Fikri Icli

Severe vascular toxicity associated with cisplatin-based chemotherapy.

A 19‐year‐old man with a germ cell tumor who experienced hypertension, acute myocardial infarction, and cerebrovascular accident (CVA) associated with hypomag‐nesemia as late complications of cisplatin‐based chemotherapy is presented, and previously reported cases in the literature are reviewed. Different physiopathologic mechanisms are hypothesized for early and late vascular complications of cisplatin.

Diet and stomach cancer incidence : a case-control study in Turkey

A case‐control study of diet and stomach cancer was conducted in Ankara, Turkey, between December 1987 and March 1988. One hundred patients with adenocarcinoma of the stomach were matched with 100 control subjects according to age, sex, and residential area. A dietary questionnaire was administered to all subjects by one of the authors. Gastric cancer patients consumed less fresh fruit and yellow‐green vegetables (P < 0.0001) and meats (P < 0.001), and more salted food (P < 0.001), condiments (P < 0.0001), and salt (P < 0.001) compared with the control group. Twenty‐four percent of the gastric cancer patients and 4% of the controls had no refrigerator (P < 0.0001). There was no difference between the two groups with regard to the consumption of starches, fried foods, cereals, milk, dairy products, tea, alcohol, and tobacco. Stomach cancer patients brushed their teeth less frequently (P < 0.0001) and had more deficient teeth (P < 0.0001) compared with the control group.

A Randomized Phase III Trial of Etoposide, Epirubicin, and Cisplatin Versus 5-Fluorouracil, Epirubicin, and Cisplatin in the Treatment of Patients with Advanced Gastric Carcinoma

Gastric carcinoma is a substantial health problem in Turkey, and the majority of patients present with inoperable disease. The aim of this randomized trial was to assess the activity of 5‐fluorouracil versus etoposide when combined with epirubicin plus cisplatin in patients with advanced gastric carcinoma (AGC).

Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group

Our objective was to determine whether oral etoposide and cisplatin combination (EoP) is superior to paclitaxel in the treatment of advanced breast cancer (ABC) patients pretreated with anthracyclines. From December 1997 to August 2003, 201 patients were randomised, 100 to EoP and 101 to paclitaxel arms. Four patients in each arm were ineligible. The doses of etoposide and cisplatin were 50 mg p.o. twice a day for 7 days and 70 mg m−2 intravenously (i.v.) on day 1, respectively, and it was 175 mg m−2 on day 1 for paclitaxel. Both treatments were repeated every 3 weeks. A median of four cycles of study treatment was given in both arms. The response rate obtained in the EoP arm was significantly higher (36.3 vs 22.2%; P=0.038). Median response duration was longer for the EoP arm (7 vs 4 months) (P=0.132). Also, time to progression was significantly in favour of the EoP arm (5.5 vs 3.9 months; P=0.003). Median overall survival was again significantly longer in the EoP arm (14 vs 9.5 months; P=0.039). Toxicity profile of both groups was similar. Two patients in each arm were lost due to febrile neutropenia. The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines.

The role of granulocyte‐macrophage‐colony stimulating factor, cortisol, and melatonin in the regulation of the circadian rhythms of peripheral blood cells in healthy volunteers and patients with breast cancer

Abstract: The circulating blood cells show highly reproducible circadian rhythms. However, the factors that regulate these rhythms are not well understood. In the current study, we examined the diurnal variations of peripheral blood cells (white blood cells, neutrophils, lymphocytes), granulocyte‐macrophage‐colony stimulating factor (GM‐CSF), and melatonin levels, and considered the role of melatonin on these rhythms in healthy volunteers and in patients with early breast cancer. Fourteen premenopausal patients with early stage breast cancer (T2, N1 tumors) and 10 premenopausal healthy volunteers were included in the study. Blood samples were taken every 4 hr for a period of 24 hr. Peripheral blood cells were counted by automated analyser and also from peripheral blood films. GM‐CSF levels were measured by ELISA and melatonin levels by radioimmunoassay (RIA). Serum melatonin, cortisol, and GM‐CSF levels, and peripheral blood cell counts showed significant circadian rhythms in healthy volunteers. Except for GM‐CSF, these circadian rhythms were found not to be suppressed in early breast cancer patients. While there were significant correlations of serum GM‐CSF and cortisol levels with peripheral blood cell counts in healthy volunteers, only lymphocyte counts were found to be significantly correlated with serum GM‐CSF and cortisol levels in patients with breast cancer. Serum melatonin levels were found to be significantly correlated with lymphocyte counts in both groups. Our results suggest that peripheral blood cells show significant circadian rhythms in both healthy volunteers and in patients with stage II (T2, N1) breast cancer, and GM‐CSF, cortisol, and melatonin may have a role in the regulation of peripheral blood cell counts.

Daily variations of plasma malondialdehyde levels in patients with early breast cancer

In this study, we aimed to investigate the diurnal variations of malondialdehyde (MDA), in patients with early breast cancer. Ten consecutive premenopausal patients with early stage breast cancer and 10 healthy volunteers were included. Blood samples were taken every 4h for a period of 24h. The peripheral blood cells were counted and the plasma MDA levels measured as an indicator of lipid peroxidation. The daily average MDA levels of the patients were significantly higher than that of the controls (2.7+/-0.2 micromol/ml versus 2.2+/-0.2 micro mol/ml, P=0.044, respectively). The plasma MDA levels of the patients showed significant diurnal variations with the highest levels at 20:00 h and the lowest levels at 04:00 h. In the control group, the plasma MDA levels had no statistically significant diurnal variations. However, the MDA levels at 12:00 and 16:00 h were significantly higher than the levels at 04:00 h. The MDA levels of the patients group were significantly correlated with WBC and neutrophils with a phase difference of 12h (rho=0.341, P=0.012 and rho=0.288, P=0.035, respectively). Though there were weak correlations between the MDA levels and WBC and neutrophils in the control group (rho=0.215, P=0.127 and rho=0.249, P=0.076, respectively), the phase difference was 8h. In conclusion, the current cross-sectional study suggests that the phase differences in daily variations of lipid peroxidation may play a role in carcinogenesis.

The effect of two different doses of oral clodronate on pain in patients with bone metastases

The aim of this study was to evaluate the efficacy of low dose oral clodronate in palliation of pain arising from bone metastases (BM) and to determine the optimal oral clodronate dose which inhibits osteolysis caused by tumor. Fifty patients with bone pain caused by BM were included in this study. All were receiving antitumor chemotherapy or hormonal therapy. The patients were randomized into three groups according to the dose of clodronate. Groups A and B were given 800 mg/d and 1600 mg/d of oral clodronate respectively for 3 months. Group C was the control group. The effect of clodronate in pain palliation was evaluated with pain score, performance status, and changes in analgesic use. The effect on osteolysis was examined with urinary calcium, hydroxyproline (OHP) and serum cross-linked carboxyterminal telopeptide region of type I collagen (ICTP) levels. Group A contained 16 patients, and groups B and C contained 17 patients each. After 3 months use of oral clodronate, significant decrease in the pain score of groups A and B was noted when, compared to group C (P=0.024 andP=0.007, respectively) The analgesic use of 11 patients in group A (69%) and 8 patients in group B (47%) was decreased, but only the decrease in group A was statistically significant (P=0.038). Pain score increased in 5 patients in group C (29%), and 3 patients in groups A (19%) and B (18%) each. Urinary calcium, OHP and serum ICTP levels increased in group C and decreased in groups A and B, but only the decrease of urinary calcium levels of group B was significant (P=0.003). In conclusion, low dose (800 mg/d) oral clodronate seems to be as effective as standard dose (1600 mg/d) in palliation of bone pain secondary to BM.

Prognostic significance of flow cytometric DNA analysis in patients with malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) due to environmental exposure to asbestos and erionite is a relatively common cancer in Turkey. In this study, we investigated the value of flow cytometric (FCM) DNA analysis and other prognostic factors such as age and etiologic factor in the patients with MPM, treated with surgery+/-combination chemotherapy+/-radiotherapy. A total of 40 patients with a median age of 50 (range 30-68) were included in the study. Twenty-nine patients had asbestos exposure in etiology, while 11 had fibrous zeolite (erionite). Paraffin-embedded tumor specimens were studied by FCM for DNA analysis. Twelve patients (30%) had aneuploid tumors and 28 (70%) had diploid ones. Mean S-phase fraction (SPF; %) was 9.1+/-1.1 and proliferation index (PI, SPF+G2/M phase; %) was 11.3+/-0.9. While the median overall survival (OS) was 10+/-2 months (6-14; 95% CI), 1-year survival rate was 45.2%. Only PI was found to be statistically significant for OS in univariate analysis (P=0.013). PI was also found to be an independent prognostic factor for all patients (P=0.035). Aneuploidy was significantly higher in erionite group compared with asbestos group. Male predominance and poor survival were also prominent in erionite group, though not statistically significant. In conclusion, PI is an independent prognostic factor for patients with MPM and the biologic features of the disease may show differences with respect to different etiologies.

Two dose levels of ifosfamide in malignant mesothelioma

Thirty-one consecutive patients with histologically proven and symptomatic malignant mesothelioma were treated with two dose levels of ifosfamide. The first group of 15 patients were given 2.3 g/m2/day for 5 days (group A) and the following 16 patients were treated with 1.2 g/m2/day for 5 days of ifosfamide (group B). Treatment cycles were repeated every 3 weeks. While the partial response rate (PR) in group A was 38.5%, it was only 6.25% in group B (P > 0.05). The 95% confidence interval for the difference in PR rates was 3.3-61.2% > The overall survival (OAS) of groups A and B were similar (8 months and 9 months, respectively). Higher Grade 3-4 myelotoxicity was observed in group A when compared to group B (30.8% vs. 18.7%; P > 0.05). In conclusion, a favourable response rate could be achieved in malignant mesothelioma with high dose ifosfamide at the cost of increased toxicity.

Squamous cell carcinoma of the larynx metastasized to the ampulla of vater. Report of a case

Metastasis to the ampulla of Vater from squamous cell carcinoma of the larynx has not been reported previously. In a 71-year-old Turkish patient with squamous cell carcinoma of the larynx a polypoid tumor was observed in the ampulla of Vater. Histopathological examination revealed squamous cell carcinoma compatible with metastasis from laryngeal cancer.