Israel Medical Association Journal

Although the free radical theory of aging is widely accepted among scientists, the possibility of using antioxidants to delay the aging processes seems to encounter considerable skeptism among clinicians. This may be, at least in part, due to lack of knowledge about the basic chemistry and biological behavior of oxidative stress, antioxidants, and the complex interactions between them. However, one cannot ignore the explosive growth of information concerning the mechanisms underlying the processes of aging, their consequences, and the use of antioxidants in suppressing such effects. In order to provide patients with the most accurate information regarding the use of antioxidant supplementation in their diet, it is important to obtain basic data regarding oxidative stress and antioxidants. This article explores the role of oxidative stress in the aging phenomena, recent evidence supporting supplementation of antioxidants for aged people,  the ability of antioxidants to prevent or retard cancer and atherosclerosis (the major causes of mortality in the aged population), and the ability of antioxidant supplementation to delay age-dependent deterioration of cognitive function. Based on the data presented, we conclude that current knowledge provides insufficient and inconclusive support for antioxidant supplementation as a means of delaying aging processes, despite the encouraging results obtained in many studies.

Between 1990 and 2001, altogether 28 new anticancer drugs were approved for use in Israel. The new agents include cytotoxic drugs, biologic compounds, and hormone therapies. Among the cytotoxic agents introduced, the taxanes, vinorelbine, gemcitabine, irinotecan, topotecan and temozolomide, represent important new drugs active in a range of solid malignancies including lung, breast, ovarian, bladder, pancreatic, and colon cancer as well as brain tumors. Epirubicin, idarubicin, and liposomal doxorubicin offer less toxic and in some instances more effective alternatives to older anthracylines for leukemia, breast cancer, ovarian cancer and other diseases. New oral agents are offering a chance for disease palliation without the need for burdensome intravenous access. Rituximab and trastuzumab have introduced monoclonal antibody therapy to the clinic, substantially improving the treatment of patients with lymphoma and breast cancer, respectively. The first tyrosine kinase inhibitor, a molecularly targeted therapy, imatinib, was approved for use in chronic myeloid leukemia and has also shown remarkable activity in gastrointestinal stromal tumors. A variety of aromatase inhibitors have provided less toxic and more effective hormone therapy for the treatment of breast cancer. The challenge for clinicians is to optimize the use of the new available agents for their patients' benefit, and the challenge for health policy-makers in Israel is to integrate the new anticancer pharmaceuticals into the basic health benefits package mandated for all citizens.

Background: Genes that confer mild or moderate susceptibility to breast cancer may be involved in the pathogenesis of sporadic breast cancer, modifying the phenotypic expression of mutant BRCA1/BRCA2 alleles. An attractive candidate is the insulin-like growth factor I, a known mitogen to mammary ductal cells in vivo and in vitro, whose serum levels were reportedly elevated in breast cancer patients.

Objective: To evaluate the contribution of the IGF-1 gene polymorphism to breast cancer risk by genotyping for a polymorphic allele size in breast cancer patients and controls.

Methods: We analyzed allele size distribution of the polymorphic CA repeat upstream of the IGF-I gene in 412 Israeli Jewish women: 268 women with breast cancer (212-sporadic and 56 carriers of either a BRCA1:or BRCA2 mutation), and 144 controls. Genotyping was accomplished by radioactive polymerase chain reaction of the relevant genomic region and size fractionation on polyacrylamide gels with subsequent auloradiography,

Results: Among women with breast cancer, with or without BRCA germline mutations, 196 and 198 basepair alleles were present in 4.7% (25/536 alleles), compared with 9% (26/288) controls (P = 0.02). This difference was more pronounced and significant in the non-Ashkenazi population. Conversely, the smaller size allele (176 bp) was present in the breast cancer group only {3/536, 0.6%).

Conclusions: The IGF-I polymorphism may serve as a marker for breast cancer risk in the general Jewish population, in particular non-Ashkenazi Jews, but extension and confirmation of these preliminary data are needed.
 

Background: The treatment of patients with recurrent ovarian carcinoma after failure of first and second-line chemotherapy is still debated. Chemical agents used for third and fourth-line therapy usually yield poor results with severe toxic side effects.

Objective: To summarize our experience with goserelin in the treatment of patients with recurrent ovarian cancer.

Methods: From September 1996 to June 1999 we administered goserelin, 3.6 mg subcutaneously every 4 weeks, to 15 patients with advanced and recurrent epithelial ovarian cancer (median age 59.0, median performance status 3.0).

Results: Seven of 15 eligible patients relapsed after platinum-based chemotherapy (3 of them also received paclitaxel and another 2 received tamoxifen). Four patients relapsed after carboplatin and paclitaxel, one of whom was treated with topotecan thereafter. Two patients relapsed after single-agent paclitaxel. Two patients with advanced disease and poor performance status without previous treatment received only goserelin. There was one complete response (6.7%) and 1 partial response (6.7%) lasting 8 and 14 months respectively (overall response rate 13.4%). In addition, the disease stabilized in three patients (20%) for a median of 7.5 months. In 10 patients the disease progressed. There was no significant toxicity. Median survival of all patients was 5.8 months.

Conclusion: Goserelin was helpful in one-third of our patients with advanced and refractory ovarian cancer. It is an easy and non-toxic option for treating very ill or previously heavily treated patients.
 

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.  

Background: The importance of health promotion and disease prevention in health policy and clinical practice is widely accepted in many countries. However, a large number of medical schools do not dedicate a significant part of their curriculum to these aspects. In Israel, there are no reports on the training of the future physician towards his or her role as health promoter in general, or in the areas of cardiovascular and cancer diseases specifically.

Objectives: To examine the preparation of Israel medical students for the role of health promoter in cancer and cardiovascular diseases.

Methods: The study was carried out over 2 years in two of the four medical schools in Israel: the Sackler Faculty of Medicine at Tel Aviv University and the Faculty of Health Sciences at Ben Gurion University in Beer Sheva. The students (n=172, 70% response rate) were surveyed during 1999-2000 by means of a questionnaire, which included assessment of their training towards the role of health promoter, their clinical experiences and exposure to patients at different stages of illnesses at various medical sites, and the specific skills and relevant knowledge they acquired.

Results: Most of the students’ learning experiences occurred in hospitals with patients at the treatment stage and little time was dedicated to prevention, especially in the community. They demonstrated better knowledge, skills and satisfaction with their learning experiences in CVD than in cancer; and reported having insufficient exposure to several common cancer diseases and lacking examining skills for early detection of cancer. The students in Beer Sheva had significantly more interaction with patients at different stages of CVD and acquired more examination skills than the Tel Aviv students.

Conclusions: A change in the curriculum is urgently needed: namely training medical students in community settings and preparing them to promote the well-being of their patients, including prevention. Attention should be given to launching new learning modes in the pre-clinical and clinical curriculum. We propose that: a) pre-clinical courses include prevention techniques in CVD and cancer, problems of cancer patients, and some examining skills; and b) the clinical phase should integrate oncology concepts and total cancer and CVD care into existing clerkships in the hospitals and in the community.