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December 2006
M. Tokar, D. Bobilev, S. Ariad and D.B. Geffen

Background: Disseminated intravascular coagulation associated with malignant bone marrow involvement has been described as a rare complication of gastric carcinoma and most patients die within 1–4 weeks. Effective chemotherapy of the underlying malignancy may be the only way to control acute DIC[1].

Objectives: To assess the benefit of infusional 5-fluorouracil as the primary treatment of metastatic gastric carcinoma and DIC at diagnosis.

Methods: From February 2001 to January 2005, six women (median age 48 years) with gastric carcinoma who presented with diffuse bone metastases and acute DIC were treated in our department. Diagnosis was based on primary gastric and bone marrow biopsies. DIC was confirmed by laboratory findings. Initial treatment consisted of infusional 5FU[2] 200 mg/m2/day. When the bleeding tendency stopped, cisplatin 60 mg/m2 and epirubicin 50 mg/m2 given every 3 weeks were added.

Results: Within one week of starting the treatment, the clinical and laboratory signs of acute DIC were resolved in five of six patients. Upon clinical improvement, five patients subsequently received epirubicin and cisplatin. Survival, however, was short (mean 15 weeks). All patients died with symptoms of bleeding, showing clinical and laboratory signs of DIC.

Conclusions: Based on our experience, infusional 5FU is an effective regimen with negligible myelosuppression; thus, it may be a good choice as initial therapy for this group of patients. The response induced by protracted 5FU was usually short and lasted for a few weeks only. Therefore, once DIC symptoms are controlled, the addition of newer cytotoxic drugs may be necessary to consolidate the remission.







[1] DIC = disseminated intravascular coagulation

[2] 5FU = 5-fluorouracil





 

March 2002
Konstantin Lavrenkov, MD, PhD, Sofia Man, MD, David B. Geffen, MD and Yoram Cohen, MD

Background: Recent years have brought significant progress to the development of hormonal therapies for the treatment of breast cancer. Several new agents have been approved for the treatment of breast cancer in the metastatic setting, among which is the new non-steroidal aromatase inhibitor, anastrozole, introduced for clinical use in Israel in March 1997.

Objectives: To evaluate the response rate and survival duration of patients treated with anastrozole for metastatic breast cancer, who had previously received at least one line of hormonal therapy.

Methods: Anastrozole was administered to 37 patients with metastatic breast cancer. The median age was 64 years. Estrogen receptor was positive in 20 patients, negative in 10 and unknown in 7. All patients were previously treated with tamoxifen in the adjuvant setting or as first-line hormonal therapy for metastatic disease. Anastrozole was given orally, 1 mg/day. Response was evaluated 2 months after the initiation of treatment and reevaluated every 2 months. Therapy was given until disease progression. Ten ER[1]-negative patients were excluded from the final analysis.

Results: Twenty-seven patients were eligible for response and toxicity analysis. The median follow-up was 20 months. One patient (3.7%) achieved complete response and remains free of disease 28 months after start of therapy. No partial responses were seen. Twenty patients (74%) had stable disease. Two year actuarial survival was 57%. Median survival was 26.5 months after starting therapy and median progression free survival was 11 months. The toxicity was mild: one patient (3.7%) complained of weight gain and one patient (3.7%) had mild fatigue.

Conclusion: Although the response rate was low, hormonal therapy with anastrozole seems to be beneficial in terms of disease stabilization, freedom from progression, and overall survival without serious toxicity.  






[1] ER = estrogen receptor


November 2000
Samuel Ariad, MD, Micha Barchana, MD, Aviel Yukelson, BSc and David. B Geffen MD
 Background: Exposure to asbestos is the main established cause of mesothelioma; the incidence of this tumor is thus often interpreted as an index of past exposure. Asbestos has been widely used in Israel in industry and building, exposing certain population groups to the risk of developing mesothelioma.

Objectives: To analyze the incidence of mesothelioma in Israel during the years 1960-96, and to project its trend for the following years.

Methods: We conducted a population-based study of the incidence of mesothelioma reported to the Israel Cancer Registry during 1960-96. Time trends were analyzed from data on the annual import of asbestos to Israel, which may indicate the magnitude of past exposure. Based on these findings, trends in the incidence of mesothelioma in Israel were projected for the subsequent years.

Results: A total of 327 cases of mesothelioma were reported to the Israel Cancer Registry during the study period. The incidence in Jews was higher than in Arabs (age-standardized incidence rate 2.64 vs. 1.35 per million/year, respectively). Among the Jewish population, Israeli-born males and males born in Europe and America showed the highest incidence (ASR 4.23 and 4.15 per million/year, respectively). Israeli-born males were 20 years younger than Jewish males born elsewhere. The incidence was twice as high among males than females and increased sevenfold from its nadir (1.17 per million/year) in 1978--80 to its peak (8.5 per million/year) in 1993-96. During a similar period the incidence among females increased from 0.33 to 2.56 per million/year. The incidence in both sexes does not appear to level off. The large wave of immigration from the former Soviet Union that began in 1989 only partly accounts for the increased incidence in 1993-96. The time trend in the incidence of mesothelioma in both sexes parallels the use of asbestos in Israel, which peaked in the years 1976-78.

Conclusions: The incidence of mesothelioma in Israel has increased sharply in recent years, unrelated to a wave of immigration from East Europe, and is predicted to continue to rise for another 10-15 years.

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