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.

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 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.

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.

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.

[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.

[The mitral valve prolapse syndrome and its complications (author's transl)]. / Zur Problematik des Mitralklappenprolapssyndroms unter besonderer Berücksichtigung der Komplikationen.

Out of 1800 patients examined for valvular heart disease, 19 were found to have the mitral valve prolapse syndrome (MVPS). The relevant literature is reviewed and the epidemiology and aetiology of the disease are discussed. 50% of the patients had a history of endomyocarditis. The special diagnostic value of echocardiography is emphasized. Sudden death (observed in 2 young patients) and the grave complication of bacterial endocarditis (observed in 3 patients and usually caused by Streptococcus viridans) can occur in this condition. Prophylactic therapy with beta-blocking drugs and antibiotics seems warranted. The case history of one patient with MVPS under observation for eight years, who developed bacterial endocarditis from a dental focus is reported in greater detail as a typical case.

[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.

[Complete occlusion of the aortic arch in an adult (author's transl)]. / Kompletter Verschluss des Aortenbogens beim Erwachsenen.

This paper reports the case of a 55-year-old patient with complete obstruction of the aorta between the left common carotid artery and the left subclavian artery. The arterial blood supply to the lower half of the body is provided by extensive collateral networks in the region of the right hemithorax, the neck and the base of the brain. Only 10 similar cases appear to have been described in the literature; our patient seems to be the oldest so far.

[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.

[Cytochemical aspects in bone marrow cells in macrocytic anemias]. / Zytochemische Befunde an den Knochenmarkzellen bei makrozytären Anämien.

Cytochemical investigations are useful for the characterization of different kinds of macrocytic anemias. Vitamin B12 and folate defects or chronic alcoholic myelopathy, induce in the erythroblasts cytochemical patterns which can be distinguished from those seen in preleukemia, erythroleukemia, or in drug induced toxic anemia. Tests for alpha-naphthol-acetate-esterase, for acid phosphatase, for iron, and for polysaccharides (PAS-stain), are especially valuable for these diagnostic procedures.

[Atypical, severe pancytopenia in chronic myelomonocytic leukemia (author's transl)]. / Atypische, schwere Panzytopenie bei chronischer myelomonozytärer Leukämie.

Among 17 patients with non acute monocytic (CMoL) and myelomonocytic leukemia (CMML) one patient presented with atypical findings and an unusual clinical course. Prominent massive pancytopenia had occurred ever since the diagnosis was established. To our knowledge this symptom has not been described in cases with CMML and CMoL. Splenectomy afforded temporary improvement of the anemia but induced sustained, marked thrombocytosis. An unusually prolonged survival time of 44 months was achieved, presumably by the continuous, careful replacement of blood, the splenectomy and the relinquishment of cytotoxic therapy. A gradual, continuously developing blastic crisis and finally the transition to an acute leukemia were observed.

[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.

[Clinical and cytological differences in adult acute lymphatic and acute undifferentiated leukemia]. / Klinische und zytologische Unterschiede bei akuten lymphatischen und akuten undifferenzierten Leukämien des Erwachsenen

The usefulness for clinical purposes of the distinction of acute undifferentiated (AUL) and acute lymphocytic leukemia (ALL) is suggested by the following observations: 1. Maturation from AUL to ALL has not been observed. Transformation of ALL to AUL has been reported i.e. less of cytoplasmic polysaccharides; however this seems rather to be the effect of cytotoxic therapy and not a real change of the cytological type. 2. Significant differences among ALL and AUL can be noted as far as the therapeutic response is concerned: All of the 9 patients with ALL but only 2 out of 9 patients with AUL went into remission. The mean survival of the cases with ALL amounts to 34, that of AUL only to 4 months. Out of the patients with ALL 4 patients are still alive in persistant first remission after 77, 57, 36 and 28 months. 3. ALL occurs most frequently in young adults (mean age of 21 patients: 31.7 years): AUL is more frequent in elderly patients (Mean age of 18 patients: 57.6 years). 4. In our material ALL did never occur consequent to a typical preluekemic stage, which was followed either by myeloblastic, monocytic, erythroleukemic or undifferentiated leukemias.

[Prolymphocytic and hairy cell leukemias as special forms of chronic lymphatic leukemia]. / Prolymphozytäre und Haarzellen-Leukämie als Sonderformen der chronischen lymphatischen Leukämie.

Cytochemical and immunological studies were performed on "hairy" cells from 5 patients. The results, primarily the detection of surface immunoglobulins after incubation in immunoglobulin-free medium support the hypothesis that hairy cells are B-cells. Further parameters for B-cell lineage are the failing suppression of unspecific esterases by NaF, the presence of tartrate-resistant acid phosphatase and the absence of phagocytic capacity and glass adherence (skin window). A lysozyme could not be demonstrated. Of two patients with prolymphocytic leukemia one was characterized as T- and one as B-cell leukemia. Therefore, the prolymphocytic leukemia has to be discussed as intermediate form of ALL and CLL. In both patients the therapeutic results were discouraging with cytostatics (e. g. chlorambucil), splenectomy is considered as the treatment of choice.

[Subacute and chronic monocytic leukemia: diagnostic and clinical problems]. / Subakute und chronische monozytäre Leukämie: Diagnostische und klinische Problematik.

The authors report on 16 cases of either subacute (SMML) or chronic (CMML) myelomonocytic leukemia as well as chronic monocytic leukemia (CMoL). All these cases were oligoblastic and, according to their clinical course, they could be termed as smouldering leukemias. The chronic types affected mainly males. The diagnostic cytomorphological and cytochemical criteria are discussed. Erythro- and thrombocytopoiesis were distinctly less impaired than in acute leukemias (AL). The leucocyte count in the peripheral blood of the SMML cases was within the normal range. Hepato- and splenomegaly were markedly increased as compared to AL. According to our materials leukemic skin infiltrations were less frequent in CMoL, CMML and SMML than in acute monocytic leukemias. In each of the three types of leukemia discussed monocytic leukemic cells could be readily identified by cytochemical tests and usually showed fairly normal maturation. In accordance with these observations lysozyme levels in urine and serum usually were strongly increased. The patients in the CMML and CMoL groups showed a mean survival of more than 13 months (2 out of 7 are still alive), whereas the SMML patients survived an average of 8 months. Deaths were frequently due to advanced age rather than to leukemia. In other cases a terminal accumulation of blasts marked a transition to acute leukemia. During the smouldering phase of the disease no beneficial effect of combined chemotherapy could be noted. Supportive and symptomatic therapy might improve length and quality of survival.