc BoNT/C and testing of neutralising antibody induction in a mouse protection assay were used to evaluate the immune response. RESULTS: With the recombinant vaccine, only minor local swelling with full recovery after 5 days was noted after brisket injections. The toxoid vaccine produced local, painful reactions with longer recovery periods of up to 2 weeks. Horses vaccinated with either vaccine induced neutralising antibodies after the second booster vaccination, while seroconversion on ELISA and Western blot to Hc BoNT/C was apparent after the first recombinant vaccination, and at various time points in the vaccination schedule in horses that received commercial toxoid vaccine. CONCLUSION: The recombinant vaccine showed fewer adverse reactions compared to the only commercially available vaccine but induced similar concentrations of neutralising antibodies. There was no correlation between the serological response to Hc BoNT/C and the neutralising capacity of serum. POTENTIAL RELEVANCE: Recombinant Hc BoNT/C is an appropriate vaccine candidate to stimulate production of neutralising antibodies against botulinum neurotoxin C in horses and creates only minor local reactions at the injection site.

Epoetin alpha prevents anaemia and reduces transfusion requirements in patients undergoing primarily platinum-based chemotherapy for small cell lung cancer.

Anaemia commonly occurs in cancer patients receiving chemotherapy, often necessitating blood transfusion. This multicentre study was designed to evaluate the efficacy and safety of epoetin alpha in preventing the decline in haemoglobin (Hb) level, and to determine whether the transfusion requirement could be reduced, in patients receiving 4-6 cycles of primarily platinum-based combination cyclic chemotherapy for small cell lung cancer (SCLC). A total of 130 non-anaemic SCLC patients were randomized to receive no additional treatment (n = 44), epoetin alpha 150 IU kg(-1) subcutaneously (s.c.) three times a week (n = 42) or 300 IU kg(-1) s.c. three times a week (n = 44). Reductions in epoetin alpha dosage were made during the study if Hb level increased to >15 g dl(-1). The mean weekly dosage was 335 and 612 IU kg(-1), respectively, in the two active treatment groups. Significantly fewer (P < 0.05) epoetin alpha-treated patients experienced anaemia (Hb < 10 g dl(-1)) during the course of chemotherapy (300 IU kg(-1), 39%; 150 IU kg(-1), 48%; untreated, 66%). This was reflected in the significantly lower number of treated patients transfused [300 IU kg(-1), 20% (P< 0.001); 150 IU kg(-1), 45% (P< 0.05); untreated, 59%]. Epoetin alpha was well-tolerated, and there was no evidence of sustained, clinically significant, hypertension. In summary, epoetin alpha is effective and well-tolerated in maintaining Hb level and reducing transfusion requirement in patients undergoing cyclic chemotherapy for SCLC.

[Field study with a vaccine against enzootic pneumonia of swine]. / Feldversuche mit einer Vakzine gegen die Enzootische Pneumonie (EP) der Schweine.

The EP vaccine Stellamune Myco was tested in 4 different trials. In a first trial, the daily weight increase and the incidence of lung lesions and their degree of severity were compared in non-vaccinated and vaccinated pigs originating from a herd infected with M. hyopneumoniae. The daily weight increases of the vaccinated animals were almost 60 g above that of the non-vaccinated and the number of altered lungs and the severity of the lung lesions was smaller in the vaccinated group. The effects were statistically different. In a second trial, no lesions were observed in 60% of the vaccinated animals. In the non-vaccinated group, the proportion was only about 35%. More severe lung lesions were only present in the non-vaccinated animals. In a third trial, it was observed that the animals originating from infected herds may excrete mycoplasmas despite the vaccination. In a fourth trial, it was determined that SPF piglets were not protected with the vaccination against an infection caused by M. hyopneumoniae.

Combined-modality treatment of small-cell lung cancer: randomized comparison of three induction chemotherapies followed by maintenance chemotherapy with or without radiotherapy to the chest. Swiss Group for Clinical Cancer Research (SAKK).

BACKGROUND: From 1980 to 1983 the Swiss Group for Clinical Cancer Research (SAKK) performed a randomised phase III trial in patients with small-cell lung cancer with the objective of improving the results of induction chemotherapy and defining the role of consolidating chest irradiation. PATIENTS AND METHODS: Patients were initially randomised to induction arms AVP (adriamycin, etoposide and cisplatin given every four weeks for four cycles), EVA (cyclophosphamide, etoposide and adriamycin given every four weeks for four cycles) or MOC/AVP (methotrexate, vincristine, cyclophosphamide alternating with adriamycin, etoposide and cisplatin given for two cycles). All patients received prophylactic cranial irradiation with 30 Gy, and after four months of induction chemotherapy were randomized to maintenance chemotherapy with or without consolidating chest irradiation. The patients in the combined-modality maintenance arm first received radiation therapy to the chest (45 Gy) followed by MOC/EVA chemotherapy. RESULTS: 266 patients were eligible and evaluable. An overall response rate of 70% with 21% of complete remissions, a median survival of 9.3 months and survival of 8% of the patients at two years were observed. The highest objective response rate was achieved with the AVP-induction chemotherapy with an 80% response rate and 32% complete remissions. Similar results were achieved with the alternating regimen of MOC/AVP. In contrast, patients treated with the EVA induction regimen had significantly lower overall remission (56%) and complete remission rates (7%). The role of consolidating chest irradiation could not be clarified in limited-disease patients due to the small number of them who were randomised to the maintenance part of the study. However, in patients with extensive disease in partial remission after induction treatment, combined maintenance therapy had a more significant adverse effect on survival than maintenance chemotherapy alone (median survival in the maintenance phase of 148 days versus 239 days, p = 0.011). CONCLUSION: We conclude that the combination of adriamycin, etoposide and cisplatin is an active induction treatment. Consolidating chest irradiation is contraindicated in patients with extensive disease in partial remission after induction when given in a sequential manner, as in our trial.

[Clinical aspects in oral, pharyngeal and laryngeal carcinoma--results of an overall Swiss cohort study]. / Klinik und Diagnose beim Mundhöhlen-, Pharynx- und Larynxkarzinom--Ergebnisse einer gesamtschweizerischen Erhebung.

Squamous cell carcinomas of the oral cavity, pharynx and larynx cause early symptoms and are fairly accessible. Nevertheless, in more than half of cases they are diagnosed at an advanced stage. This paper identifies patients at high risk of developing one of these carcinomas, describes the typical clinical findings and shows how, with a high index of suspicion and a proper examination technique, diagnosis at an earlier stage could be achieved. The study is based on the data of 636 patients with squamous cell carcinoma of the oral cavity (174 patients), oropharynx (177), hypopharynx (97), and larynx (188). 87% of the patients were male, and 90% were aged between 40 and 80 years. 85% of the patients smoked and drank alcohol regularly. The key symptoms were pain, dysphagia, hoarseness, a painless neck mass, or a visible ulcerating lesion. On average a 4-month period elapsed from the onset of symptoms to the histological diagnosis. The diagnostic delay was significantly shorter in patients with pain or visible organic changes (ulcerating lesions, neck masses) than in patients with functional symptoms (dysphagia and hoarseness).

"Fatigue and malaise" as a quality-of-life indicator in small-cell lung cancer patients. The Swiss Group for Clinical Cancer Research (SAKK)

"Fatigue and malaise" (FM) is a frequent, non-specific symptom of cancer patients caused by the disease, its treatment and psychological distress. Since comprehensive quality of life assessment is often not feasible in multicentre clinical trials, short, but clinically relevant, quality of life indicators have to be defined. In a representative subsample of 127 patients in a phase-III randomized small-cell lung cancer trial comparing two different regimens of combination chemotherapy, quality of life was assessed at the beginning of each of the six treatment cycles with a self-rating questionnaire including an early version of the EORTC questionnaire, a mood adjective check list (Bf-S) and a single linear-analogue self-assessment scale (LASA) measuring general well-being. FM, measured with a five-item Likert subscale of the EORTC questionnaire, showed moderate to high intercorrelations with other EORTC subscales assessing disease symptoms, toxicity of treatment, role functioning, personal functioning, restriction of social activity, psychological distress, emotional (Bf-S) and general well-being (LASA). At baseline, FM was one of the most pronounced symptoms. Over the six cycles 43%-31% of the patients complained of moderate to severe fatigue. Over the first two cycles FM tended to decrease, slightly increasing during cycles 3 and 4 and decreasing again before cycle 6. In a multiple regression analysis over the six cycles, 53% of the variance of FM was explained by patient-rated symptoms of disease and toxicity (disease alone: 43%; toxicity alone: 35%). Initial performance status, previous weight loss, treatment arm, cycle number and age predicted the scores of FM over the six cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors associated with transfusion requirements during treatment for acute myelogenous leukemia.

Supportive care is a prerequisite for intensive chemotherapy in leukemic patients. Little has been published about quantitative aspects of red blood cell and platelet transfusions. We evaluated transfusion requirements and factors associated with observed differences in 206 patients undergoing initial induction consolidation chemotherapy for newly diagnosed acute myelogenous leukemia. All patients were treated during a 5-year period in 12 hospitals on a common protocol of the Swiss Study Group for Clinical Cancer Research (SAKK). Protocol 30/85 comprises a double induction and one course of consolidation. Of 206 registered patients, 199 were evaluable; 118 of 199 (59%) patients entered completed all three cycles of chemotherapy. These 118 patients received a median (range) of 18 (3-44) units of red blood cells and 12 (2-61) platelet transfusions during 112 (70-129) days of hospitalization. Patients with a hemoglobin > 10 g/l, platelets > 100 x 10(9)/l, and white blood cell counts < 5 x 10(9)/l at diagnosis received fewer transfusions than patients with less favorable blood counts during the first cycle of chemotherapy (p < 0.05). Patients with FAB subtype M3 received more platelet transfusions during the first cycle. Female patients received more platelet transfusions than male patients. In multivariate analyses the participating center was the most important single factor associated with the number of red cell and platelet concentrates given per patient and cycle (p < 0.05), the number of days in hospital (p < 0.05), and the risk of premature withdrawal from the study. These data define factors associated with transfusion requirements in patients treated for newly diagnosed AML. They include severity and subtype of disease at diagnosis, age and sex of the patients, and the participating institution. Results suggest that medical decision-making varies from center to center. The participating institution is strongly associated with differences in transfusion requirements, hospitalization time, and premature withdrawal from study. Leukemia trials tend to focus on the prospective evaluation of chemotherapy or growth factors. Our results suggest that other variables, such as management strategies, should be included for prospective analysis.

[Ovarian carcinoma: current therapeutic aspects. A review]. / Das Ovarialkarzinom: neue therapeutische Aspekte. Eine Ubersicht.

Ovarian cancer is the leading cause of gynaecologic cancer death and the fourth most frequent cause of cancer death in women. 70% of all ovarian cancers will be diagnosed only at an advanced stage of the disease despite the improvements in diagnostic tools. Standard therapeutic concepts and new therapeutic modalities are discussed. Staging laparotomy with cytoreductive surgery is the most important part of initial patient management. Second-look operation has recently come under criticism, as it probably offers only minor therapeutic benefit. However, it remains the golden rule for evaluating different therapy modalities in the setting of a clinical trial. After surgery, chemotherapy is indicated for all patients with ovarian cancer FIGO stage III and IV. The question whether all patients with stage I and II disease need additional treatment remains unresolved. The standard regimen for patients with advanced ovarian cancer consists of six months' chemotherapy with a combination of cisplatin and an alkylating agent. Current cisplatin containing regimens achieve a clinical response rate of 60-80% and a documented pathologic complete response rate of 30% overall. Despite higher overall response rates and increased disease-free survival rates with cisplatinum combinations, long term survival is not significantly altered. Investigative approaches with intraperitoneal chemotherapy, biologic response modifiers and drug resistance modifiers may open new therapeutic avenues for this challenging disease. Radiotherapy (open field technique) also represents a highly active and curative treatment modality for certain ovarian cancer patients. Nowadays radiotherapy is mainly used as adjuvant treatment for patients with low risk early stage disease and as consolidation treatment for patients with complete remission after chemotherapy and second-look operation.

Combination chemotherapy with mitomycin, vindesine, and cisplatin for non-small cell lung cancer. Association of antitumor activity with initial tumor burden and treatment center.

From 1984 through 1986, 205 patients with non-small cell lung cancer were entered into a group-wide trial of the Swiss Group for Clinical Cancer Research (SAKK). This trial evaluated the combination of mitomycin (8 mg/m2 intravenously [IV] on day 1), vindesine (3 mg/m2 IV on days 1 and 8), and cisplatin (60 mg/m2 IV on day 1) with forced diuresis, repeated every 4 weeks (MiViP regimen). One hundred eighty-three patients were evaluable. Six complete and 69 partial responses were documented for an overall response rate of 41% (95% confidence interval, 34% to 50%). In the multivariate analysis the strongest predictors for response were the participating institution and the number of initially involved organ sites. The estimated median time to progression for patients with a complete response, partial response, or stable disease was 155 days (estimated inter-quartile range, 99 to 258 days). In the multivariate analysis the time to progression was significantly associated with the number of involved organ sites (P = 0.041). The estimated median survival time for the 183 evaluable patients was 239 days (estimated inter-quartile range, 137 to 436 days). In univariate and multivariate analyses performance status, number of involved organ sites, pretreatment status with radiation therapy, and participating institution were all significantly associated with survival. The principal toxicities were myelosuppression and nausea and vomiting with 16% of the patients refusing further treatment after a median of four cycles of chemotherapy. In conclusion, the MiViP regimen was an active combination chemotherapy in patients with non-small cell lung cancer in a large trial performed by the SAKK. The prognostic value of the participating institution and the number of organ sites involved by metastatic deposits in non-small cell lung cancer needs further investigation.

[Loco-regional recurrence following surgery of breast carcinoma: prognostic factors and therapeutic consequences]. / Das loko-regionale Rezidiv nach operiertem Mammakarzinom: prognostische Faktoren und therapeutische Konsequenzen.

The course following local relapse after mastectomy was studied prospectively in 225 women. Factors significantly influencing the further course were determined. On the whole the prognosis was relatively good, with a projected 5-year relapse-free survival of 47%, a median time interval of 53 months until development of distant metastases, and an estimated death rate of 41% after 5 years. The most important factor influencing the incidence and time interval until appearance of distant metastases is the axillary lymph node status at the time of mastectomy. N0 patients have a much better prognosis than N+ patients in univariate as well as multivariate analysis. Other factors in univariate analysis which play a role in either the incidence of distant metastases or overall survival include estrogen receptor content, site of the local relapse (skin or regional lymph nodes), time interval between mastectomy and the occurrence of the local relapse, and number of tumor nodules in the local relapse. In multivariate analysis virtually the only really independent prognostic factors are primarily the initial axillary lymph node status for survival free of distant metastases and the time interval from mastectomy to local relapse for overall survival.