Nuriye Ozdemir

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.

Assessment of Prognostic Value of "Neutrophil to Lymphocyte Ratio" and "Prognostic Nutritional Index" as a Sytemic Inflammatory Marker in Non-small Cell Lung Cancer.

BACKGROUND Systemic inflammatory response was shown to play an important role in development and progression of many cancer types and different inflammation-based indices were used for determining prognosis. We aimed to investigate the prognostic effects of neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS NSCLC patients diagnosed in our institution were retrospectively reviewed. Demographic and clinicopathologic characteristics were recorded. NLR and PNI was calculated before the application of any treatment. RESULTS A total of 138 patients were included in the study. Patients were divided into two groups according to NLR (<3.24 or ≥3.24) and PNI (<49.5 or ≥49.5). While median overall survival was 37.0 (95% CI 17.5-56.5) months in the group with low NLR, it was calculated as 10.0 (95%CI 5.0-15.0) months in the group with high NLR (p<0.0001). While median overall survival was 7.0 (95%CI 3.5-10.5) months in the group with low PNI, it was calculated as 33.0 (95% CI 15.5-50.4) months in the group with high PNI (p<0.0001). Stage, NLR and PNI levels were evaluated as independent risk factors for overall survival for all patients in multivariate analysis (p<0.0001, p=0.04 and p<0.001, respectively). CONCLUSIONS NLR (≥3.24) and PNI (<49.5) at diagnosis is an independent marker of poor outcome in patients with NSCLC. NLR and PNI is an easily measured, reproducible prognostic tests that could be considered in NSCLC patients.

Prognostic factors and treatment outcomes in 93 patients with uterine sarcoma from 4 centers in Turkey.

INTRODUCTION Uterine sarcomas are a group of heterogenous and rare malignancies of the female genital tract and there is a lack of consensus on prognostic factors and optimal treatment. OBJECTIVE AND METHODOLOGY To perform a retrospective evaluation of clinicopathological characteristics, prognostic factors and treatment outcomes of 93 patients with uterine sarcomas who were diagnosed and treated at 4 different centers from November 2000 to October 2010. RESULTS Of the 93 patients, 58.0% had leiomyosarcomas, 26.9% malignant mixed Mullerian tumors, 9.7% endometrial stromal sarcomas, and 5.4% other histological types. According to the last International Federation of Gynecology and Obstetrics (FIGO) staging, 43.0% were stage I, 20.4% were stage II, 22.6% were stage III and 14.0 % were stage IV. Median relapse free survival (RFS) was 20 months (95% confidence interval (CI), 12.4-27.6 months), RFS after 1, 2, 5 years were 66.6%, 44.1%, 16.5% respectively. Median overall survival (OS) was 56 months (95% CI, 22.5-89.5 months), and OS after 1, 2, 5 years was 84.7%, 78%, 49.4% respectively. Multivariate analysis showed that age≥60 years and high grade tumor were significantly associated with poor OS and RFS; patients administered adjuvant treatment with sequential chemotherapy and radiotherapy had longer RFS time. Among patients with leiomyosarcoma, in addition to age and grade, adjuvant treatment with sequential chemotherapy and radiotherapy after surgery had significant effects on OS. CONCLUSION Uterine sarcomas have poor progrosis even at early stages. Prognostic factors affecting OS were found to be age and grade.

Childhood, adolescents, and young adults (≤25 y) colorectal cancer: study of Anatolian Society of Medical Oncology.

Purpose: To evaluate the clinicopathologic characteristics and treatment outcomes of young patients with colorectal cancer (CRC). Methods: Between May 2003 and June 2010, 76 patients were found eligible for this retrospective study. Age, sex, presenting symptoms, patients with acute presentation, family history, presence of polyps, histologic features, localization and stage of the tumor, treatment outcomes, time and site of recurrence, sites of metastasis, and survival outcomes were recorded from the patient files. Results: Seventy-six patients (55.3% male) with a median age of 23 years were evaluated. Patients were evaluated in 2 groups as follows: child-adolescent (0 to 19 y, n=20) and young adult (20 to 25 y, n=56). Sex and symptoms (abdominal pain and rectal bleeding) were significantly differed between the groups and acute presentation was close to statistical significance. Overall survival significantly increased in patients undergoing curative surgery (P<0.001). Other parameters affecting the survival was stage of disease (P=0.004). Response to palliative chemotherapy in metastatic patients (P=0.042) and postoperative adjuvant chemotherapy had a statistically significant survival advantage (P=0.028). Conclusions: Diagnosis of CRC should not be excluded solely on the basis of age. CRC features in young-adult patients are more similar to adults compared with that of child-adolescent patients according to the symptoms and presentation. In patients with CRC in this age group, curative surgery, adjuvant chemotherapy, and palliative chemotherapy provide survival advantage.

Efficacy and Toxicity of Gemcitabine Plus Docetaxel Combination as a Second Line Therapy for Patients with Advanced Stage Soft Tissue Sarcoma

PURPOSE To assess the safety and efficacy of a gemcitabine plus docetaxel regimen as a second line therapy for patients with advanced soft tissue sarcoma (STS) resistant to doxorubicin and ifosfamide-based therapy. PATIENTS AND METHODS Medical records of 64 patients with advanced STS who received gemcitabine plus docetaxel regimen as a second line treatment between May 2006 and June 2011 were examined. All patients had been previously treated with doxorubicin plus ifosfamide-based regimen at first line setting. Patients received gemcitabine 900 mg/m2 on days one and eight intravenously over 90 minutes, followed by docetaxel 75 mg/m2 on day eight intravenously over one hour. Cycles were repeated every 3 weeks. RESULTS The male-to-female ratio was 37/27 and the median age was 44 years (range; 19-67 years). Objective responses were observed in 13 (20.3%) patients (2 CR, 11 PR) and stable disease in 21 (32.8%). Total clinical benefit (CR+PR+SD) was observed in 34 (53.1%). Median overall survival (OS) was 18 months (95% confidence interval (CI):12.1-23.9) and Median time to progression (TTP) was 4.8 months (95% CI: 3.6-6). A total of 243 cycles of chemotherapy were administered. The median number of cycle was 3 (range; 1-11). The most common grade 3-4 hematologic toxicity was neutropenia (35.9%). The most common nonhematologic toxicities consisted of nausea/vomiting (37.5%), mucositis (32.8%), peripheral neuropathy (29.7%), and fatigue (26%). There was no toxicity-related death. CONCLUSION The combination of gemcitabine plus docetaxel is an active and tolerable regimen as a second line therapy for patients with advanced soft tissue sarcoma who have failed doxorubicin and ifosfamide-based therapy.

Current approaches for prophylactic cranial irradiation in extrapulmonary small cell carcinoma

Abstract Background: Small cell lung cancer (SCLC) patients, who have achieved complete or partial response after chemotherapy, should be followed with prophylactic cranial irradiation (PCI). PCI for extrapulmonary small cell carcinoma (EPSCC) is not routinely recommended. The purpose of this review is to discuss all aspects of PCI in management of EPSCC. Scope: The PubMed database and the database of online abstracts of the American Society of Oncology (ASCO), ASCO Genitourinary (GU) Cancers meetings and clinical trials were searched up to 15 October 2013 using the following search keywords: ‘SCC or EPSCC of each organ site and prophylactic cranial radiotherapy’. The language of screened abstracts and manuscripts was limited to English. The papers which included the largest case series and data of cases about prophylactic cranial radiotherapy and/or were published in the last 10 years were selected. Findings: Many single center studies showed low incidence of brain metastasis in patients with esophageal small cell carcinoma (SCC). Due to the low incidence of brain metastasis, PCI is not recommended for esophageal SCC. Genitourinary, colorectal, small bowel and appendix cranial metastatic SCCs are extremely rare. Therefore, PCI is not recommended. The frequency of brain metastasis of prostate small cell carcinoma is much higher (16–19%) compared to other counterparts of EPSCC. PCI can be performed in selected cases of prostate SCC. High rates (41%) of brain metastasis develop in head and neck SCC. PCI should be considered for patients with head neck SCC. Conclusion: In the literature, the brain metastasis incidence of EPSCC might vary from 1.7% up to 40%. In many patients with ESPCC, PCI is not recommended. However, we have to keep in mind that primary head and neck and prostate SCC are exceptions due to the high incidence of cranial metastasis; PCI should be recommended for these patients on an individual basis.

Successful treatment of chronic hiccup with baclofen in cancer patients.

Chronic hiccup is an infrequent but distressing symptom in patients with advanced cancer. A series of drugs (chlorpromazine, haloperidol, nifedipine, metoclopramide, baclofen) have been used to treat hiccup without definitive results. Some authors have suggested a possible role of baclofen in the treatment of chronic hiccup. We report three cases of chronic hiccup in patients with cancer successfully treated with baclofen.

Oral Etoposide for Platinum-Resistant and Recurrent Epithelial Ovarian Cancer: a Study by the Anatolian Society of Medical Oncology

BACKGROUND The aim of this study was to evaluate the efficacy and toxicity of long-term, low-dose oral etoposide as an advanced treatment option in patients with platinum resistant epithelial ovarian cancer. MATERIALS AND METHODS For the purposes of this study, 51 patients with histologically-confirmed, recurrent or metastatic platinum-resistant epithelial ovarian cancer (EOC) treated at six different centers between January 2006 and January 2011 were retrospectively evaluated. Patients were treated with oral etoposide (50 mg/day for a cycle of 14 days, repeated every 21 days). RESULTS Among the 51 platinum-resistant patients, 17.6% demonstrated a partial response and 25.5% a stable response. The median progression-free survival (PFS) was 3.9 months (95% CI, 2.1-5.7), while the median overall survival was 16.4 months (11.8-20.9). No significant relationship was observed between the pre-treatment CA 125 levels, post-treatment CA-125 levels and the treatment response rates (p=0.21). Among the 51 patients who were evaluated in terms of toxicity, grade 1 or 4 hematologic toxicity was observed in 19 (37.3%); and grade 1-4 gastrointestinal toxicity occurred in 15 patients (29.4%). CONCLUSIONS Chronic low-dose oral etoposide treatment is generally effective and well-tolerated in platinum-resistant ovarian cancer patients.

A comprehensive review of the role of the hedgehog pathway and vismodegib in the management of basal cell carcinoma

Abstract Background: Basal cell carcinoma (BCC) is the most common cancer. Most cases of BCCs are treated with only optimal surgical resection. However, unresectable, locally advanced or metastatic tumors might have potential to progress. In this patient group, there is no standardized treatment approach. Vismodegib is a new selective inhibitor of the hedgehog (Hh) pathway. This manuscript is aimed to review the efficacy of the Hh pathway inhibitor vismodegib in BCC patients with locally advanced or metastatic disease. Scope: Vismodegib showed positive results in clinical studies. A computerized search of the PubMed and American Society of Clinical Oncology Meeting abstracts was performed, by searching for the following keywords: ‘vismodegib’, ‘pathway’, ‘inhibitor’, and ‘targeted therapies for BCC’. The last search was done on 1 September 2014. Most of the vismodegib data depend on phase I and II trials. Findings: Preclinical and clinical studies have shown that Hh pathway activation occurs in BCC. In BCC patients the role of chemotherapy is not completely known. Although conventional chemotherapies like cisplatins increase the response rate in BCC, improvement in overall survival and progression free survival were not demonstrated. Results of both phase I and phase II studies have shown that vismodegib is a potential new treatment strategy for patients with locally advanced and metastatic BCC. As in previously published phase I trials, in the ERIVANCE BCC study the primary endpoint, objective response rate, significantly increased by 43% and 30% in patients with locally advanced and metastatic BCC, respectively. Because of the promising results in phase I and II trials, vismodegib was approved by the Food and Drug Administration (FDA) in the treatment of patients with BCC who are not suitable for surgery or radiotherapy or with relapsed locally advanced disease following surgery or metastatic disease. Conclusion: Recent trials have shown that vismodegib has produced promising activity in patients with locally advanced and metastatic BCC. The ongoing studies with vismodegib in other solid tumors and BCC will shed light on more certain treatment pathways.

Results of Adjuvant FOLFOX Regimens in Stage III Colorectal Cancer Patients: Retrospective Analysis of 667 Patients

Objective: The aim of this study was to assess the use of 5-fluorouracil (5-FU), leucovorin and oxaliplatin (FOLFOX) regimens in clinical practice according to their efficacy and toxicity. Methods: Patients who received oxaliplatin-containing regimens after curative resection for colorectal carcinoma from 10 different oncology centers between May 2004 and December 2009 were included in the study. All patients were treated with FOLFOX regimens. Patients with rectal carcinoma were also treated with chemoradiotherapy with 5-FU after 2 cycles of a FOLFOX regimen. Results: The median age of the patients was 56 years (range 17–78). Of the total 667 patients, 326 were given FOLFOX-4, 232 were given modified FOLFOX-4 and 109 were given FOLFOX-6. The distribution according to disease stage was 33 patients with stage IIIA colorectal cancer, 382 patients with stage IIIB and 252 patients with stage IIIC. The most common adverse events were neutropenia (54%), nausea (36.9%), neuropathy (38.2%) and anemia (33.1%) for all grades. The median follow-up time was 23 months (range 1–79). Three-year disease-free survival and overall survival were 65 and 85.7%, respectively. Conclusion: The different oxaliplatin-containing 5-FU-based adjuvant chemotherapy regimens in patients with stage III colorectal cancer seemed to be at least equal in terms of efficacy regardless of the method of 5-FU administration or oxaliplatin dose.