Ozkan Kanat

Protective Effect of Amifostine Against Toxicity of Paclitaxel and Carboplatin in Non-small Cell Lung Cancer

AbstractAim: In this study we determined the protective role of amifostine against the side effects of the combination of paclitaxel and carboplatin in patients with non-small cell lung cancer (NSCLC). Patients and Methods: Chemo-naive patients with NSCLC were eligible. Thirty-eight patients were randomized to receive paclitaxel 175 mg/m2 and carboplatin AUC=6 with amifostine 910 mg/m2 (group B) or chemotherapy alone (group A). The occurrences of hematologic, neurologic, cardiologic toxicities, and ototoxicity were evaluated. Results: All patients completed the six scheduled cycles of therapy. A total of 114 cycles of chemotherapy was given in both groups. Neutropenia grade 3–4 was observed in 11 cycles (9.6%) in group A and 19 cycles (16.6%) in group B (p=0.16). Paresthesia grade 1 or 2 was observed in 18 of 19 patients of group A and in 8 of 19 patients of group B, following the sixth cycle of chemotherapy (p=0.018). Two patients of group B and nine patients of group A suffered from sensory motor impairment grade 2 (p=0.029). There was no clinical evidence in any patient for deterioration in cardiac function. Asymptomatic and transient sinus bradycardia or ventricular premature beats developed in four patients. None of the patients reported vertigo, tinnitus, or hearing loss. Conclusion: The addition of the amifostine to the combination of paclitaxel and carboplatin may prevent or reduce the incidence of neurotoxicity in the treatment of NSCLC. Amifostine does not appear to have a preventive role in neutropenia.

Single-agent irinotecan as second-line treatment for advanced gastric cancer

Aim To investigate the activity and toxicity of irinotecan (CPT-11) as a single agent in patients with advanced gastric cancer after failure of previous 5-fluorouracil-based combination chemotherapy. Patients and methods Sixteen patients with advanced gastric received CPT-11, 350 mg/m2 every 21 days. The median age of the patients was 54.6 years; ECOG performance status was 0-1 in 14 patients and 2 in 2 patients. Dominant metastatic sites included liver, lung, lymph nodes and peritoneum. Results No complete response was observed. Two patients (12.5%) achieved a partial response to treatment. One patient (6.25%) had a minor response. Ten patients (62.5%) had progressive disease on therapy, and 3 patients (18.75%) had stable disease. The median survival of all 16 patients was 5 months. Grade 3 neutropenia was observed in 3 patients (18.75%), grade 4 thrombocytopenia in 1 patient (6.25%), and grade 3 anemia in 1 patient (6.25%). Three patients (18.75%) suffered from grade 3 diarrhea. Conclusions CPT-11 is moderately active and a well-tolerated regimen for selected advanced gastric cancer patients who experience disease progression after receiving first-line treatment.

XRCC1 Gene Polymorphisms and Risk of Lung Cancer in Turkish Patients

Abstract Polymorphisms in the X-ray repair cross complementing 1 (XRCC1) gene have been found to be associated with susceptibility to various types of cancers. We investigated the association between the XRCC1 gene Arg399Gln polymorphism and the susceptibility to lung cancer in Turkish patients. To determine the association of this polymorphism with the risk of lung cancer in Turkish patients, a hospital-based case-control study was designed, involving 67 patients with lung cancer and 60 control subjects with no cancer history who were matched for age and gender. XRCC1 genotypes (Arg/Arg, Arg/Gln, and Gln/Gln) were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis on genomic DNA. No statistically significant relationship was determined between the lung cancer and control groups (p>0.05). Among the patients, 61% were Arg/Arg, 28% were Arg/Gln, and 11% were Gln/Gln. Among the controls, 50% were Arg/Arg, 38% were Arg/Gln, and 12% were Gln/Gln. There was no difference in the distribution of XRCC1 genotypes or the frequencies of the Arg (75% versus 69%) and Gln (25% versus 31%) alleles between the lung cancer patients and controls. Our results suggest that the XRCC1 gene Arg399Gln polymorphism is not associated with an increased risk for the development of lung cancer in Turkish patients.

Comparison of uroprotective efficacy of mesna and amifostine in Cyclophosphamide- induced hemorrhagic cystitis in rats

BACKGROUND Hemorrhagic cystitis (HC) is a dose limiting side effect of cyclophosphamide (CYP). AIM In this study, we aimed to investigate the role of amifostine in the protection of CYP-induced HC and compare its efficacy with mesna. SETTING AND DESIGN This animal study was conducted in the Experimental Animals Breeding and Research Center of the Medical Faculty of Uludag University. MATERIALS AND METHODS Male Wistar rats (150-200 g; 10 rats per group) were randomly assigned to four groups. Group I (control group) received no drugs, group II received CYP (200 mg/kg, i.p.) alone, group III received amifostine (200 mg/kg, i.p.) and CYP, and group IV received CYP and mesna (40 mg/kg, i.p.) immediately and 4 and 8 h after administration of CYP. Bladders of animals were assessed macroscopically and histologically 24 h later. Gross assessment for presence of edema and hemorrhage and histological evaluation of damage to the bladder were scored according to Grays criteria. STATISTICAL ANALYSIS USED For macroscopic and microscopic data, we used statistical evaluation by Kruskal-Wallis nonparametric analysis of variance followed by the Mann-Whitney U-test. RESULTS All the animals in group II had evidence of HC. Significant histological damage and macroscopic changes were present in this group compared to control group (P<0.001). The median scores for bladder damage in group III and IV were significantly lower compared to group II (P<0.001). When the median scores for bladder damage of group I, III, and IV were compared, there was no significant difference among these groups. CONCLUSION This study demonstrated the efficacy of amifostine in prevention of cyclophosphamide-induced hemorrhagic cystitis.

Small cell carcinoma of the urinary bladder. A clinicopathologic study of five cases

Aims and Background Small cell carcinoma of the bladder (SCCB) is a rare entity characterized clinically by an aggressive behavior with a high incidence of systemic metastases. We report the clinicopathologic findings of five cases. Methods We reviewed five consecutive patients with SCCB treated at our institute. In each case the following clinical data were recorded: age, sex, presenting symptoms, endoscopically determined location of the tumor, clinical staging, node involvement (if any), site of metastases (if any), treatment, follow-up and outcome. Results There were four male and one female patients, age range 42 to 68 years, mean 57.6 years. The clinical presentation was not different from conventional transitional cell carcinoma, with hematuria being the most frequent complaint (four cases). Microscopic examination revealed oat cells in three cases and an intermediate variant in one. At the time of diagnosis the tumors were staged as T3bN2M0, T2N2M0, T4N0M0, T3aN0M0, and T2N0M0. Primary therapy consisted of radical cystectomy alone (one case), transurethral resection (TUR) alone (one case), TUR with chemotherapy (two cases), or TUR with chemotherapy and radiotherapy (one case). Four patients died of progressive disease, with survival from the time of diagnosis ranging from 7 to 16 months (mean, 12.2 months). One patient died of myocardial infarction (unrelated to the primary disease) one month after diagnosis. Conclusion Our study indicates that primary small cell carcinoma of the urinary bladder is as aggressive as its pulmonary counterpart and the overall prognosis of this tumor is very poor.

Phase II Study of Gemcitabine Plus Paclitaxel in Metastatic Breast Cancer Patients with Prior Anthracycline Exposure

Chemotherapy provides palliation and modest prolongation of symptom-free survival in metastatic breast cancer. Taxane containing regimens are commonly considered to be among the initials in metastatic setting due to earlier use of anthracyclines in the course of breast cancer. Therefore, we conducted this Phase II study to assess efficacy and safety of gemcitabine plus paclitaxel (GT) combination therapy in anthracycline pretreated metastatic first-line setting. Patients and Methods: The study enrolled 26 women with pathologically confirmed and measurable metastatic breast cancer who were previously treated with anthracycline but no prior chemotherapy for metastatic disease. Twenty six and twenty four patients were eligible for toxicity and efficacy evaluations respectively. Mean age was 47.3 years and median ECOG performance status was 0. Twenty patients (76.9 percent) had visceral metastases, most commonly located in liver and lung. Treatment schedule was as follows: paclitaxel 175 mg/m2 was administered intravenously in 3 hours on Day 1 and gemcitabine 1000 mg/m2 was administered intravenously in 30 minutes on Day 1 after paclitaxel application, and on Day 8 every 21 days. Results: Objective response rate was 41.7 percent (95 percent CI: 21.9–61.4) with 16.7 percent (95 percent CI: 1.7–31.6 percent) CR, and 25.0 percent (95 percent CI: 7.6–42.3 percent) PR. Median time to progression and overall survival were 9.6 and 14.5 months, respectively. Grade 3–4 toxicity was observed in 34.6 percent (9) patients. Treatment of two patients was discontinued due to toxicity, consisting of Grade 3 hypersensitivity reactions and Grade 4 infections in one patient each. Dose reductions due to myelotoxicity were performed in 4 (15.3 percent) patients. Hematologic toxicities were generally manageable with appropriate dose modifications and supportive care. Conclusion: Gemcitabine and paclitaxel combination regimen is effective and has manageable toxicity profile as first line metastatic setting.

Comparison of three different treatment modalities in the management of cancer cachexia

AIMS AND BACKGROUND The optimal treatment of cancer cachexia remains unknown. In this study, we compared the efficacy of three different treatment modalities in the management of cancer cachexia. METHODS Sixty-two assessable cachectic cancer patients were randomized to one of the following three arms: 1) megesterol acetate (MA) plus meloxicam (n = 23); 2) MA plus meloxicam plus oral eicosapentaenoic acid (EPA)-enriched nutritional supplement (n = 21); or 3) meloxicam plus oral EPA-enriched nutritional supplement (n = 18). Treatment duration was 3 months. RESULTS The treatment arms were well balanced at baseline. The primary efficacy (body weight and lean body mass) and secondary efficacy (body mass index, quality of life, and serum levels of IL-6 and TNF-α) parameters improved after treatment in all three arms. There were no statistically significant differences between treatment groups in the mean percentage changes in all efficacy parameters from baseline to end of study. CONCLUSIONS MA plus meloxicam or EPA supplement plus meloxicam may be effective treatment options in the management of cancer cachexia. The combined use of these agents does not provide further advantages.

Primary small cell carcinoma of the breast: report of seven cases and review of the literature

AIMS AND BACKGROUND The aim of the study was to analyze the clinicopathological characteristics, treatment modalities, and clinical outcome of patients with primary small cell carcinoma of the breast. METHODS Fifty-three cases of primary small cell carcinoma of the breast were identified; 7 cases in this series and 46 from the English-language medical literature. RESULTS There were 52 females and 1 male. The mean age was 53 years. Tumor size ranged from 1 to 18 cm (mean, 4.53). Axillary node metastasis was present in 61.7%. Only one patient had distant metastases at presentation. The presence of hormone receptors was reported in 24.5% of the tumors. Modified radical mastectomy was the most common surgical procedure and was performed in 50.9% of the patients. Adjuvant radiotherapy was administered to 39.6% of the patients, and 69.8% underwent chemotherapy. Thirteen percent of patients received adjuvant tamoxifen therapy. The mean follow-up was 20.75 months (range, 3-60), and 10 of 53 cases (18.9%) died of metastatic disease. CONCLUSIONS The prognosis of primary small cell carcinoma of the breast largely depends on the initial stage of the disease. Multimodality treatment including surgery, radiotherapy and chemotherapy seems to be the most appropriate strategy for early disease. Chemotherapy is usually unsuccessful in treating metastatic disease.

Immunohistochemical expression of excision repair cross-complementing 1 (ERCC1) in non-small-cell lung cancer: implications for patient outcome

IntroductionThe identification of novel prognostic markers may help to better assess survival probability in different subgroups of patients with non-small-cell lung cancer (NSCLC) and to tailor treatment according to the molecular profile of the tumour.AimWe sought to examine whether the immunohistochemical expression of excision repair cross-complementing 1 (ERCC1), an essential component of the nucleotide excision repair pathway, may predict prognosis in NSCLC.Material and methodFormalin-fixed paraffin-embedded tumour samples from 44 Turkish patients with NSCLC treated by adjuvant platinum-based chemotherapy were included in the study. Immunohistochemical expression levels of ERCC1 were correlated with clinical outcomes by Kaplan-Meier curves and multivariable Cox proportional hazards regression analysis.ResultsA total of 29 patients had ERCC1-negative tumours while 15 had ERCC1-positive tumours. The mean progression-free survival (PFS) was significantly lower in patients with ERCC1-positive tumours (13±2 months) than in those with ERCC1-negative tumours (27±5 months, p<0.05). Similarly, the mean overall survival (OS) was significantly lower in patients with ERCC1-positive tumours (20±3 months) than in those with ERCC1-negative tumours (33±5 months, p<0.05). After allowance for potential confounders, Cox regression analysis demonstrated that ERCC1 expression was significantly associated with both PFS and OS (both p<0.05).ConclusionThis study provides support for the prognostic value of ERCC1 immunohistochemical expression in patients with NSCLC treated by adjuvant platinum-based chemotherapy. If independently confirmed, these findings may improve prognostic stratification in this group of patients.

Modified outpatient dexamethazone, cytarabine and cisplatin regimen may lead to high response rates and low toxicity in lymphoma.

Objective: Our purpose was to investigate the efficacy of and establish a toxicity profile for a modified regimen of dexamethasone, cytarabine and cisplatin (DHAP) for lymphoma outpatients. Subjects and Methods: Fifty-one lymphoma patients, 26 with Hodgkin’s disease and 25 with non-Hodgkin’s lymphoma, were included. The patients’ median age was 32 years (range: 17–61). Twenty had progressive/refractory disease and 31 relapsed disease. Twenty-five were in clinical stage I/II and 26 in clinical stage III/IV before the initiation of salvage chemotherapy. DHAP consisted of dexamethasone (40 mg i.v. on days 1–4), cytarabine (2 g/m2 i.v. as 3-hour infusion on days 2 in the evening and 3 in the morning) and cisplatin (35 mg/m2 as 2-hour infusion on days 1–3) were administered every 21 days. A total of 154 cycles of modified DHAP were administered, with a median of 3 cycles per patient (range: 2–4). Results: The main toxicity was myelosuppression. WHO grade III–IV neutropenia and grade III–IV thrombocytopenia were observed in 27 (52.9%) and 21 (41%) patients, respectively. The overall response rate (85% for Hodgkin’s disease and 95% for non-Hodgkin’s lymphoma) was 88.3% (39.2% complete response and 49.1% partial response). Conclusion: The results showed that this outpatient schedule of DHAP was well tolerated and an effective salvage regimen.