Ozan Balakan

Efficiency and Side Effects of Sorafenib Therapy for Advanced Hepatocellular Carcinoma: A Retrospective Study by the Anatolian Society of Medical Oncology

BACKGROUND Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via the RAF/ MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFR-β) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenib to life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy and side effects of sorafenib therapy in Turkey. MATERIALS AND METHODS Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median age was 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of the patients had Child scores meeting the utilization permit of the drug in our country (Child A). RESULTS A total of 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluable cases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%). Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reduced only in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%) diarrhea, and 2 (2%) vomiting. CONCLUSIONS This retrospective study demonstrated better efficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-free survival and overall survival findings were comparable. The side effect rates indicate that the drug was tolerated well. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patients with inoperable or metastatic HCC.

Adjuvant systemic chemotherapy with or without bevacizumab in patients with resected liver metastases from colorectal cancer.

Background: We aimed to investigate the impact of adjuvant systemic therapy with modern chemotherapy combinations on survival outcomes in patients with resected liver-confined metastases from colorectal carcinomas, and whether addition of bevacizumab (BEV) provides further benefit. Methods: A total of 229 consecutive patients who underwent resection for liver-confined colorectal liver metastases were retrospectively analyzed. Results: Of 229 patients, 204 who received chemotherapy with fluoropyrimidine-based (n = 27), irinotecan-based (n = 84) and oxaliplatin-based (n = 93) combinations were analyzed. Among these, 87 patients received BEV while 117 did not (NoBEV). With a median follow-up of 27 months after metastasectomy, the median recurrence-free survival (RFS) and overall survival (OS) were 17 and 53 months, respectively. OS rates at 3 and 5 years were 71% and 40%, respectively. No significant differences were found in the median RFS (p = 0.744) and OS (p = 0.440) among different chemotherapy regimens. The median RFS (p = 0.375) and OS (p = 0.251) were similar in BEV and NoBEV arms. In multivariate analysis, having 4 liver metastases was the only negative independent factor on both RFS and OS, while positive surgical margin was another negative independent factor for RFS. Conclusion: Chemotherapy type and addition of BEV have no impact on both RFS and OS in the adjuvant setting following complete resection of colorectal liver metastases.

Do fasudil and Y-27632 affect the level of transient receptor potential (TRP) gene expressions in breast cancer cell lines?

Breast cancer (BC) is the most frequent cancer type in women, and the mortality rate is high especially in metastatic disease. Ion channels such as the transient receptor potential (TRP) channels correlate with malignant growth and cancer progression. Hence, some authors have suggested that the expression levels of TRP channels may be used as a marker in the diagnosis and predicting the prognosis of BC. Also, in some recent studies, targeting TRP channels are suggested as a novel treatment strategy in BC. The aim of this study was to investigate the effect of two Rho-kinase (ROCK) inhibitors, fasudil and Y-27632, on the expression levels of TRP channel genes in breast cancer cell lines (ZR-75-1, MCF7, and MDA-MB-231) and breast epithelial cell line (hTERT-HME1). The expression levels of TRP genes were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). We found that fasudil had reduced the TRPC1, TRPV2 expression levels in the ZR-75-1, MCF7, and MDA-MB-231 cell lines. On the other hand, fasudil and Y-27632 had reduced TRPM6 expression levels in all cell lines. Y-27632 increased the expression levels of TRPC7 in all cell lines. In conclusion, this is the first study demonstrating that the inhibition of ROCK pathway changes the expression levels of some TRP genes. Also, our study has firstly shown that the expression levels of the TRP genes which are suggested as a diagnostic and prognostic biomarker in BC, were changed with the treatment of fasudil and Y-27632.

Possible anti-metastatic effect of Iloprost in a patient with systemic sclerosis with lung cancer: a case study

Systemic Sclerosis (SSc) is a chronic disease of unknown etiology which affects the vascular system and connective tissue. A wide series of studies showed an increased prevalence of cancer in patients with SSc than the normal population. Prostacyclin (PGI2) is an endogenously produced element that is basically synthesized by arachiodonic acid through prostacyclin synthesis in vascular system endothelial cells. Iloprost is a stable analogue of PGI2 which is used in the treatment of pulmonary arterial hypertension (PAH). In a limited number of animal models, the anti-metastatic activity of PGI2 is observed. Herein, we report iloprost treatment of a 60-year-old-woman with SSc, who lately developed PAH as a complication of her disease and lung adenocarcinoma as a co-incidence simultaneously. These two mortal complications were both treated successfully with inhaled iloprost until her death due to gastrointestinal complications of SSc.

Pathologic and Clinical Characteristics of Elderly Patients With Breast Cancer: A Retrospective Analysis of a Multicenter Study (Anatolian Society of Medical Oncology)

There is very little information about breast cancer characteristics, treatment choices, and survival among elderly patients. The purpose of this multicenter retrospective study was to examine the clinical, pathologic, and biologic characteristics of 620 breast cancer patients age 70 years or older. Between June 1991 and May 2012, 620 patients with breast cancer, recruited from 16 institutions, were enrolled in the retrospective study. Patients had smaller tumors at diagnosis; only 15% of patients had tumors larger than 5 cm. The number of patients who had no axillary lymph node involvement was 203 (32.7%). Ninety-three patients (15.0%) had metastatic disease at diagnosis. Patients were characterized by a higher fraction of pure lobular carcinomas (75.3%). The tumors of the elderly patients were also more frequently estrogen receptor (ER) positive (75.2%) and progesterone receptor (PR) positive (67.3%). The local and systemic therapies for breast cancer differed according to age. An association between age and overall survival has not been demonstrated in elderly patients with breast cancer. In conclusion, the biologic behavior of older patients with breast cancer differs from younger patients, and older patients receive different treatments.

Efficacy of sorafenib in patients with gastrointestinal stromal tumors in the third‑ or fourth‑line treatment: A retrospective multicenter experience

Sorafenib is a multi-targeted tyrosine kinase receptor inhibitor used to treat patients with advanced gastrointestinal stromal tumors (GISTs). The present study evaluated the efficacy and tolerability of sorafenib therapy for patients with GISTs. Between January 2001 and November 2012, 25 patients, from multiple centers, who had received sorafenib as the third- or fourth-line treatment for GISTs were investigated retrospectively. In total, 17 patients were male and eight were female. The median age was 54.0 years (range, 16–82 years). From the patients, 21 received imatinib for longer than six months and four received it for less than six months. The clinical benefit rate of sorafenib was 40.0%. Treatment-related adverse events were reported in 72% of patients. These adverse events were generally mild to moderate in intensity. The median progression-free survival (PFS) and overall survival (OS) times of the patients who received sorafenib were 7.2 and 15.2 months, respectively. The duration of imatinib usage was an independent prognostic factor for PFS and OS. Sorafenib is an effective treatment in patients with GISTs showing a clinical benefit rate of 40.0% and an acceptable tolerability.

A case of vemurafenib-induced polyarhritis in a patient with melanoma: how to manage it?

Vemurafenib is an inhibitor of the BRAF V600E mutation which is associated with tumor responses in patients with metastatic melanoma. Although it is generally well tolerated, common side effects of vemurafenib have been reported. Arthralgia is one of the more common adverse event associated with vemurafenib. We herein report a 49‐year‐old woman diagnosed with metastatic melanoma harboring the BRAF V600E mutation with severe polyarthritis associated with vemurafenib after 7 days of treatment. Sonographic examination of affected joints revealed synovitis and the patients articular symptoms were improved by analgesic and anti‐inflammatory treatment, including corticosteroids. During therapy with selective BRAF inhibitors, arthritis represents a new adverse event that can require dose reduction. In case of this adverse event, treatment with anti‐inflammatory drugs, such as ibuprofen and prednisone, should be initiated early to keep patients on treatment and to avoid drug discontinuation and tumor progression.

Treatment modalities in primary gastric lymphoma: the effect of rituximab and surgical treatment. A study by the Anatolian Society of Medical Oncology

Aim of the study Gastrointestinal lymphoma is the most common type of extranodal lymphoma and commonly involved site is the stomach. We have compared the superiority between treatment modalities for primary gastric lymphoma and we want to investigate efficacy of rituximab in gastric lymphoma. Material and methods Between April 2002 and December 2011, 146 patients with a histologically confirmed primary gastric lymphoma, initially diagnosed at eight different Cancer Centers within Turkey were evaluated retrospectively. According to the treatment modality, the patients were divided into chemotherapy (CT) alone, chemotherapy and radiotherapy (CRT), surgery and chemotherapy (SCT), surgery along with chemotherapy and radiotherapy (SCRT), and surgery (S) alone groups. Results Median follow-up period was 25.5 months. The 5-year EFS (event free survival) and OS (overall survival) rates for the patients were 55% and 62.3% respectively. In Log rank analysis of OS and EFS, we have identified levels of albumin and hemoglobine, IPI score, stage at diagnosis as factors influencing survival. In multivariate analysis of OS and EFS, only albumin and stage at diagnosis were factors independently contributing to survival. There was no statistically significant difference in terms of survival between different treatment modalities (p = 0.707 in EFS and p = 0.124 in OS). In analysis of patients treated with chemotherapy alone, there was no a statistically significant difference in terms of EFS and OS between chemotherapy regimens with or without rituximab in localized and advanced stage groups (p = 0.264 and p = 0.639). There was no statistical difference in survival rate (EFS and OS) between surgical or non-surgical treatment modalities for localized/advanced stage gastric lymphoma groups (p = 0.519 / p = 0.165). Conclusions There are several treatment options due to similar results in different treatment modalities. Also benefit of rituximab treatment in gastric lymphoma is still a controversial subject. Additional prospective trials are definitely required in order to clarify use of rituximab in treatment of extranodal gastric lymphoma.

Depression, anxiety and quality of life through the use of complementary and alternative medicine among breast cancer patients in Turkey

BACKGROUND AND AIM Breast cancer is the most common type of cancer amongst women today. The aim of this study was to examine the association between complementary and alternative medicine (CAM) and the quality of life (QoL), anxiety and depression and demographic characteristics of women with breast cancer. MATERIALS AND METHODS QoL was measured by the European Organization for Treatment and Research of Cancer quality of life core questionnaire (QLQ-C30, version 3.0) and anxiety and depression was measured by the hospital anxiety and depression scale. RESULTS In total, 122 patients with breast cancer were enrolled in the study and 50% (n=61) of them reported that they were using CAM. The most commonly used CAM methods were stinging nettle (57%) and prayer and spiritual healing (49%). No relationship was found between the use of CAM and the patients age, time to diagnosis, cancer stage, chemotherapy use, smoking and residence. However, the analyses showed a positive association between CAM and role functioning (P=0.014) and financial difficulties (P=0.011); and a negative association between CAM and emotional functioning (P=0.033). CONCLUSIONS Based on the previous studies, 20-83.3% of breast cancer patients among different countries and cultures used CAM. Our results suggested that the use of CAM among women is quite popular, but they showed no correlation between CAM usage and anxiety and depression. In addition, CAM usage was more common in breast cancer patients with a poor emotional and financial status.

Cetuximab-induced esophageal ulcer: the first report in literature.

Cetuximab, a monoclonal antibody to the extracellular domain of epidermal growth factor receptor (EGFR), is indicated for the treatment of metastatic colorectal cancers and head–neck cancers. Cetuximab is generally well tolerated but some side effects, such as skin rash, malaise, vomiting, diarrhea, hypomagnesemia, and hypersensitivity reactions, have been reported. Esophageal ulcer in patients receiving cetuximab treatment has not been described previously. We herein report a 59-year-old man diagnosed with metastatic rectal cancer with esophageal ulcers associated with cetuximab after five cycles of treatment. To the best of our knowledge, this is the first report that shows cetuximab may induce esophageal ulcers, which may be precursor lesions to a gastrointestinal tract perforation. (Published: 24 February 2014) Citation: Libyan J Med 2014, 9 : 23723 - http://dx.doi.org/10.3402/ljm.v9.23723