Weekly docetaxel monotherapy for advanced gastric or esophagogastric junction cancer. Results of a phase II study in elderly patients or patients with impaired performance status.

BACKGROUND: Three-weekly docetaxel is active in patients with advanced esophagogastric cancer but myelosuppression may make this schedule unsuitable for some patient groups such as elderly, pretreated, or poor performance status patients. PATIENTS AND METHODS: Eligible patients were chemonaive with Karnofsky index < or =70% and/or had received prior platinum-based chemotherapy. Docetaxel 35 mg/m(2) was administered on days 1, 8, 15, 22, 29, and 36 of a 49-day cycle. The primary endpoint was disease stabilization rate. RESULTS: Of 46 patients (median age, 68.5 years; 47% > or =70 years) included, 87% had Karnofsky index < or =70 and 50% had prior treatment. The safety profile was acceptable. Principal grade 3/4 toxicities were leukopenia (9%) and fatigue (14%). Fifteen patients experienced no progression for > or =100 days (disease stabilization rate: 36%). Overall response rate was 9%; median overall survival was 7.0 months. CONCLUSIONS: Weekly docetaxel was well tolerated and achieved disease stabilization in one-third of difficult-to-treat patients.

[Ischemic anastomotic bowel perforation during treatment with bevacizumab 10 months after surgery]. / Ischämische Anastomosenperforation im Bereich einer Ileotransversostomie unter Therapie mit Bevacizumab.

BACKGROUND: Bevacizumab (Avastin) is a monoclonal antibody against vascular endothelial growth factor (VEGF) receptor that has demonstrated increased overall survival when added to standard chemotherapy regimens in patients with metastatic colorectal cancer. Gastrointestinal perforation is a known risk factor of unknown etiology associated with the use of bevacizumab. OBJECTIVE: We report a 61-year-old woman with adenocarcinoma of the colon ascendens who underwent hemicolectomy and adjuvant chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin. Eight months after the operation, we started therapy with bevacizumab combined with irinotecan, 5-fluorouracil, and leucovorin due to disease progression. Two months after completion of this therapy, ischemic anastomotic bowel perforation occurred and a resection of the anastomosis was performed. Because of anastomotic insufficiency 8 days later, a further revision had to be done and the terminal ileum and the colon were brought out through a stoma. DISCUSSION: This case is unusual because the time interval between the primary operation and the application of bevacizumab is regarded as safe with regard to the risk of perforation. An ischemic genesis of the perforation was considered on the basis of the histopathological workup. In case of perforations during therapy with bevacizumab, a safe surgical approach should be preferred, i.e., a transient stoma instead of a primary reconstruction of the bowel passage.

A randomized study comparing interferon (IFN alpha) plus low-dose cytarabine and interferon plus hydroxyurea (HU) in early chronic-phase chronic myeloid leukemia (CML).

This multicenter randomized phase III study was designed to compare the efficacy and toxicity of IFN alpha-2c (3.5 MU/d) in combination with either araC (10 mg/m(2) d1-10) or hydroxyurea (HU: 25 mg/kg per day) in newly diagnosed CML patients. A total of 114 patients were randomized. Following a median observation period of 36 (range 1-73) months the major cytogenetic response rates were 25 and 27% and the 4-year survival probabilities 62.5 and 63% for the araC and HU group, respectively. While the overall toxicity profile was comparable between both groups, patients in the HU arm exhibited a slightly higher degree of WHO grades 3 and 4 non-hematological toxicities.

[Kidney calculus episode in a supernumerary 3rd kidney]. / Steinepisode in überzähliger dritter Niere.

Supernumerary kidney is a rare renal anomaly. As a distinct encapsulated parenchymatous mass, this free accessory organ has a separate blood supply and excretory duct system. We report on a patient who presented with an acute episode of abdominopelvic pain, secondary to hydronephrosis of a third kidney, situated in the pelvis behind the bladder. Modern diagnostic methods assisted in the conservative management of this well functioning third kidney.

Interferon-alpha for the treatment of elderly patients with chronic myeloid leukaemia.

The present retrospective analysis is based on data of 213 patients with chronic myeloid leukaemia (CML). They were treated with interferon (IFN)alpha-2C (Berofor) at daily doses of 3.5 MU subcutaneously (s.c.), alone or in combination with low-dose ara-C or hydroxyurea, according to four consecutive studies of the Austrian CML Study Group. Comparisons were made between 41 patients aged > or = 60 years and 172 younger patients. The elderly patients (median: 64 years; range: 60-73) showed similar pretreatment characteristics compared with the younger group, but included a higher percentage of Sokal Stage three (51 vs 20%). Median observation periods were similar (38 vs 39 months), whereas the duration of IFNalpha treatment was shorter in the elderly group (median 57 vs 42 weeks). The rate of overall haematological responses (73 vs 78%) and complete haematological response (44 vs 54%), was similar in both cohorts. Differences seen in partial (5 vs 12%) and complete cytogenetic response (10 vs 13%), were not statistically significant, but a tendency in favour of the younger cohort had to be noted. Summing up, in elderly patients acceptable rates of haematological and cytogentic response can be expected after treatment with IFNalpha alone or in combination with LD ara-C or HU.

Interferon-alpha-2C and LD ara-C for the treatment of patients with CML: results of the Austrian multi-center phase II study.

Small pilot studies of patients with CML have reported on encouraging response rates after treatment with interferon-alpha (IFNalpha) in combination with low-dose cytosine arabinoside (LD ara-C). We therefore initiated a multi-center phase II trial in order to investigate the efficacy and tolerability of this combination in newly diagnosed patients with Ph-positive chronic myelogenous leukemia (CML). Eighty-four patients were treated with IFN-alpha-2c at daily subcutaneous doses of 3.5 MU and LD ara-C added subcutaneously for 10 days every month at a dose of 10 mg/m2, following an initial reduction of WBC to less than 20 x 10(9)/l with hydroxyurea (HU). Within a median observation period of 28 (5-59) months the patients received a median of 7 (1-35) IFNalpha and LD ara-C cycles. Treatment was stopped due to side effects in 16 cases (19%) and to primary or secondary treatment failure in 38 cases (45%). In 45 patients (54%) complete hematological response (CHR) was achieved; in 39 patients (46%) cytogenetic responses including 15 (18%) complete cytogenetic responses (CHR) were observed. Median duration of cytogenetic responses was 15 months. Relapses were seen in 8/15 patients (53%) with complete cytogenetic remission (CCR), in 3/6 patients (50%) with partial cytogenetic response and in 9/18 patients (50%) with minor cytogenetic response. In conclusion, the combination of IFNalpha and LD ara-C resulted in encouraging rates of hematological and cytogenetic responses in patients with CML with low to moderate toxicity.

Comparison of clinical efficacy and toxicity of conventional and optimum biological response modifying doses of interferon alpha-2C in the treatment of hairy cell leukemia: a retrospective analysis of 39 patients.

Hairy cell leukemia (HCL) has been shown to be extraordinarily sensitive to treatment with alpha-interferon (IFN). In order to define clinically effective IFN doses associated with minimal toxicity, the therapeutic efficacy and side effects of recombinant IFN-alpha-2C treatment of HCL were compared for two different dose regimens: 18 patients (group A) received conventional doses of recombinant IFN-alpha-2C (2 x 10(6)U/m2) for a median time of 35 weeks (range 26-52 weeks), and 21 patients (group B) received optimum biological response-modifying doses of IFN-alpha-2C (0.2-0.6 x 10(6)U/m2) for a median time of 31 weeks (range 12-52 weeks). Interferon was administered daily subcutaneously for 3 months and then every second or third day. Induction of neopterin excretion was chosen as the marker for definition of biological response. The smallest IFN dose causing maximum in vivo induction of biosynthesis of the GTP-degradation product neopterin was deemed "biologically optimal." Both dose regimens were effective, but the low-dose regimen was almost free of toxicity. Thus, in HCL patients alpha-IFN related toxicity can be separated from its antineoplastic activity. Low doses of alpha-IFN should be considered for treatment of HCL patients who develop toxic side effects and for primary treatment of HCL patients with severe cytopenia.

Interferon-alpha-2 in the treatment of idiopathic myelofibrosis.

We investigated the effect of human recombinant DNA-derived IFN-alpha-2 given in a dose of 1-2 X 10(6) units daily by subcutaneous injection to five patients with advanced idiopathic myelofibrosis (IM). Transfusion dependent anemia and symptomatic splenomegaly were taken as inclusion criteria for this pilot study. Two patients succumbed, one and three months after starting interferon-treatment because of pneumonia and traumatic cranial injury, respectively. While on IFN-treatment no improvement of cytopenia or reduction of splenomegaly was seen in four of the patients. In one patient, however, the requirement for erythrocyte transfusions decreased from 5 to 1.7 monthly upon IFN-treatment. After two, four and six months respectively IFN-treatment had to be stopped in these cases because of progressive thrombocytopenia and/or neutropenia. These observations suggest, that IFN-alpha might be of only marginal value in the treatment of advanced idiopathic myelofibrosis.

[Rhabdomyolysis as a late complication of anesthesia--a case of malignant hyperthermia?]. / Rhabdomyolyse als Spätkomplikation einer Anästhesie--ein Fall maligner Hyperthermie?

Rhabdomyolysis is usually known to the anaesthetist, who may be confronted with this acute, life-threatening complication during anaesthesia. However, also the medical specialist ought to be familiar with the clinical picture of malignant hyperthermia, since rhabdomyolysis may occur as a late post-anaesthetic complication. Even in oligo-symptomatic and protracted cases of malignant hyperthermia, the case history, electromyogram, exclusion of other possible causes of rhabdomyolysis and, if possible, muscle biopsy contribute to the confirmation of the diagnosis. If a muscle biopsy is not available then a platelet bioassay may substantiate the diagnosis.

[Pump-guided continuous subcutaneous opiate infusion for the treatment of the most severe pain]. / Pumpengesteuerte kontinuierliche subkutane Opiat-Infusion zur Behandlung schwerster Schmerzen.

The continuous subcutaneous infusion of opiate, a new approach to the alleviation of severe chronic pain, has been carried out using a pump system normally employed for the infusion of insulin. Relapses of pain can be controlled with bolus doses. This mode of application was compared with conventional therapy in 11 patients. All patients were free of pain during the continuous infusion, but none showed a satisfactory response during conventional treatment. The improved response under continuous opiate infusion was attained with much lower doses and thus with fewer side effects. The procedure is therefore highly effective and well tolerated.

[Results of a phase II study on the treatment of hairy cell leukemias with various doses of alpha-2-recombinant interferon]. / Ergebnisse einer Phase-II-Studie zur Behandlung von Haarzell-Leukämien mit unterschiedlichen Dosen von alpha-2-rekombinantem Interferon.

Hairy-cell leukemia has been shown to be extraordinary sensitive to treatment with alpha-interferon. In order to define clinically effective interferon doses associated with minimal toxicity two different dose regimens were applied in this clinical trial: firstly, a conventional dose schedule, and secondly, a biologically defined dose regimen. For dose finding in the latter group, neopterin, a GTP degradation product produced by macrophages under control of interferon, was chosen. Six patients (Group A) received conventional doses of recombinant interferon--alpha-2 (rIFN-alpha-2) 3 X 10(6) U/sqm/daily by the subcutaneous route. Five patients (Group B) were treated with the minimal dose of rIFN-alpha-2 which had previously been shown to induce maximum neopterin levels in urine. Already interferon doses in the range of 3 to 5 X 10(5) U/sqm2/daily administered subcutaneously proved to be sufficient for triggering maximum neopterin excretion in the urine. After six months of interferon treatment all patients were evaluable. At this time both doses regimens proved to be effective in terms of their anti-leukemic activity, but differed significantly in toxicity, which was only seen in Group A patients.

[Long-term osteoporosis with multiple fractures as the early monosymptomatic stage of multiple myeloma]. / Langjährige Osteoporose mit multiplen Frakturen als monosymptomatisches Frühstadium eines multiplen Myeloms.

A 44 year old man with kappa-light plasmacytoma is presented who had been treated for osteoporosis and multiple bone fractures since 12 years. On admittance he had a rapidly progressive myeloma kidney and an extensive extramedullary tumor within the pelvis. Remission was induced using combination chemotherapy according to the VMCP-protocol. It is discussed that the long-lasting osteoporosis of the present case represents an unusually long, monosymptomatic early stage of a multiple myeloma rather than an independent primary disease.

[Long-term survival and fatal late relapse in acute leukaemia in adults]. / Langzeitüberlebende und letale Spätrezidive bei akuter Leukämie des Erwachsenen.

This study comprises 187 patients aged over 15 years with acute leukaemia, diagnosed and treated between the years 1969 and 1978. Fourteen (7.5%) survived for more than 5 years after diagnosis. In this group of survivors there were 7 patients with AML and 6 with ALL--corresponding to 8.9 and 21.4% of each collective, respectively--and 1 patient with PML. Four patients (28.6%) died after a survival time exceeding 5 years, 1 patient with AML as a result of a gastric carcinoma and the 3 other patients (1 AML, 2 ALL) of the original disease. Hence, survival times over several years do not necessarily mean real cures. From an analysis of our data, no factor correlating with long-term survival was identifiable. In terms of clinical-diagnostic parameters the group of late relapses was also heterogeneous.

[Myocardial infarct during ergotamine medication in a young man with normal coronary arteries]. / Myokardinfarkt unter Ergotamin-Medikation bei einem Jugendlichen mit normalen Koronararterien.

Normal coronary vessels and an akinetic anterolateral wall segment were found in a 24-year-old patient on angiography 10 months after a clinically established myocardial infarction. As the patient had been on a high-dosage medication with ergotamine for two years and as all risk factors for coronary sclerosis as well as evidence of other cardiac diseases were lacking, it seems appropriate to assume that myocardial ischaemia had been caused by coronary spasms.

[Long-term survivors of acute lymphatic leukemia in adults]. / Langzeitüberlebende bei akuter lymphatischer Leukämie des Erwachsenen.

A long-term survival study was carried out in a group of 28 adult patients with acute lymphathic leukemia. The complete remission rate was 67.8%, the 50% survival rate is 21.5 months and 41 months in those with complete remissions. Six of 28 patients are long-term survivors and are living at least 5 years after diagnosis. There was a significant majority of female patients among the long-term survivors, with a female to male ratio of 4:2. The 50% survival rate of female patients (n = 11) was 42.5 months and thus considerably higher compared with the corresponding male patients (n = 17, 50% survival rate 7 months). No further clinical or hematological parameters of prognostic relevance were found as a common feature of the long-term survivor group.

[Acute leukemias in elderly patients (author's transl)]. / Unreifzellige Leukämien im fortgeschrittenen Lebensalter.

We conducted an investigation of 186 randomly selected acute adult leukemia patients in order to examine how far age and subtype of leukemia can be correlated with survival rate. The diagnosis of leukemia was established by cytochemical and cytomorphological techniques. There was an increased frequency of acute myelogenic leukemias in older patients. The age group of the 61-90 year old showed a significant decrease in the survival rate, but at the same time in this age group there was a higher frequency of leukemia types with poor prognosis. Early deaths were correlated with advanced age of patients. There were no long time survivors (with survival rates longer than 4 years after diagnosis) above the age of 57.