Ahmet Demirkazik

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.

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 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.

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.

Venous Thromboembolism in Patients with Cancer and Its Relationship to the Coagulation Cascade and Vascular Endothelial Growth Factor

Venous thromboembolism (VTE) is a well-recognized problem in malignancy. Patients with cancer who have VTE have a worse prognosis than other patients with cancer. Hypercoagulability in patients with cancer is related to malignancy itself and its treatment. These patients have multiple risk factors for thromboembolism, such as being immobilized, having central venous catheters, and receiving chemoradiation therapy. Cancer procoagulant, tissue factor, factor VIII, and thrombin have important roles in causing cancer-associated thromboembolism. Tumors require neovascularization for delivering oxygen and other nutrients. Therefore, angiogenesis facilitates tumor growth, invasion, and metastasis. New blood vessels formed by angiogenesis are thrombogenic. Hypercoagulability and tumor growth are closely related. Vascular endothelial growth factor (VEGF) is a proangiogenic factor that may also cause VTE in patients with cancer. The relationship between cancer, angiogenesis, VEGF, and thrombosis is reviewed herein. Studies are ongoing to enhance our understanding of this complex interaction.

The effect of venous thromboembolism on survival of cancer patients and its relationship with serum levels of factor VIII and vascular endothelial growth factor: a prospective matched-paired study.

BACKGROUND Venous thromboembolism (VT) increases mortality and morbidity in cancer patients. The primary aim of this study was to evaluate the effect of VT on the survival of cancer patients and its relationship with serum vascu-lar endothelial growth factor (VEGF) and plasma factor VIII levels. PATIENTS AND METHODS Eighty-two patients with locally advanced or metastatic cancer were included in this study between September 2001 and March 2004, and 31 of them had VT. Fifty-one matched-paired cancer patients without VT were prospectively selected as a control group in the same period. Criteria for the selection of control group patients were hav-ing the same malignancy, stage, metastatic site, performance status and age (5 years) as patients in the VT group. RESULTS Plasma factor VIII and serum D-dimer levels in the VT group were significantly higher than those in the control group (p=0.030 and p=0.016, respectively). However, mean serum VEGF levels were similar in both groups (p=0.199). In the VT group, the median survival of patients who had higher serum VEGF levels (>150 pg/mL) was significantly shorter than that of patients in the same group with lower serum VEGF levels (p=0.005). The median survival of the VT group was 14 months, whereas it was 25 months in the control group (p=0.199). CONCLUSION There was a worse prognostic trend for cancer patients with VT. Nevertheless, the difference in survival was not statistically significant between the groups. Plasma factor VIII and serum D-dimer levels might have prognostic value in cancer patients with VT. Cancer patients with VT and higher serum VEGF levels had a significantly poorer prognosis.

Association of ABO blood group and risk of lung cancer in a multicenter study in Turkey.

BACKGROUND The ABO blood groups and Rh factor may affect the risk of lung cancer. MATERIALS AND METHODS We analyzed 2,044 lung cancer patients with serologically confirmed ABO/Rh blood group. A group of 3,022,883 healthy blood donors of Turkish Red Crescent was identified as a control group. We compared the distributions of ABO/Rh blood group between them. RESULTS The median age was 62 years (range: 17-90). There was a clear male predominance (84% vs. 16%). Overall distributions of ABO blood groups were significantly different between patients and controls (p=0.01). There were also significant differences between patients and controls with respect to Rh positive vs. Rh negative (p=0.04) and O vs. non-O (p=0.002). There were no statistically significant differences of blood groups with respect to sex, age, or histology. CONCLUSIONS In the study population, ABO blood types were associated with the lung cancer. Having non-O blood type and Rh-negative feature increased the risk of lung cancer. However, further prospective studies are necessary to define the mechanisms by which ABO blood type may influence the lung cancer risk.

A randomized trial of four cycles of adjuvant AC (adriamycin + cyclophosphamide) ± two cycles of EP (etoposide + cisplatin) in node positive patients with breast cancer

BACKGROUND Four cycles of AC have been accepted as the standard chemotherapy in breast cancer. In the present randomized study we aimed to assess the efficacy of adjuvant etoposide + cisplatin (EP) combination following four cycles of standard adriamycin + cyclophosphamide (AC) in premenopausal patients with operable breast cancer and axillary lymph node metastasis. PATIENTS AND METHODS Premenopausal patients with positive axillary lymph nodes following curative modified radical mastectomy were randomized to either four cycles of AC (82 patients) or four cycles of AC + two cycles of EP (83 patients). RESULTS Median follow-up is 72 months. All randomized and eligible patients are included in the analysis (AC: 80 patients, AC + EP: 78 patients). The five-year disease-free survival (DFS) for the AC + EP group was significantly better when compared to AC group (45.5% vs. 30.4%; P = 0.048). Again, the five-year overall survival (OS) of the whole group was in favor of AC + EP arm, though without statistical significance (68.6% vs. 59.1%; P = 0.247). CONCLUSION Two cycles of EP following four cycles of AC decreased the relapse rate in operable breast cancer patients.

Phase II study of cisplatin and dacarbazine for metastatic colorectal carcinoma resistant to 5-fluorouracil.

Twenty-six patients with metastatic colorectal cancer were given cisplatin (CDDP) and dacarbazine (DTIC). Patients who relapsed while receiving adjuvant 5-fluorouracil (FU) or had 5-FU-resistant metastatic disease were included. Median age was 52 years and the male-to-female ratio was 1. Performance status (ECOG) was 3 in 5 patients and 0–2 in the remainder. CDDP (20 mg/m2/day i.v.) and DTIC were given (250 mg/m2/day i.v.) on days 1–5. The treatment was repeated every 3 weeks until disease progression. Total response rate was 19.2% (95% confidence interval: 4.5–34.3%) with one clinical complete response (3.8%) and 4 partial responses (15.4%). Median response duration was 5 months. Median survival for the whole group and for responders was 6 and 8 months, respectively. In conclusion, CDDP + DTIC combination has modest activity in patients with colorectal cancer resistant to 5-FU treatment.