Electronic Library of Scientific Literature


Volume 46 / No. 2 / 1999


About the antiemetic effectivity of granisetron in chemotherapy-induced acute emesis: A comparison of results with intravenous and oral dosing

O. Lehoczky

Gynecologic Oncology Department, National Institute of Oncology, 1122 Budapest, Hungary

The paper is devoted to review literature data on intravenous and oral antiemetic effectivity of granisetron (GRAN) a selective 5HT3 antagonist and to determine the optimal dose for the prophylaxis of chemotherapy-induced acute emesis. The drug was put on the market in the injectable form in 1994 and in the oral form in 1995, so a sufficient number of reports have been published for the evaluation.
According to the summarized data on 6095 patients treated with intravenous GRAN, on average 66% antiemetic complete response (CR) rate was reached (i.e. no vomiting in the first 24 hours of chemotherapy). Best results were observed with the dose of 40 microg/kg intravenous GRAN, on average 70% CR (range 47-93%) were achieved in 4182 of the 6095 patients with this dose. In 942 patients treated with the mostly applied oral dose of GRAN (1 mg twice daily), on average 61% CR (range 52-82%) were reported. Side effects were weak and transient, mostly headache and constipation were observed. Headache appeared in 13% with the use of 40 microg/kg intravenous dose GRAN and in 18% with 1 mg oral dose twice daily. Constipation was observed in 5.3% and 17% with the injection and oral dose, respectively.

Key words: Granisetron, chemotherapy-induced emesis, antiemetic.
NEOPLASMA, 46, 2, 1999, pp. 73-79

FASAY: a simple functional assay in yeast for identification of p53 mutation in tumors

J. Šmardová

Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic

Alteration of the p53 tumor suppressor gene is the most common genetic defect known to occur in human tumors. Germ-line p53 mutations significantly increase the risk of developing diverse malignancies. FASAY is a simple functional assay for germ-line and somatic mutations in the p53 gene altering the transactivation capability of the p53 protein. The method was succesfully used for mutation analysis of p53 in various cell lines, somatic tumor cells and blood cells. In addition, FASAY was also found effective as a tool for basic research of binding of mutant p53 proteins to promoters of different p53 target genes.

Key words: p53, mutation, transactivation, FASAY.
NEOPLASMA, 46, 2, 1999, pp. 80-88

Kojic acid - a new leading molecule for a preparation of compounds with an anti-neoplastic potential

L. Novotný, P. Rauko, M. Abdel-Hamid, A. Váchalková

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, 13110 Safat, Kuwait;
Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovak Republic

Kojic acid as a molecule of natural origin may serve as template for the synthesis of new biologically active compounds. The synthetic KA (pyranone) derivatives possess various kinds of biological activities which are related by their similarity to flavonoids. The most important property is the antifungal and antineoplastic activity and capability of chelating metals. It is shown that the antineoplastic activity of kojic acid derivatives is based on various mechanisms of action on different levels of cellular metabolism and functions what makes this compound interesting for future investigation as cytotoxic agent.

Key words: Kojic acid, kojic acid derivatives, antifungal activity, antileukemic activity.
NEOPLASMA, 46, 2, 1999, pp. 89-92

Symptom pattern and diagnostic work-up of malignancy at first symptom presentation as related to level of care
A retrospective study from the primary health care centre area of Kungsbacka, Sweden

J. Månsson, C. Björkelund, R. Hultborn

Health Centre of Kungsbacka, 434 30 Kungsbacka, Sweden;
Department of Primary Health Care, Göteborg, University Göteborg, Sweden;
Department of Oncology, Göteborg University, Göteborg, Sweden

This retrospective study was aimed to characterize the diagnostic process of cancer with respect to level of care, initial symptoms, and diagnostic procedures. It was based on analysis of medical records of all subjects with colorectal, pulmonary, breast or prostate cancer, reported to the Swedish Cancer Registry during defined periods of time in the community of Kungsbacka with about 46 500 inhabitants. Initial symptoms, diagnostic procedures, outcome of diagnostic procedures, level of care, and doctor's delay were analyzed.
Most patients (62-73% for the different cancers studied) first visited a general practitioner for the symptoms which lead to the diagnosis of cancer. The most common initial symptom for colorectal cancer was defecation abnormality, for breast cancer a palpable mass in the breast, for pulmonary cancer cough, and for prostate cancer symptoms of prostatism. There was no difference in doctor's delay between general practitioners and other physicians. Nonspecific blood laboratory tests made little contribution to the diagnosis of cancer.
The results indicate that most cancers of the types studied are diagnosed in primary health care and that it is possible to improve the identification of the few malignant cases among the "noise" of benign diseases, both with respect to accuracy and cost-effectiveness. It seems that focused investigations such as fecal occult blood tests and rectoscopy should be more frequently used in patients with gastrointestinal symptoms.

Key words: Cancer, diagnosis, doctor's delay, level of care, primary health care.
NEOPLASMA, 46, 2, 1999, pp. 93-99

Copper, zinc and superoxide dismutase in precancerous, benign diseases and gastric, colorectal and breast cancer

T. Magálová, V. Bella, A. Brtková, I. Beòo, M. Kudláèková, K. Volkovová

Research Institute of Nutrition, 833 37 Bratislava, Slovak Republic;
National Cancer Institute, Bratislava, Slovak Republic

The aim of the present study was to assess serum levels of copper and zinc levels and erythrocytes Cu,Zn-SOD activity and to determine probable changes in gastric and colorectal precancerous diseases, benign breast diseases, gastric, colorectal and breast cancer.
The study included 165 subjects with cancer, 348 subjects with precancerous (atrophic gastritis, gastric adenoma, colon adenoma, rectal adenoma) and/or benign diseases (weak dysplasia, severe dysplasia, fibroadenoma, cystic disease) and 161 randomly selected healthy controls.
Our results suggest that while in gastric and colorectal cancer there were mostly increased copper levels, in breast cancer they were not changed. Zinc levels were weakly decreased in atrophic gastritis, gastric adenoma and breast cancer.
There was a strong positive correlation between zinc levels and SOD activity in fibroadenoma and a weak positive correlation in colorectal adenoma and colorectal cancer without any correlation between SOD activity and copper in these groups. In gastric precancerous disease there was a positive correlation between SOD and copper.
The results of this study suggest that serum trace element levels and activity of related enzymes might be different in various neoplastic processes. This variation in neoplastic processes might be influenced by other factors that have to be considered in complex relationships between the whole body and neoplastic cells.

Key words: Superoxide dismutase, copper, zinc, gastric, colorectal and breast cancer, benign diseases, precancerous diseases.
NEOPLASMA, 46, 2, 1999, pp. 100-104

Inhibitory effect of Trianthema portulacastrum L. diethylnitroso­amine-induced phenobarbital promoted hepatocarcinogenesis

S. Bhattacharya, M. Chatterjee

Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, Calcutta 700 006, India

The chloroform extract (active components from the exotic weed Trianthema portulacastrum L. of Aizoaceae, showed remarkable effect in the reduction of DENA-induced rat hepatocarcinogenesis. Hepatocarcinogenesis was induced in male Sprague-Dawley rats by a single intraperitonial injection of diethylnitrosoamine (DENA) at a dose of 200 mg/kg body weight. Chloroform extract of T. portulacastrum at a dose of 100 mg/kg/body wt. to the basal medium/per animal once daily was administered following DENA injection. Morphometric evaluation revealed that the fraction reduced the incidence, numerical preponderance, multiplicity and size distribution of visible pre-neoplastic nodules. Further focal lesions showed a reduction of altered liver cell foci/cm2 and a reduction of average focal area. A decrease in the percentage of liver parenchyma occupied by foci all seem to suggest the anticarcinogenic potential of Trianthema portulacastrum in DENA-induced rat hepatocarcinogenesis.

Key words: Diethylnitrosoamine, pre-neoplastic nodules, hepatocarcinogenesis.

NEOPLASMA, 46, 2, 1999, pp. 105-111

Estradiol receptor and prognostic parameters of human breast cancer

M. Görlich, B. Jandrig

Max Delbrück Center of Molecular Medicine, 13 092 Berlin, FRG

Estradiol receptors are regarded to predict a likely success of hormonal therapeutic efforts and the prognosis of breast cancer patients. But today its prognostic importance is controversial, discussed as either reflecting intrinsic property of the tumor tissue or better therapeutic accessibility of receptor positive tumors. Moreover, the most important clinical prognosticators - tumor size and axillary lymph node involvement do not seem to be related to the estradiol receptor status.
In our investigation, the length of disease free interval is similar in estradiol receptor positive and negative patients and in all sites of distant metastases, but it is significantly reduced if more than 4 axillary lymph nodes are involved.
Post recurrence survival is significantly longer in estradiol receptor positive than negative patients and also in patients treated by tamoxifen containing therapies. Its length is independent of the number of axillary lymph node metastases and the type of distant metastases, with a tendency to be longer in estradiol receptor positive than negative patients.
In addition, the overall survival is longer for estradiol receptor positive than negative patients and becomes reduced with more than 4 axillary lymph node metastases. Frequency of deaths in estradiol receptor positive patients is half that of negative subjects. Furthermore, the length of overall survival is independent on the type of distant metastases, with tendency to be longer in estradiol receptor positive than negative patients. Longest overall survival could be observed for estradiol receptor positive patients who got therapy regimens containing tamoxifen.
The weak prognostic advantages of estradiol receptor positive patients are interpreted by estradiol receptors as intrinsic parameters of breast cancer tissue characterizing more its biological behavior than therapeutic accessibility.

Key words: Breast cancer, estradiol receptor, prognosis, metastasis, therapy regimen.
NEOPLASMA, 46, 2, 1999, pp. 112-116

Enhanced activity of estramustine, vinblastine, etoposide, and suramin in prostate carcinoma

I.N. Arah, S.C. Dixon, J. Horti, W.D. Figg

Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institute of Health, Bethesda, Maryland 20 892, USA

Following hormonal therapy, few treatment regimens have activity in metastatic prostate cancer. Cytotoxic agents have minimal activity in this disease. However, combinations of cytotoxic agents may be beneficial. The activity of estramustine, vinblastine, etoposide, and suramin on cell growth was evaluated. Prostate specific antigen (PSA) is routinely used as a surrogate marker for disease progression. Many pharmacological agents alter PSA levels independently of their effect on tumor growth, the effect of these agents on PSA secretion was determined. Each agent was evaluated alone and in combination with the other drugs in two prostate cancer cell lines. In LNCaP cells, estramustine and suramin were cytostatic, while vinblastine and etoposide were cytotoxic. Estramustine down-regulated etoposide PSA secretion, while suramin had no effect. The effects of etoposide and vinblastine on PSA secretion were not evaluable. In PC-3 cells, only etoposide was cytotoxic. Tandem combinations were more cytotoxic than single agents in both cell lines. The addition of a third agent to the tandem combination produced less cytotoxicity. In our hands, the best combinations were estramustine/vinblastine, suramin/vinblastine, and suramin/etoposide. These combinations yielded 20-60% higher cytotoxicity than any of the drugs alone.

Key words: Hormone refractory prostate cancer, prostate specific antigen, chemotherapy.
NEOPLASMA, 46, 2, 1999, pp. 117-123

The surgical treatment of adrenal gland tumors - incidentaloma

K. Kolomecki, L. Pomorski, K. Kuzdak, J. Narebski, R. Wichman

Department of Endocrinological and General Surgery, Medical University of Lodz, Copernicus Hospital, 93 - 513 Lodz, Poland

Analysis of 32 patients operated on because of accidentally discovered adrenal tumors "incidentaloma" is presented. In 12 of them there was subclinical hormonal activity, in 9 of them tumors turned out to be pheochromocytoma and 3 of them were cortex adenoma. There were 20 hormonally inactive tumors, in 5 of them there were malignant lesions (4 of the cortex and 1 of the medulla). For evaluation of hormonal activity of adrenal tumors evaluation of chromogranin A and cortisol serum blood level or urine free cortisol level is recommended. For precise localization of the tumor beside USG also CT examination is of use. According to the high percentage of malignant lesions in "incidentaloma" type tumors, surgery treatment without delay is recommended. BAC or DHES in blood serum examinations were not found helpful in preoperative evaluating the lesions as benign or malignant.In case of preoperatively found subclinical hormonal hyperactivity of medulla pharmacological treatment with alpha and beta blockers in surgery preparation is recommended. Lateral extraperitoneal access for adrenalectomy is considered safe and provides good operational view. Laparoscopic procedure because of high percentage of malignant lesions in this group of patients is not justified.

Key words: Incidentaloma, adrenalectomy, adrenal gland, tumor.
NEOPLASMA, 46, 2, 1999, pp. 124-127

Primary cancer of the fallopian tube with transitional differentiation Clinical and pathological assessment of 6 cases

J.K. Rabczyñski, A.T. Kochman

Department of Pathological Anatomy, Medical University of Wroclaw, 50-368 Wroclaw, Poland

To establish prognosis, histologic appearance and p53 and c-erbB-2 expression in cancer tissue, six cases of primary transitional cancer of the fallopian tube were analyzed. Among 45 patients with the primary cancer of the fallopian tube diagnosed between 1992 and 1997, we found six cases diagnosed previously as solid (undifferentiated) cancer of the tube. p53 protein and c-erbB-2 oncoprotein expression were examined using an avidin-biothinyl-peroxydase complex method. The accumulation of p-53 protein and c-erbB-2 oncoprotein were used as prognostic marker of the transitional cancer of the tube. According to histologic picture all patients were diagnosed for primary cancer of the tube with transitional differentiation. In 4 cases strong positive and in 2 cases moderate positive reaction with antibody against p53 protein was seen for p53 protein. No positive expression of c-erbB-2 oncoprotein in membrane of cancer cells in our cases was detected. Presence p-53 protein in all our 6 cases deny the usefulness of the p53 protein as prognostic marker in primary cancer of the fallopian tube. Lack of expression of c-erbB-2 oncoprotein in membrane of cancer cells is significantly contributed to better prognosis in cases with primary cancer of the tube with transitional differentiation.

Key words: Fallopian tube, p-53 protein, c-erbB-2 oncoprotein, cancer with transitional differentiation.
NEOPLASMA, 46, 2, 1999, pp. 128-131

The role of stable disease in objective response assessment and its impact on survival in advanced colorectal cancer: Is "stable disease" a homogenous response category?

I. Popov, S. Jeliæ, D. Radosavljeviæ, Z. Nikoliæ-Tomaševiæ

Institute of Oncology and Radiology of Serbia, 11 000 Belgrade, Yugoslavia

Stable disease is a category which is not included in the evaluation of the overall treatment response rate. In many studies with a response rate below 20%, chemotherapy almost doubles the survival of patients. In the most chemotherapy trials with advanced colorectal cancer patients, about 30-50% had stable disease. Despite belonging to the same category of therapy response, some patients with stable disease have achieved symptom improvement, but some have not. The aim of the study was to investigate whether the stabilization of the disease with clinical benefit is associated with benefit in survival.
A total of 99 patients with advanced colorectal cancer were treated with carboplatin (80 mg/m2, day 1-7), 5-FU (750 mg/m2, day 1-5), leucovorin (100 mg/m2, day 1-5) every 4 weeks. After 4 courses, in the case of stable disease (SD), the patients were stratified according to clinical benefit achievement in: Group A - patients with clinical benefit who continued with chemotherapy until 8 cycles or until disease progression; group B - patients without clinical benefit in whom chemotherapy was stopped after 4 cycles. Clinical benefit was a composite of assessment of pain, ECOG performance status, weight and temperature. Clinical benefit required a sustained improvement in at least one parameter without worsening in any other.
Of 97 evaluable patients 48 achieved stable disease. Of 22 pts. with SD clinical benefit performance status improvement was recorded in 17, pain relief in 14, improvement in body weight in 14 and temperature disappearance in 8 pts. Of 26 pts. with SD without clinical benefit, 7 were asymptomatic from beginning of the chemotherapy. No difference was detected in the survival between responders and SD clinical benefit pts. (p = 0.24), but there was significant difference between responders and SD pts. without clinical benefit (p = 0.0004). SD clinical benefit pts. had significant difference in survival in comparison to pts. with progressive disease (p = 5.1 x l0-6).
The results of our study indicate that under category "stable disease" there are two different subpopulations of patients with quite different symptom response to chemotherapy, different time to progression and possible different survival.

Key words: Advanced colorectal cancer, clinical benefit, stable disease, survival.
NEOPLASMA, 46, 2, 1999, pp. 132-139