Gokmen Aktas

Polymorphism of CYP3A4 and ABCB1 genes increase the risk of neuropathy in breast cancer patients treated with paclitaxel and docetaxel

Background Interindividual variability of pharmacogenetics may account for unpredictable neurotoxicities of taxanes. Methods From March 2011 to June 2015, female patients with operable breast cancer who had received docetaxel- or paclitaxel-containing adjuvant chemotherapy were included in this study. All patients were treated with single-agent paclitaxel intravenously (IV) 175 mg/m2 every 3 weeks for four cycles, or IV 80 mg/m2 weekly for 12 cycles, and IV 100 mg/m2 docetaxel for four cycles as adjuvant treatment. We evaluated the relationship between neurotoxicity of taxanes and single-nucleotide polymorphisms of ABCB1, CYP3A4, ERCC1, ERCC2, FGFR4, TP53, ERBB2, and CYP2C8 genes. Taxane-induced neurotoxicity during the treatment was evaluated according to the National Cancer Institute Common Toxicity Criteria version 4.03 prior to each cycle. Chi-squared tests were used to compare the two groups, and multivariate binary logistic regression models were used for determining possible risk factors of neuropathy. Results Pharmacogenetic analysis was performed in 219 females. ABCB1 3435 TT genotype had significantly higher risk for grade ≥2 neurotoxicity (odds ratio [OR]: 2.759, 95% confidence interval [CI]: 1.172–6.493, P: 0.017) compared to TC and CC genotype, and also CYP3A4 392 AA and AG genotype had significantly higher risk for grade ≥2 neurotoxicity (OR: 2.259, 95% CI: 1.033–4.941, P: 0.038) compared to GG genotype. For FDGF4 gene with AG and GG genotype, OR was 1.879 (95% CI: 1.001–3.525, P: 0.048) compared to AA genotype with regard to any grade of neuropathy risk. We could not find any other association of other genotypes with neurotoxicity grades. Conclusion ABCB1 3435 TT genotype and CYP3A4 392 AA/AG genotypes may be used as predictors of neurotoxicity during taxane chemotherapy.

Could erlotinib treatment lead to acute cardiovascular events in patients with lung adenocarcinoma after chemotherapy failure

Erlotinib, an epidermal growth factor receptor and tyrosine kinase inhibitor, is a targeted drug that was approved for the treatment of non-small-cell lung cancers and pancreatic cancers. Targeted tyrosine kinase inhibitors are known to have cardiotoxic effects. However, erlotinib does not have a statistically proven effect of increasing acute cardiovascular event (ACE) risk. Preclinical studies showed that beta agonist stimulation among rats that were administered erlotinib led to cardiovascular damage. Thus, there would be an aggregate effect of erlotinib on ACE, although it is not thought to be a cardiotoxic drug itself. In this paper, we present two non-small-cell lung cancer cases that developed ACE under erlotinib treatment.

Collision tumor consisting of primary follicular lymphoma and adenocarcinoma in the cecum: A case report and literature review.

The present study reports the case of a collision tumor consisting of follicular lymphoma (FL) and adenocarcinoma in the cecum of a 73-year-old man. To the best of our knowledge, the present study is the 11th case of a collision tumor consisting of colon adenocarcinoma and lymphoma to be reported in the literature, and the first case of cecum adenocarcinoma with low grade FL in the same segment of the cecum and the same regional lymph node to be reported. The present study reviewed the literature to determine treatment options for patients with collision tumors. The present patient was administered with adjuvant chemotherapy for T3N1M0 colon cancer following surgery, due to the dominance of colon adenocarcinoma in the collision tumor. Following the completion of treatment, progression of the untreated FL was observed. In the literature, patients with collision tumors are administered with chemotherapy for stage IV FL, and following the completion of treatment patients have presented with a recurrence of early stage colon adenocarcinoma. The recommended treatment for collision tumors is dependent on the dominant tumor; however, the treatment options for collision tumors in the literature appeared to exacerbate the other tumor. The characteristics of the tumors altered following chemotherapy, and immunological alterations in the tumors due to chemotherapy appear to have contributed to the exacerbation of the tumors. Therefore, patients with early-stage tumors should be considered at risk of recurrence of other malignancies, which are present in collision tumors.

Prognostic impact of initial maximum standardized uptake value of (18)F-FDG PET/CT on treatment response in patients with metastatic lung adenocarcinoma treated with erlotinib.

Purpose To investigate whether the initial maximum standardized uptake value (SUVmax) on fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has a prognostic significance in metastatic lung adenocarcinoma. Patients and methods Sixty patients (24 females, mean age: 57.9±12 years) with metastatic stage lung adenocarcinoma who used erlotinib and underwent 18F-FDG PET/CT at the time of diagnosis between May 2010 and May 2014 were enrolled in this retrospective study. The patients were stratified according to the median SUVmax value, which was found as 11. Progression-free survival (PFS) rates for 3, 6, and 12 months were examined for SUVmax values and epidermal growth factor receptor (EGFR) mutation status. Results The number of EGFR-sensitizing mutation positive/negative/unknown was 26/17/17, respectively, and the number of patients using erlotinib at first-line, second-line, and third-line therapy was 15, 31, and 14 consecutively. The PFS rates of EGFR mutation positive, negative, and unknown patients for 3 months were 73.1%, 35.3%, and 41.2% (P=0.026, odds ratio [OR]=4.39; 95% confidence interval [CI]: 1.45–13.26), respectively. The PFS rates of EGFR positive, negative, and unknown patients for 6 months were 50%, 29.4%, and 29.4% (P=0.267, OR: 2.4; 95% CI: 0.82–6.96), respectively. The PFS rates of EGFR positive, negative, and unknown patients for 12 months were 42.3%, 29.4%, 23.5% (P=0.408, OR: 2.0; 95% CI: 0.42–5.26), respectively. Thirty-one of 60 patients had SUVmax values ≤11. The PFS rates for 3, 6, and 12 months were 70.5%/28% (P=0.001, OR=9.0; 95% CI: 2.79–29.04), 61.7%/8% (P<0.001, OR=28.35; 95% CI: 5.5–143), and 52.9%/8% (P<0.001, OR=18.69; 95% CI: 3.76–92.9) for low SUVmax (≤11) group/high SUVmax (>11) group, respectively. Conclusion Initial SUVmax value on 18F-FDG PET/CT is found to be a prognostic factor anticipating the response to erlotinib for 3, 6, and 12-month rates of PFS in both EGFR-sensitizing mutation and wild-type tumor group.

Polymorphisms in the MTHFR gene are associated with recurrence risk in lymph node-positive breast cancer patients

Purpose The aim of this study is to clarify the relationship between recurrence risk of breast cancer and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms. Patients and methods Breast cancer patients who had undergone surgery in Gaziantep University Oncology Hospital between June 2005 and June 2012 were followed-up and retrospectively enrolled in this study. Blood samples were collected from all patients to assess MTHFR C677T polymorphisms. Stage according to tumor–node–metastasis system, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 status, grade of disease, menopausal status, and administered chemotherapy or hormonal therapy were recorded. Effects of these parameters on recurrence risk were evaluated using univariate analysis and multivariate binary logistic regression model. Results Association of MTHFR C677T polymorphisms with recurrence risk was evaluated in 298 patients whose median age was 47 years (range: 21–79 years). In all patients, age (odds ratio [OR] =0.953, P=0.005) and N3 lymph node status (OR =6.293, P=0.001) were found to affect the recurrence risk. While MTHFR homozygote genotype did not have an effect on recurrence risk in all patients, increased risk was observed in lymph node-positive subgroup (OR =4.271; 95% CI 1.515–12.023; P=0.006). Adjusting for age, tumor size (T), and node status (N), MTHFR homozygote genotype had more statistically significant risk for recurrence (OR =3.255; 95% CI 1.047–10.125; P=0.041). Conclusion MTHFR TT genotype was found to be associated with increased recurrence risk in patients with lymph node-positive breast cancer.

Complete response of a recurrent-metastatic liposarcoma with dedifferentiated histological features following the administration of trabectedin and review of literature.

The present case report defines a rare case of a liposarcoma with bone metastasis resulting in a complete remission (CR) following trabectedin treatment. The patient was referred with abdominal swelling and pain. A retroperitoneal mass was detected and described as dedifferentiated liposarcoma (DDLS). The mass was surgically removed and consequently adjuvant chemotherapy was administered. Three months after the completion of chemotherapy, patient presented with bone metastasis in thoracic and lumbar vertebrae. Vertebroplasty and radiotherapy (RT) was performed. After these therapies, bone pain persisted and bone scintigraphy showed increased activity in L4, T11, and T12 vertebrae. Zoledronic acid was added to trabectedin treatment. CR has been detected on bone scintigraphy and positron emission tomography-computed tomography (PET-CT) after 18 weeks. Previous cases about liposarcoma treated with trabectedin were mostly about the myxoid/round cell type (former name, currently known as myxoid liposarcoma (MLS)) and mostly reported partial responses. In this study, trabectedin was used for the treatment of a metastatic retroperitoneal DDLS and a CR was achieved.

Long-term survival with transarterial chemoembolization and radioembolization in a patient with cancers of unknown primary

Cancers of unknown primary (CUP) are histologically proven metastatic malignant tumors without an identified primary site before treatment. The common characteristics are early dissemination, lower response to chemotherapy and poor prognosis with short life expectancy. Treatment was directed according to the presence of localized or disseminated disease. The most frequent site of metastasis is the liver, which is a suitable target organ for arterial-directed therapies. We report a case of 53-year-old woman who was diagnosed with CUP and suspected with intracellular cholangiocellular carcinoma (ICC), presented with a very large, unresectable, chemotherapy-refractory hepatic mass and treated with transarterial chemoembolization and transarterial radioembolization and surprisingly followed for 48 months with minimally progressive and stable disease. Arterial-directed therapies, an important therapeutic option in unresectable liver tumors, can provide survival benefit even for ICC and CUP which are very large in size.

Assessment of platelet reactivity after the anthracycline-based chemotherapy via mean platelet volume: Does it act on anthracycline-induced cardiotoxicity?

1 Gokmen Aktas1, Tulay Kus2, Emre Kuş3, Murat Sucu4, Handan Haydaroglu Sahin5, Mustafa Pehlivan5, 1Department of Internal Medicine, Division of Medical Oncology, Kahramanmaraş Sütçü İmam University, School of Medicine, Kahramanmaraş, 2Department of Internal Medicine, Division of Medical Oncology, University of Gaziantep, Faculty of Medicine, Gaziantep Oncology Hospital, Gaziantep, 3Department of Cardiology, Sehitkamil State Hospital, Gaziantep, 4Department of Cardiology, University of Gaziantep, School of Medicine, Gaziantep, 5Department of Hematology, University of Gaziantep, School of Medicine, Gaziantep, Turkey Assessment of anthracycline-induced cardiotoxicity via MPV Assessment of platelet reactivity after the anthracyclinebased chemotherapy via mean platelet volume: Does it act on anthracycline-induced cardiotoxicity?

Maintenance treatment with gemcitabine have a promising activity on metastatic bladder cancer survival

OBJECTIVE To investigate the effects of gemcitabine maintenance treatment on survival in patients with metastatic bladder cancer. MATERIAL AND METHODS Gemcitabine maintenance monotherapy was administered following the standard platinum-gemcitabine therapy in patients with metastatic bladder cancer. Patients who had responded to standard treatment received maintenance gemcitabine therapy as 1000 mg/m2 on days 1 and 8 every three weeks until progression or development of unacceptable toxicity. The following clinical factors were noted: performance status, age, sex, stage, site of metastasis, choice of cisplatin-gemcitabine or carboplatin-gemcitabine, response rates to the initial chemotherapy. Progression-free survival (PFS) and overall survival (OS) for standard treatment, and following gemcitabine monotreatment and for maintenance gemcitabine therapy were calculated using Kaplan-Meier method. RESULTS A total of 88 patients with metastatic bladder cancer treated between February 2009 to October 2015 were evaluated retrospectively and 23 patients (26.1%) who had responded to six cycles of platinum-gemcitabine treatment were included in this study. Maintenance gamcitabine was administered for a median of 7 times (range 3-14 times). Grade 3 hematotoxicity according to the criteria of the Common Terminology Criteria of Adverse Events was observed in 7 (30.4%) patients. Median PFS of patients was 46 (range: 30-82) weeks for platinum-based treatment plus maintenance gemcitabine therapy. A higher median PFS was obtained in patients who were <65 year-olds, without organ metastasis with objective response rate, however, it was statistically insignificant. CONCLUSION Gemcitabine maintenance therapy in metastatic bladder cancer patients who did not shown progression after the standard platinum-gemcitabine treatment contributes to survival and presents low toxicity profile, when compared to historical controls.

Comparison of distress in breast cancer survivors treated with different adjuvant endocrine therapies: a single-centre cross-sectional study

ABSTRACT AIM: To compare the depression and anxiety scores among breast cancer (BC) survivors who received different adjuvant endocrine therapies. PATIENTS AND METHOD: A total of 154 patients (with 6 months to 10 years follow-up) were recruited in this cross-sectional study. The patients were divided into three groups according to the type of endocrine therapy: selective oestrogen receptor modulator (tamoxifen), third-generation aromatase inhibitors (AIs; e.g. anastrozole and letrozole), and luteinizing hormone realizing hormone (LHRH) analogue with tamoxifen. Patients’ age, menopausal status at diagnosis, educational level, marital status, and disease characteristics including stage, treatment, and follow-up period since diagnosis were noted. Beck Depression Inventory, Beck Anxiety Inventory, and Duke-University of North Carolina Functional Social Support Questionnaire were used to assess the depression, anxiety, and functional social support, respectively. Statistical significance of the associations was analysed using Spearman correlation, Student’s t, Mann–Whitney u, and ANOVA tests. RESULTS: Patients’ mean age was 49.8 (28–77) years. Age and perceived social support which are patient-related factors affected anxiety and depression scores, while disease-related factors did not affect. Patients who received LHRH analogue with tamoxifen presented more anxiety scores. Patients who received tamoxifen had more depression scores than those who received AIs. This may have been due to the fact that the tamoxifen group is composed of young and pre-menopausal patients. CONCLUSION: Young age and lower social support are important determinants of higher anxiety and depression scores. The use of LHRH analogue is one of the risk factors for the development of anxiety in BC survivors.