Hypoxia inducible factor-1 alpha and carbonic anhydrase IX overexpression are associated with poor survival in breast cancer patients.

PURPOSE: Hypoxia is common in many solid tumors such as breast, head-neck, and soft tissue malignancies. Hypoxia causes overexpression of hypoxia inducible factor-1 alpha (HIF-1α) and carbonic anhydrase IX (CA IX) which are associated with unfavorable prognosis in breast cancer. In our study, we evaluated HIF-1α and CA IX expression in patients with breast cancer. METHODS: Between June 1996 and June 2008, 111 women with breast cancer were evaluated. Estrogen receptor (ER) and progesterone receptor (PR) status and Her2/ neu expression were evaluated by immunohistochemical methods. Her-2/neu expression was also assessed by FISH method when needed. Two groups were created: ER and PR positive, Her-2/neu negative (group 1, n=56); and ER and PR negative, Her-2/neu positive (group 2, n=55). HIF-1α and CA IX expressions were investigated in both groups and results were compared. In addition, we investigated the association between HIF-1α and CA IX expressions with stage, grade, lymph node metastasis, tumor size, menopause status and survival. RESULTS: Median patient age in group 1 was 52 years (range 34-77), and in group 2 47 years (range 27-83). HIF-1α expression was detected in 26 (46.4%) of group 1 and in 46 (83.6%) of group 2 patients (p=0.0001). CA IX expression was detected in 25 (46.4%) of group 1 and in 37 (67.3%) of group 2 patients (p7equals;0.0137rpar;. In group 1, median disease free survival (DFS) was 97 months and in group 2 46 months (p=0.0308). In group 1, median overall survival (OS) was 108 months and in group 2 75 months (p=0.0339). CONCLUSION: HIF-1α and CA IX overexpressions are observed more often in ER and PR negative, Her-2/neu positive breast cancer and are associated with poor survival.

Effect of tamoxifen on serum IL-18, vascular endothelial growth factor and nitric oxide activities in breast carcinoma patients.

Vascular endothelial growth factor (VEGF) is a multi-functional cytokine that has been suggested to be a major angiogenic factor in breast cancer. Nitric oxide (NO) is a potent biological molecule that participates in the multi-step process of carcinogenesis. Interleukin (IL)-18 has been shown to have potent anti-tumour effects. In this study, we investigated the effect of tamoxifen therapy on serum VEGF, NO and IL-18 activity in breast cancer patients. Serum levels of VEGF, nitrate + nitrite and IL-18 were measured in 34 postmenopausal breast cancer patients before and 3 months after the tamoxifen therapy. Both serum VEGF and IL-18 levels decreased after tamoxifen therapy (P = 0.051, P < 0.05, respectively). Serum VEGF levels increased in patients with endometrial thickness, while patients without endometrial thickness had a significant reduction in serum VEGF levels after therapy (P < 0.05). Serum nitrate + nitrite levels increased after the therapy, but this was not statistically significant (P > 0.05). A decrease in serum VEGF levels with tamoxifen therapy may be a reflection of reduced angiogenic activity in patients without endometrial thickness. The negative effect of tamoxifen therapy on IL-18, which is known to have a potent antitumour activity, may be related to the decreased tumour growth by induction of NO and reduction of VEGF activity as a feedback mechanism.

No association between serum levels of insulin-like growth factor-I, vascular endothelial growth factor, prolactin and clinicopathological characteristics of breast carcinoma after surgery.

BACKGROUND: Angiogenesis is essential for tumour growth and metastasis. Vascular endothelial growth factor (VEGF) has been suggested as the major angio-genic factor in breast carcinoma. Both insulin-like growth factor-I (IGF-I) and prolactin are involved in the progression of breast cancer at least partly by stimulating angiogenesis. AIM: The aim of the present study was to investigate the association between serum IGF-I, VEGF and prolactin levels and clinicopathological characteristics of breast carcinoma. METHODS: Serum IGF-I, VEGF and prolactin levels were measured in breast cancer patients and controls and these levels were compared with well-known clinicopathological characteristics of breast carcinoma, including tumour size, axillary lymph node and oestrogen/progesterone receptor status, tumour grade and disease stage. RESULTS: Serum prolactin, VEGF and IGF-I levels were found to be similar in breast cancer patients and control subjects (P > 0.05). When the patients were divided into groups according to their tumour size, axillary lymph node status, tumour grade, oestrogen/progesterone receptor status and disease stage, no significant differences in serum prolactin, VEGF and IGF-I levels were found among the groups (P > 0.05). CONCLUSIONS: The present study failed to demonstrate an association between serum levels of VEGF, IGF-I and prolactin and well-known clinicopathological characteristics of breast carcinoma.

Serum hepatocyte growth factor and interleukin-6 levels can distinguish patients with primary or metastatic liver tumors from those with benign liver lesions.

Hepatocyte growth factor (HGF) is a potent stimulator of angiogenesis and cancer metastasis. Interleukin-6 (IL-6) is a pleiotropic cytokine that can act as an autocrine or paracrine growth factor in various tumor cells. In this study, we investigated the role of serum HGF and IL-6 levels to distinguish primary or metastatic liver tumors from benign liver lesions. Serum HGF and IL-6 levels were measured in 64 cancer patients and 12 healthy controls. Patients were divided into 5 groups: Group-1 (n=24): Breast cancer patients in complete remission without any liver lesion, Group-2 (n=8): Breast cancer patients in complete remission with benign liver lesion, Group-3 (n=10): Breast cancer patients with liver metastasis, Group-4 (n=11): Metastatic breast cancer patients without liver metastasis, Group-5 (n=11): Patients with hepatocellular carcinoma. Group-6 (n=12): Healthy controls. Serum HGF levels were found to be higher in group-5 (606.4+/-255.8 pg/ml) than those in group-1 (*305.6+/-42.3 pg/ml), group-2 (*293.9+/-44.8 pg/ml), group-4 (**358.4+/-81.9 pg/ml) and group-6 (*305.8+/-24.9 pg/ml) (*p<0.001, **p<0.05). Patients in group-3 (448.9+/-157.3 pg/ml) had higher serum HGF levels than those in group-1, group-2 and group-6 (p<0.05). Serum IL-6 levels were found to be higher in group-5 (54.9+/-37.4 pg/ml) than those in group-1 (9.7+/-6.4 pg/ml), group-2 (9.5+/-4.8 pg/ml), group-4 (17.6+/-19.6 pg/ml) and group-6 (12.6+/-5.2 pg/ml, p<0.05). Patients in group-3 (32.5+/-36.9 pg/ml) had higher serum IL-6 levels than those in group-1, 2 and group-6, but these were not statistically significant (p>0.05). This study showed that primer and metastatic liver tumors had higher serum HGF and IL-6 levels than other patients and controls. Measurements of these markers in serum may be used to distinguish patients with primer liver tumors or breast cancer patients with liver metastasis from those with benign liver lesions or non-metastatic patients.

Serum levels of interleukin-18 and nitrite+nitrate in renal cell carcinoma patients with different tumor stage and grade.

Interleukin (IL-18) and nitric oxide (NO) are immunoregulatory cytokines that have been suggested to participitate in the multistep process of carcinogenesis. In this study, serum IL-18 and nitrite+nitrate levels (as an index of NO generation) were measured in 26 patients with histologically confirmed renal cell carcinoma (RCC) before surgical procedure and in 8 healthy controls. RCC patients showed significantly higher serum IL-18 levels when compared to the control subjects (p<0.001). Serum IL-18 levels were found to be similar in patients with T1 and T2, T3, T4 tumors (p>0.05). Patients with grade 3 and 4 tumors showed significantly higher serum IL-18 levels when compared to the patients with grade 1 and 2 tumors (p<0.05). No significant difference was found in serum nitrite+nitrate levels between RCC patients and control subjects (p>0.05). Serum nitrite+nitrate levels were lower in patients with grade 3 and 4 tumors than those with grade 1 and 2 tumors, but this was not statistically significant (p=0.063). In conclusion, elevated serum level of IL-18 in RCC patients than in controls and extra-increase of this level in those with high grade tumors may reflect the degree of human defence mechanisms against tumor cells in RCC.

Effect of different neoadjuvant chemotherapy regimens on locally advanced breast cancer.

In this retrospective study, we evaluated the results of 91 locally advanced breast cancer (LABC) patients (30 patients in stage IIIA - 33.0%, 61 patients in stage IIIB - 67.0%) who had been treated with different neoadjuvant chemotherapy regimens. Forty-three (47.3%) patients treated with FAC (5-Fluorouracil, doxorubicin, cyclophosphamide) or CA (cyclophosphamide, doxorubicin), 33 (36.3%) with FEC (5-Fluorouracil, epirubicin, cyclophosphamide) or CE (cyclophosphamide, epirubicin) and 15 (16.5%) with CMF (cyclophosphamide, methotrexate, 5-Fluorouracil) combination as neoadjuvant setting. Median follow-up duration was 33 (6-116) months in 91 patients. There was no significant difference in the pretreatment characteristics of patients receiving FAC/CA, FEC/CE and CMF including age, disease stage, menopausal and estrogen/progesteron receptor (ER/PR) status (p>0.05). In CMF group, no patient was treated with taxan as adjuvant setting. However, ten patients (30.3%) in FEC/CE group and 21 patients (48.8%) in FAC/CA group were treated with taxans. Overall response rate was lower in CMF group (60.0%), when compared to FEC/CE (81.9%) and FAC/CA (91.0%) groups (p<0.05). Median overall survival (OS) and diseases free survival (DFS) were similar in three groups; 28.0 months (range: 14.8-41.1) and 12.0 months (range: 5.3-18.6) in CMF, 45.0 months (range: 16.8-73.1) and 23.0 months (range: 0.0-48.6) in FEC/CE, 46.0 months (range: 41.1-50.8) and 22.0 months (range: 11.1-32.8) months in FAC/CA groups, respectively (p>0.05). In conclusion, overall response rates were found to be higher in anthracycline-based combinations than CMF, but these regimens had no additional survival advantage over CMF regimen. Long-term effects of these regimens should be investigated in further randomized trials.

High-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous stem cell transplantation in patients with advanced breast cancer: a retrospective evaluation.

This study was conducted to evaluate the efficacy of high-dose thiotepa, melphalan and carboplatin (TMCb) regimen in 27 patients undergoing autologous stem cell transplantation (ASCT) for metastatic breast cancer. A total of 27 patients with stage IV breast cancer underwent ASCT following thiotepa (500 mg/m(2)), melphalan (100 mg/m(2)) and carboplatin (1200-1350 mg/m(2)). Of 27 patients, 17 had refractory relapse, eight had responding relapse, and two had no evidence of disease (NED) at the time of transplant. In all, 11 patients had only bone disease, nine had bone plus visceral disease, three had only visceral disease, and two had locoregional recurrent disease. The median time from diagnosis to transplant was 1081 days (range 180-2341). Staging for evaluation of response was performed 4-6 months after transplantation. Five patients were not evaluable (NE) for response because of NED at transplant (n=2) or early death due to transplant-related complications (n=3) (two of viral pneumonia and one of regimen-related toxicity) occurring at a median of 4 days (range 11-46) post-transplant. One of the two patients who was NED at the time of transplant is still NED on day 760 post-transplant. Seven of 15 refractory (47%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft-tissue disease with at least improvement in bone lesions. Of 27 patients (37%),(10) are alive and progression-free, a median of 582 days (range 410-1380) after treatment, 6/17 (35%) with refractory disease and 4/10 (40%) with responsive disease. The probability of progression-free survival (PFS) for all patients was 0.50. The probabilities of PFS at 2 years for patients with refractory (n=17) and responsive (n=10) disease were 0.42 and 0.60, respectively. PFS at 2 years for the 14 patients who were NED or achieved CR/PR(*) following-HDC was 0.67. PFS at 2 years for patients who did not achieve CR/PR(*) following-DHC was 0.33. These preliminary data suggest that high-dose TMCb followed by autologous stem cell transplantation is an effective regimen for patients with advanced breast cancer and may be comparable to some previously used regimens.

Serum leptin, prolactin and vascular endothelial growth factor (VEGF) levels in patients with breast cancer.

Angiogenesis plays an important role in tumor growth and metastasis in solid tumors. VEGF is an important regulator of tumor angiogenesis. Both leptin and prolactin have also been suggested to have roles in the regulation of angiogenic process. In our study, we measured serum leptin, prolactin and VEGF levels in 30 metastatic, 55 non-metastatic breast cancer patients and 25 control subjects. Serum leptin levels were found to be similar in non-metastatic (38.1+/-19.5 ng/ml), metastatic patients (39.6+/-16.3 ng/ml) and control subjects (35.6+/-13.9 ng/ml) (p>0.05). There was no statistically significant difference between patients with visceral metastasis (44.0+/-16.8 ng/ml) and patients with bone metastasis (35.2+/-15.0 ng/ml) (p>0.05). Serum prolactin levels were found to be similar in non-metastatic (12.2+/-10.7 ng/ml), metastatic patients (11.6+/-8.2 ng/ml) and control subjects (12.3+/-8.1 ng/ml), (p>0.05). Moreover, serum prolactin levels were not different in patients with visceral (11.4+/-8.8 ng/ml) and bone metastasis (11.8+/-8.0 ng/ml), (p>0.05). Metastatic patients had higher serum VEGF levels (249.8+/-154.9 pg/ml), when compared to the non-metastatic patients (138.7+/-59.3 pg/ml) and control subjects (108.4+/-47.7 pg/ml), (p<0.05). There was no difference in serum VEGF levels in non-metastatic patients and control subjects (p>0.05). Patients with visceral metastasis (337.0+/-168.0 pg/ml) had higher serum VEGF levels, when compared to patients with bone metastasis (162.6+71.8 pg/ml), (p<0.05). Serum VEGF activity may be used to evaluate angiogenic and metastatic activity in breast cancer patients. However, serum leptin and prolactin levels does not seem to be related with angiogenic activity and metastasis in breast cancer patients.

Tamoxifen therapy and hepatic steatosis.

Tamoxifen has been used for a long time as a hormonal treatment in breast cancer. Recent studies in pre and postmenopausal women have shown that tamoxifen exhibits favorable effects on the lipid profile. In this study we investigated the effects of tamoxifen on lipid profile and hepatic steatosis. Fifty two (31 postmenopausal and 21 premenopausal) women with breast cancer treated with tamoxifen at a dose of 20 mg daily were included in the study. Serum lipid parameters (total cholesterol, high and low density lipoprotein cholesterol and triglyceride) were measured baseline and at the 6th month of tamoxifen treatment. Upper abdominal ultrasonography was performed before and at the 6th month of therapy for assessment of liver steatosis. We obtained decreased levels of serum total cholesterol after 6 months of tamoxifen treatment (p < 0.05). However, we did not detect any changes in triglyceride and high-density lipoprotein cholesterol levels (p > 0.05). Increased liver steatosis was observed in 22 patients (42.3%) after tamoxifen treatment. We could not detect increase in lipid levels in these patients. There was no significant difference between the lipid levels in the patients with increased liver steatosis and stable or no liver steatosis. Whether hepatic steatosis is dependent on lipid changes in tamoxifen use should be further investigated.

A randomized trial of assessment of efficacy of leukapheresis volumes, 8 liters vs 12 liters.

It is logical to expect that large-volume leukapheresis may be able to collect adequate numbers of PBSC with fewer procedures. To date, there is no agreement on the optimal volume of leukapheresis. Therefore, in this study we compared 8 l volume with 12 l and assessed whether a 50% increase in the blood volume processed would decrease the number of leukaphereses each patient needed to collect > or =2.5 x 10(6) CD34(+) cells/kg in normal mobilizers. PBSC mobilization was done with cyclophosphamide etoposide followed by rhG-CSF in all patients. Forty patients were randomized to undergo 8 l leukaphereses (n = 20 patients) or 12 l leukaphereses (n = 20). The median numbers of leukaphereses required in order to collect > or =2.5 x 10(6) CD34(+) cells/kg in patients processed with 8 l and 12 l were 1 (range 1-5) and 1 (1-4), respectively (P = 0.50). The median number of total nucleated cells (TNC) collected per patient was greater for the 12 l group (7.47 x 10(8)/kg vs 3.90 x 10(8)/kg, P < 0.001), as was the median number of total mononuclear cells (TMNC) (4.26 x 10(8)/kg vs 2.16 x 10(8)/kg, P < 0.001), whereas there was no difference between the two groups for the median number of CD34(+)cells collected per patient (8.94 x 10(6)/kg vs 8.60 x 10(6)/kg, P = 0.85). The TNCs and TMNCs collected per leukapheresis were again greater for the 12 l group (3.64 x 10(8)/kg vs 1.91 x 10(8)/kg, P = 0.001 and 2.17 x 10(8)/kg vs 0.88 x 10(8)/kg, P < 0.001), whereas there was no difference between the two groups for the median number of CD34(+) cells collected per leukapheresis (3.98 x 10(6)/kg vs 3.26 x 10(6)/kg, P = 0.90). This study showed that there is no difference between 8 l and 12 l volumes in regard to collected CD34(+) cells/kg and also the use of a 12 l leukapheresis volume did not decrease the number of leukaphereses performed compared with a 8 l leukapheresis volume. In fact, the use of the larger leukapheresis volume had the disadvantage of adding 60 min to the time the patient was on the machine.

Mobilization of peripheral blood stem cells with chemotherapy and recombinant human granulocyte colony-stimulating factor (rhG-CSF): a randomized evaluation of different doses of rhG-CSF.

To date, no randomized study has compared different doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF) following submyeloablative mobilization chemotherapy. Therefore, we evaluated the effect of different doses of rhG-CSF following mobilization chemotherapy on yields of CD34+ peripheral blood stem cells (PBSC). Fifty patients were randomized to receive 8 (n = 25) versus 16 microg/kg/d (n = 25) of rhG-CSF following mobilization chemotherapy. The median number of CD34+ cells collected after 8 microg/kg/d of rhG-CSF was 2.36 x 10(6)/kg (range, 0.21-7.80), compared with 7.99 (2.76-14.89) after 16 microg/kg/d (P < 0.001). Twenty out of 25 (80%) patients in the low-dose and 23 out of 25 (92%) in the high-dose rhG-CSF arm underwent high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Median days to white blood cell engraftment in patients mobilized with 8 microg/kg and 16 microg/kg of rhG-CSF were 12 (10-20) and 9 (8-11) respectively (P < 0.001). There was no difference between the two groups regarding the other parameters of peritransplant morbidity: days to platelet engraftment (P = 0.10), number of red blood cell (P = 0.56) and platelet transfusions (P = 0.22), days of total parenteral nutrition requirement (P = 0.84), fever (P = 0.93) and antibiotics (P = 0.77), and number of different antibiotics used (P = 0.58). These data showed that higher doses of rhG-CSF following submyeloablative mobilization chemotherapy were associated with a clear dose-response effect based on the collected cell yields. Based on the parameters of peritransplant morbidity, 8 microg/kg/d was as effective as 16 microg/kg/d except for a rapid neutrophil engraftment in the high-dose arm. Therefore, in routine clinical practice, despite some advantage in the use of higher doses of rhG-CSF, lower doses may be used for PBSC collections following chemotherapy-based mobilization regimens in this cost-conscious era.

The clinicopathologic characteristics of colorectal cancer in patients under 50 years of age: experience of an oncology center.

BACKGROUND/AIM: Colorectal cancer is seen mostly among patients older than 50 years of age. An aggressive behavior is a frequently cited as characteristic of colorectal cancer in young patients. The purpose of the present study was to reveal the clinicopathologic characteristics of colorectal cancer among patients under 50 years of age. METHODS: Two hundred and seventy-one patients with colorectal cancer admitted to our oncology center were evaluated, and clinicopathologic findings of the young and old patients were compared. Patient gender, site distribution, tumor stage classification, lymph node involvement, metastatic site, histologic classification, histologic differentiation, family history of malignant tumors, presenting symptoms and survival rates were compared. RESULTS: One hundred patients were 50 years of age or under. Clinical, histopathologic characteristics and overall survival of the two groups did not differ. A higher rate of familial cancer syndromes was detected among young patients. CONCLUSIONS: The presentation and outcome of the disease in young patients do not differ from those of older patients. A significant family history of colorectal cancer in the young patients showed the need for screening whereas the outcome of metastatic disease was poor. In order to anticipate long survival, early detection and aggressive treatment is necessary.

Effect of cisplatin on skin metastasis in breast cancer patients.

BACKGROUND: Metastatic breast cancer is a common clinical entity, and its treatment is still a major clinical problem in modern oncology. Both cisplatin (CDDP) and 5-fluorouracil (5-FU) are effective agents. PATIENTS AND METHODS: In this retrospective study, the therapeutic efficacy and tolerability of CDDP and continuous infusion of 5-FU were evaluated in patients with pretreated metastatic breast cancer. 16 patients were surveyed. All of them were pretreated with anthracyclines in an adjuvant and/or therapeutic setting. Eight of them also received taxanes after the failure of anthracyclines. CDDP at 80 mg/m(2) for 1 day and 5-FU at 1,000 mg/m(2) as a continuous 24-hour infusion for 5 consecutive days were administrated every 3 weeks. RESULTS: 13 patients were included in response analysis. Because of severe toxicity, chemotherapy protocols of 3 patients were stopped after the first cycle. The objective response rate (partial response) was 46%. No complete response was observed. The median response duration was 5 (3.5-7) months in the response group. Favorable objective responses were observed more frequently in cases with skin metastasis. Five out of 6 patients who attained partial remission had skin metastasis. Response rates were similar in patients pretreated with taxanes and in those not pretreated with taxanes (75 vs. 80%). The most serious toxicity was myelosuppression (25%). CONCLUSIONS: Although this study is based on only a limited number of patients, the combination of CDDP and 5-FU can be recommended in patients refractory to both anthracyclines and taxanes and especially in cases of skin metastasis with a good performance status.

Cisplatin plus vinorelbine as a salvage regimen in refractory breast cancer.

AIMS AND BACKGROUND: Breast cancer refractory to known effective agents is one of the major clinical problems frequently encountered in practice. Cisplatin and vinorelbine are known to be active drugs in anthracycline-refractory cases. In this phase II study, the effectiveness and tolerability of cisplatin and vinorelbine was investigated when used in combination as a salvage regimen in the treatment of metastatic refractory breast cancer. STUDY DESIGN: Twenty-four patients with advanced refractory breast cancer who had been previously treated with a regimen containing doxorubicin were included in the study. Six of the 24 patients also received taxanes after failure of doxorubicin. Cisplatin at 80 mg/m2 on day 1 and vinorelbine at 25 mg/m2 on days 1 and 8 were given every 3 weeks. RESULTS: A total of 98 cycles of chemotherapy was given, with a median of 4/patient. The response rate was 25% (2 [8.3%] complete and 4 [16.7%] partial responses). The median survival rates were 14 months in responders and 5.5 months in nonresponders (P = 0.0282). One complete and one partial response were observed in patients previously treated with paclitaxel (overall response rate, 33%). The median response duration was 12.5 mo (range, 4-21) in complete and 4.5 mo (range, 1.5-13) in the partial response group. Grade 3 and 4 neutropenia occurred in 9 patients, with no toxic deaths. Grade 2-3 nausea and vomiting in 6 patients and grade 1 neuropathy in 1 patient were noted. CONCLUSIONS: Although the number of cases is insufficient to indicate that the combination will be effective, it is noteworthy in consideration of anthracycline and taxane refractory cases. A combination of cisplatin and vinorelbine seems to be a reasonable and acceptable choice as an alternative salvage regimen in such cases.

A phase I dose escalation study of high-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous peripheral blood stem cell transplantation (PBSCT) in patients with solid tumors and hematologic malignancies.

The purpose of this study was to determine the maximum tolerated dose of carboplatin administered with 500 mg/m2 thiotepa and 100 mg/m2 melphalan followed by autologous peripheral blood stem cell (PBSC) infusion in patients with refractory malignancies. Twenty-eight patients with refractory malignancies received high-dose thiotepa (500 mg/m2, melphalan (100 mg/m2) and escalating doses of carboplatin 900-1500 mg/m2) followed by infusion of cryopreserved autologous PBSCs. The maximum tolerated doses were determined to be 500 mg/m2 thiotepa, 100 mg/m2 melphalan and 1350 mg/m2 carboplatin. Two consecutive patients receiving 1500 mg/m2 carboplatin experienced grade 3 mucositis and colitis. Ten patients were enrolled at the maximum tolerated dose and none had grade 3-4 regimen-related toxicity and mortality. All patients at this level experienced grade 1-2 mucositis, 90% grade 1-2 gastrointestinal toxicity, 30% grade 1-2 cardiac and renal toxicity, and 10% experienced grade 1 hepatic toxicity. The median time to achieve a granulocyte count of 0.5x10(9)/l was 9 days (range 7-12 days) and platelet count of 20x10(9)/l was 10 days (range 7-15 days). Of eight patients with stage IV refractory breast cancer, even were evaluable for response, one patient on day 75 will be evaluated soon. Five of seven (71.5%) evaluable patients achieved a complete remission (CR) and two had no response. Of seven patients with non-Hodgkin's lymphoma (n = 4) or Hodgkin's disease (n = 3), five achieved a CR (71.5%). Thiotepa, melphalan and carboplatin can be administered in high doses with tolerable mucositis as the major side-effect. This combination has significant activity in patients with breast cancer, and phase II studies in patients with breast cancer and other chemotherapy-sensitive malignancies are warranted.

Neoadjuvant chemotherapy in locally advanced breast cancer: a preliminary report. Turkish Oncology Study Group.

AIMS AND BACKGROUND: A pilot study of neoadjuvant chemotherapy with cyclophosphamide-epirubicin-5-fluorouracil (FEC) was performed on 85 patients with locally advanced breast cancer. METHODS AND STUDY DESIGN: Patients received four cycles of neoadjuvant chemotherapy followed by surgery, radiotherapy and a treatment with cyclophosphamide-methotrexate-5-fluorouracil for three cycles. RESULTS: Major clinical response was obtained in 76 (89%) patients. Complete response was documented in 14 (17%) patients at pathologic examination of surgical specimen. Grade 1-2 nausea and vomiting was the most common (77%) side effect. Grade 2-3 alopecia was 66%. Grade 2-3 neutropenia occurred in 16% of patients. None of the patients developed febrile neutropenia. Sinus tachycardia was observed only in one patient. Three patients had a more than 10% decrease in the left ventricular ejection fraction without any clinical signs. Nine patients had progressive or stable disease and 4 did not undergo surgery or receive radiation therapy; thus 13 were excluded from survival analysis. After a median followup of 31 months (range, 15-41), disease-free survival and overall survival were 20 (range, 13-32) and 23 months (range, 17-32). CONCLUSIONS: The FEC combination is safe and effective for a neoadjuvant setting in locally advanced breast cancer. A longer follow-up is necessary for the end point results.

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 hypomagnesemia 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.

Primary gastrointestinal lymphomas in Turkey: a retrospective analysis of clinical features and results of treatment.

UNLABELLED: Thirty-three patients with primary gastrointestinal lymphoma (GIL) followed at Ankara University Medical School have been evaluated. The most frequent locations of the disease are the small intestine (48.4%) and the stomach (39.3%). The intermediate and high grade lymphomas constitute 84.8% of the cases. The mean age of the patients with small intestinal lymphoma is 28.7 years and 47.1 years for those with gastric lymphoma. The patients treated with surgery and chemotherapy (S+CT) have a longer survival than those treated with chemotherapy (CT) alone. IN CONCLUSION: 1) Small intestinal lymphoma occurs more frequently than gastric lymphoma in our study. 2) The median age of the Turkish patients with primary GIL is approximately 10 years less than those in the Western countries. 3) The therapeutic results of S+CT are superior to those of CT in the early stages of the disease.

Cisplatin plus VP-16 combination chemotherapy in advanced refractory breast cancer.

Twenty-nine patients with advanced refractory breast cancer were treated with cisplatin 20 mg/m2/d and VP-16 100 mg/d for 5 days every 3-4 weeks. Ten patients received mitomycin C 10 mg/m2 every 6 weeks additionally. Partial response was obtained in 10 of 26 evaluable patients (38%). The response rates for the group treated with and without mitomycin C were 40% and 37.5%, respectively. Median response duration was 5.5 months in partial responders. Median survival was 9.5 months for partial responders and 2 months for the rest of the patients. Cisplatin and VP-16 combination can be considered as a salvage treatment in heavily pretreated patients with advanced breast cancer.

Cigarette smoking among young physicians and their approach to the smoking problem of their patients.

We have undertaken a survey of 100 interns and 100 residents at University of Ankara Medical School to find out their smoking rates as well as their view of the smoking problem in Turkey and their approach to the patient who smokes. The smoking rate of interns and residents were comparable to those of the 146 nonmedical university students surveyed at the same time (31% and 37% versus 38%). Our results indicate that smoking residents have less confidence in their efficacy to influence the patients to quit smoking when compared to nonsmokers (34.2% versus 14.5%; p < 0.05). Likewise, they have a higher, though not significant, tendency not to counsel their patients than those who are not smoking. Therefore we conclude that a successful smoking cessation program in Turkey requires encouragement of the medical students and residents to quit smoking and better training of them with regard to smoking intervention methods in order to increase their confidence of efficacy.