Muhammed Ali Kaplan

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.

Is sunitinib-induced hypothyroidism a predictive clinical marker for better response in metastatic renal cell carcinoma patients?

Background: The main goal of this study was to examine whether the occurrence of hypothyroidism during sunitinib therapy in patients with metastatic renal cell carcinoma (mRCC) is associated with a better outcome. Methods: The study enrolled 81 patients with pathologically proven mRCC who were treated with sunitinib between March 2008 and June 2013.Thyroid function evaluation comprised (free-thyroxine) FT4 and thyroid-stimulating hormone (TSH) before treatment and at day 1 of each 6-week cycle. Survival analysis was performed using the Kaplan–Meier method, and the differences among the groups were determined using the log-rank test. Results: Hypothyroidism occurred in 30 (37%) of 81 patients within a median 3 months (range 1–18) of treatment initiation. There was a statistically significant correlation between the occurrence of hypothyroidism during treatment and the rate of objective remission (ORR) (hypothyroid patients vs euthyroid patients: 46.7 vs 13.7%, respectively; P = 0.001). Median progression-free survival (PFS) was 10 (95% CI 6.13–13.8) months in the euthyroid patients, and 17 (95% CI 9.33–24.6) months in the hypothyroid patients (P = 0.001). The median overall survival (OS) was 39 (95% CI 25.4–52.5) months in the hypothyroid patients and 20 (95% CI 14.7–25.2) months in the euthyroid patients (P = 0.019). Conclusions: The occurrence of hypothyroidism during treatment in patients was significantly associated with longer PFS, OS and better ORR in the current study.

Lack of Prognostic Value of Mean Corpuscular Volume with Capecitabine Therapy in Metastatic Breast Cancer

BACKGROUND Capecitabine is an oral fluoropyrimidine derivative which is frequently used alone or in combination regimens for the treatment of metastatic breast cancer. Although overall and progression free survivals have increased in recent years with the use of new generation drugs, predictive factors that would further improve the outcomes are needed. Previous studies have demonstrated the relation between post-treatment increase in mean corpuscular volume (MCV) and predicting therapy response as well as survival. The present study investigated the clinical impact of MCV elevation in metastatic breast cancer patients treated with capecitabine. MATERIALS AND METHODS The data of a total of 82 patients from three centers followed between June 2005 and June 2013 were retrospectively analyzed. The demographic data and hormone receptor status of the patients, as well as initial examination before and after treatment and data concerning progression were recorded. MCV ≥ 100 fl was considered as macrocytosis. Capecitabine was given at a dose of 2500 mg/m2 daily for 14 days every three weeks. Pre-treatment and post-treatment MCV and other parameters of complete blood count were recorded. Post-treatment initial evaluation was performed after 2 cycles of therapy. RESULTS The median age of the patients was 46.5 years (range 26-72 years) and 54% were premenopausal. Performance status was ECOG 0 and 1 in 81 (99%) patients. The median number of cycles for capecitabine therapy was 5 (min-max: 2-18). The median ΔMCV level (post-treatment values at sixth week - baseline) was 6.4. Whilst ΔMCV was ≥ 6.4 in 42 patients, it was <6.4 in 40 patients. Clinical benefit (complete response+partial response+stable disease) was observed in 37 (88%) of 42 patients with a median ΔMCV ≥ 6.4 and in 30 (75%) of 40 patients with ΔMCV <6.4 with no statistically significant difference (p=0.158). No significant difference was determined between the group with ΔMCV ≥ 6.4 and the group with ΔMCV <6.4 in terms of progression-free survival (11 vs 12 months) (p=0.55) and overall survival (20 months vs. 24 months) (p=0.11). CONCLUSIONS The identification of new predictive markers in metastatic breast cancer is very important. In some recent studies, increase in MCV has been suggested as a marker in tumor response. In the present study, however, no significant difference was determined between tumor response and increase in MCV. Further studies including higher numbers of patients are needed to determine whether increase in MCV is a predictive marker or not.

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.

Significance of Hormone Receptor Status in Comparison of 18F -FDG-PET/CT and 99mTc-MDP Bone Scintigraphy for Evaluating Bone Metastases in Patients with Breast Cancer: Single Center Experience

BACKGROUND Fluorine-18 deoxyglucose positron emission tomography computed tomography (18F-FDG-PET/ CT) and bone scintigraphy (BS) are widely used for the detection of bone involvement. The optimal imaging modality for the detection of bone metastases in hormone receptor positive (+) and negative (-) groups of breast cancer remains ambiguous. MATERIALS AND METHODS Sixty-two patients with breast cancer, who had undergone both 18F-FDG-PET/CT and BS, being eventually diagnosed as having bone metastases, were enrolled in this study. RESULTS 18F-FDG-PET/CT had higher sensitivity and specificity than BS. Our data showed that 18F-FDG- PET/CT had a sensitivity of 93.4% and a specificity of 99.4%, whiel for BS they were 84.5%, and 89.6% in the diagnosis of bone metastases. κ statistics were calculated for 18F-FDGPET/CT and BS. The κ-value was 0.65 between 18F-FDG-PET/CT and BS in all patients. On the other hand, the κ-values were 0.70 in the hormone receptor (+) group, and 0.51 in hormone receptor (-) group. The κ-values suggested excellent agreement between all patient and hormone receptor (+) groups, while the κ-values suggested good agreement in the hormone receptor (-) group. CONCLUSIONS The sensitivity and specificity for 18F-FDG-PET/CT were higher than BS in the screening of metastatic bone lesions in all patients. Similarly 18F-FDG-PET/CT had higher sensitivity and specificity in hormone receptor (+) and (-) groups.

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.

Is there any significance of lung cancer histology to compare the diagnostic accuracies of (18)F-FDG-PET/CT and (99m)Tc-MDP BS for the detection of bone metastases in advanced NSCLC?

Aim of the study Bone scintigraphy (BS) and fluorine-18 deoxyglucose positron emission tomography computed tomography (18F-FDG-PET/CT) are widely used for the detection of bone involvement. The optimal imaging modality for the detection of bone metastases in histological subgroups of non-small cell lung cancer (NSCLC) remains ambiguous. The aim of this study was to compare the efficacy of 18F-FDG-PET/C and 99mTc-methylene diphosphonate (99mTc-MDP) BS in the detection of bone metastases of patients in NSCLC. Specifically, we compared the diagnostic accuracies of these imaging techniques evaluating bone metastasis in histological subgroups of NSCLC. Material and methods Fifty-three patients with advanced NSCLC, who had undergone both 18F-FDG-PET/CT and BS and were eventually diagnosed as having bone metastasis, were enrolled in this retrospective study. Results The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 18F-FDG-PET/CT and BS were 90.4%, 99.4%, 98.1%, 96.6%, 97.0% and 84.6%, 93.1%, 82.5%, 93.2, 90.8%, respectively. The κ statistics were calculated for 18F-FDG-PET/CT and BS. The κ-value was 0.67 between 18F-FDG-PET/CT and BS in all patients. On the other hand, the κ-value was 0.65 in adenocarcinoma, and 0.61 in squamous cell carcinoma between 18F-FDG-PET/CT and BS. The κ-values suggested excellent agreement between all patients and histological subgroups of NSCLC. Conclusions 18F-FDG-PET/CT was more favorable than BS in the screening of metastatic bone lesions, but the trend did not reach statistical significance in all patients and histological subgroups of NSCLC. Our results need to be validated in prospective and larger study clinical trials to further clarify this topic.

Can LMWH improve the outcome of patients with inoperable stage III non-small cell lung cancer?

Aim of the study Lung cancer is the most common malignancy, accounting for one-third of all deaths from cancer. Some studies have shown that low molecular weight heparin (LMWH) significantly prolongs the survival of patients with non-small cell lung cancer (NSCLC). The aim of this study was to determine the effects of treating inoperable stage III NSCLC with LMWH in addition to concurrent chemoradiotherapy. Material and methods Eighty-two patients with inoperable stage III NSCLC were evaluated at Dicle Universitys Medical Oncology Department between 2005 and 2010. All patients were treated with concurrent chemoradiotherapy (CRT) with or without LMWH (enoxaparin 4000 IU/day) depending on the patients risk of thrombosis. The primary objectives were to determine disease-free survival (DFS) and overall survival (OS) for patients treated with LMWH. Results A total of 38 patients in the LMWH negative group and 44 patients in the LMWH positive group were included in the study. The median OS was 11.2 months for the enoxaparin recipients and 12.7 months for the non-enoxaparin group (p = 0.4). The median DFS was 9.3 months with CRT alone and 10.0 months with CRT plus enoxaparin (p = 0.9). The one-year OS rates were 47% and 34% for groups treated with CRT and enoxaparin plus CRT, respectively, while the two-year OS rates were 23% and 21%, respectively. No significant difference was noted between the two groups in terms of grade 3–4 hematologic toxicity and mucositis (p = 0.3). Conclusions This study did not demonstrate improvements in survival for patients with NSCLC treated with enoxaparin. LMWHs positive contribution is still controversial.

Larinks kanserli hastada beyin sapı ve bazal ganglion tutulumu ile birlikte metoklopramidin indüklediği parkinsonizm

Parkinsonism and basal ganglion involvement due to antiemetic drugs, such as metoclopramide, is rarely encountered. However, bilateral basal ganglia and brain stem involvement has not yet been reported in patients with drug-induced Parkinsonism. A 52-year-old male patient with laryngeal carcinoma was treated with docetaxel, cisplatin, and 5-fluorouracil (DCF) chemotherapy. Because of severe nausea and vomiting 15 days after the first course of chemotherapy, meto clopramide was administered. Parkinsonism symptoms were observed on the 6th day of metoclopramide therapy. Cerebral MRI revealed bilateral basal ganglia and brain stem involvement. Metoclopramide therapy was promptly discontinued and oral biperiden was commenced. Parkinsonism findings almost completely improved on his control examination performed after one month. He was not given metoclopramide during further chemotherapy courses. Cerebral MRI taken after three months revealed that the lesions have completely relieved. This is an extremely rare case of metoclopramide-induced parkinsonism together with brain stem and basal ganglion involvement in a patient with laryngeal carcinoma treated by chemotherapy. The clinical and radiological improvement was observed with the cessation of the causative drug and biperiden therapy. J Clin Exp Invest 2012; 3(4): 536-538