Publications by authors named "Faysal Dane"

110 Publications

A Phase II Study of the Combination of Oxaliplatin, Capecitabine, and Trastuzumab and Chemoradiotherapy in the Adjuvant Setting in Operated Patients With HER2-positive Gastric or Gastroesophageal Junction Cancer (TOXAG Study): A Turkish Oncology Group Study.

Am J Clin Oncol 2021 May 12. Epub 2021 May 12.

Department of Medical Oncology, Acibadem Adana Hospital Departments of Radiation Medical Oncology, Baskent University, Adana Department of Medical Oncology, Hacettepe University Department of Medical Oncology, Dr. A.Y. Ankara Oncology Training and Research Hospital Department of Medical Oncology, Gazi University Department of Medical Oncology, Medical Park Ankara Hospital Department of Medical Oncology, Ankara Yildirim Beyazit University, Ankara Department of Medical Oncology, Marmara University Department of Medical Oncology, Ethica Incirli Hospital Roche Pharmaceuticals Department of Medical Pharmacology, Bahcesehir University School of Medicine Department of Biostatistics and Medical Informatics, Koc University/MedStats Consulting, Istanbul Department of Medical Oncology, Necmettin Erbakan University Meram School of Medicine, Konya Department of Medical Oncology, Ege University, Izmir, Turkey.

Background: Trastuzumab prolonged the overall survival in patients with advanced gastric cancer with human epidermal growth factor receptor 2 (HER2) overexpression in combination with chemotherapy. In this phase II open-label prospective study, the tolerability and safety of trastuzumab with chemotherapy, and chemoradiotherapy for curatively resected patients with HER2-positive gastric carcinoma was investigated.

Methods: The patients with HER2-positive gastric, or gastroesophageal junction adenocarcinoma, after gastrectomy plus D2 dissection, were included. They received 3 cycles of oxaliplatin (100 mg/m2 intravenously day 1) plus capecitabine (850 mg/m2 orally days 1 to 14), trastuzumab (8 mg/kg intravenously day 1 in cycle 1, 6 mg/kg thereafter) every 21 days, followed by chemoradiotherapy. Trastuzumab was given for 1 year.

Results: Of the 212 patients screened, 35 were eligible, and 34 were treated. The median age was 56 years (minimum to maximum: 35 to 75 y), male patients constituted 73.5% (n=25), and 33 (97.1%) had gastric adenocarcinoma. R0 resection was performed in 30 (88.2%). The majority (26, 61.7%) were in stage III disease. Most of the adverse events were grade I/II, the most frequent grade III side effects were nausea (3, 8.8%), vomiting (3, 8.8%), diarrhea (2, 5.9%), and weight loss (n=2, 5.9%). Two patients died during the first 3 cycles of chemotherapy and chemoradiotherapy; 1 secondary to pulmonary thromboembolism, and the other due to cerebral ischemia. After excluding 2 with early progression and 1 consent withdrawal, of the remaining 31 patients, 28 (90.3%) were able to complete the chemotherapy and chemoradiotherapy part of the trial. After the 25 months follow-up period, 21 patients (61.8%) were alive. Overall survival at 12 and 24 months was 75.0% and 58.0%, while disease-free survival at 12 and 24 months was 65.7% and 55.0%, respectively.

Conclusions: Trastuzumab in combination with capecitabine, oxaliplatin following chemoradiotherapy as the adjuvant therapy for gastric or gastroesophageal junction adenocarcinoma was considered as safe and tolerable. The frequency of HER2 overexpression in curatively resected patients is comparable to that in patients with metastatic disease (trial registration: clinicaltrials.gov the identifier: NCT01748773, December 13, 2012, https://clinicaltrials.gov/ct2/show/NCT01748773).
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http://dx.doi.org/10.1097/COC.0000000000000825DOI Listing
May 2021

The comparison of FOLFOX regimens with different doses of 5-FU for the adjuvant treatment of colorectal cancer: a multicenter study.

Int J Colorectal Dis 2021 Jun 14;36(6):1311-1319. Epub 2021 Feb 14.

Department of Medical Oncology, Dicle University Faculty of Medicine, Diyarbakır, Turkey.

Purpose: We aim to compare the efficiency and toxicity of three different 5-fluorouracil (5-FU) administration types in 5-FU, leucovorin, and oxaliplatin (FOLFOX) combination treatment for adjuvant therapy in colorectal cancer (CRC).

Methods: Five hundred and seventy patients with stage III colorectal carcinoma who received different FOLFOX regimens after curative resection were included. Patients were divided into three groups as FOLFOX-4, modified FOLFOX-6 (mFOLFOX-6), and mFOLFOX-4 for comparison of toxicity and disease-free survival (DFS) and overall survival (OS) times.

Results: Three-year DFS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 65%, 72%, and 72%, respectively. Five-year OS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 69%, 75%, and 67%, respectively. There was no statistically significant difference between the three treatment groups in terms of DFS and OS (p = 0.079, and p = 0.147, respectively). Among grade 1-2 adverse events (AE), thrombocytopenia, neuropathy, and stomatitis were more common in the mFOLFOX-6-treated group. The frequency of grade 1-2 nausea and vomiting were similar in mFOLFOX-6 (36.3% and 24%, respectively) and mFOLFOX-4 (32.4% and 24.7%, respectively) groups but were higher than that in the FOLFOX-4 (19.5% and 11.3%, respectively) group. Among the most common grade 3-4 AE, neutropenia (53.4%, 9%, and 13.5%, respectively) and diarrhea (10.5%, 2.2%, and 2.4, respectively) were more common in FOLFOX-4. The rate of anemia and febrile neutropenia was similar in treatment groups (p = 0.063, and p = 0.210, respectively).

Conclusion: In the adjuvant treatment of stage III CRC patients, three different 5-FU administration types in FOLFOX combination treatment can be used with similar efficiency and manageable toxicity.
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http://dx.doi.org/10.1007/s00384-021-03888-9DOI Listing
June 2021

Impact of prognostic nutritional index on survival in recurrent glioblastoma.

Neurocirugia (Astur : Engl Ed) 2021 Jan 13. Epub 2021 Jan 13.

Department of Internal Medicine Division of Medical Oncology, Marmara University School of Medicine, Marmara University Pendik Education and Research Hospital, Istanbul, Turkey.

Background: Primary brain tumors are relatively rare malignancy, with high-grade gliomas (glioblastoma multiforme and anaplastic gliomas) are the most common types. We aimed to evaluate the prognostic value of Prognostic Nutritional Index (PNI), which is calculated by lymphocyte count and albumin, in recurrent glioblastoma patients treated with systemic treatment.

Methods: Data of 64 patients with recurrent glioblastoma who received systemic treatment and followed in our clinic between 2012 and 2018 was retrospectively collected and analyzed. PNI was calculated as: [(10×serum albumin (g/dL))+(0.005×total lymphocyte count)]. Patients were categorized according to the median PNI value. We investigated the prognostic role of PNI groups, and survival outcomes.

Results: Median value of PNI was 45.7, and median follow-up duration was 9 months (1-68 months). Median overall survival (OS) was 7.9 months (95%CI: 5.5-10.4). Median OS was significantly longer in patients with PNI>45.7 compared to patients with PNI≤45.7 (13.9 months (95%CI: 10.5-17.4), and 4.6 months (95%CI: 2.5-6.8), p<0.001, respectively). In multivariate analysis, PNI was found to be an independent prognostic factor for OS [HR:0.41 (95%CI:0.22-0.74), p=0.03)].

Conclusion: In our study, the PNI was found to be an independent prognostic biomarker in patients with recurrent glioblastoma, but further prospective trials are necessary to validate its prognostic role.
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http://dx.doi.org/10.1016/j.neucir.2020.11.005DOI Listing
January 2021

Rechallenge with dabrafenib plus trametinib in anaplastic thyroid cancer: A case report and review of literature.

Curr Probl Cancer 2021 Apr 22;45(2):100668. Epub 2020 Oct 22.

Marmara University School of Medicine, Department of Internal Medicine, Division of Medical Oncology, Istanbul, Turkey.

Introduction: Anaplastic thyroid carcinoma (ATC) is a highly aggressive, undifferentiated rare tumor. Median overall survival is usually between 8 and10 months, with a 1-year survival rate of 20%. Conventional anthracycline based chemotherapy regimens demonstrate low response rates with short duration. Novel therapeutic agents including BRAF and MEK inhibitors based on the molecular landscape of ATC have been investigated.

Case Presentation: We herein report the rechallenge of a 52-year-old ATC patient with BRAF V600E mutation with dabrafenib plus trametinib. She presented with recurrent and progressive disease despite surgery, radiation therapy, 3 different chemotherapy regimens, and combination of dabrafenib-trametinib in different settings. She was rechallenged with dabrafenib-trametinib, and had a good response.

Conclusion: To our knowledge, this is the first ATC case who responded to dabrafenib-trametinib rechallenge, reported in the literature. We want to emphasize that combination of dabrafenib and trametinib might be a good choice for resistant locoregional and metastatic ATC patients with BRAF V600E mutation, particularly in whom rapid clinical response is urgently needed. Moreover, rechallenge with this combination should be kept in mind in selected cases.
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http://dx.doi.org/10.1016/j.currproblcancer.2020.100668DOI Listing
April 2021

Tyrosine kinase inhibitors in the treatment of metastatic renal cell cancer patients with early cytokine intolerance: TURCOS, a Turkish national, prospective observational study.

J Oncol Pharm Pract 2020 Oct 13:1078155220963535. Epub 2020 Oct 13.

Department of Preventive Oncology, Hacettepe University Institute of Oncology, Ankara, Turkey.

Objective: Cytokines have been the mainstay of treatment in metastatic renal cell cancer (mRCC) for decades before the introduction of tyrosine kinase inhibitors (TKIs), which dramatically changed the therapeutic landscape in these patients. This observational study was designed to evaluate use of TKIs in the treatment of cytokine-intolerant mRCC patients.

Methods: A total of 151 cytokine-intolerant mRCC patients who were treated with TKIs (sunitinib, pazopanib and sorafenib) were enrolled in this prospective, non-interventional, multi-center observational study at 16 oncology centers across Turkey. Mean (SD) age was 61.3 (11.1) years and 74.8% were males. Data on duration of TKI treatment was the primary outcome measure. Additionally, overall response rate (ORR), progression free survival (PFS), overall survival (OS) and safety data were recorded.

Results: Median duration of treatment was 8.2 months at a median follow up of 17.9 months. ORR and disease control rate were 12.5% and 70.8%, respectively. Median PFS and OS were 7.5 months (95%CI: 6.4-10.4) and 27.3 months (95%CI: 17.6-27.3) with no significant difference among three TKI agents in terms of treatment duration, ORR, PFS and OS. The most common adverse events excluding progression-which was the protocol requirement were diarrhea (13.6%), asthenia (13.6%) and hand-foot syndrome (12.6%). Dose modifications were required in 30.5% of the patients and 15% discontinued TKIs because of toxicity.

Conclusions: Our findings confirm the efficacy and safety profile of TKIs in the first-line treatment of mRCC patients intolerant to cytokine treatment. There was no significant difference among three TKI agents in terms of treatment duration, ORR, PFS and OS. TURCOS ClinicalTrials.gov Identifier: NCT01585974. Registered April 25, 2012.
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http://dx.doi.org/10.1177/1078155220963535DOI Listing
October 2020

Is insulin resistance a predictor for complete response in breast cancer patients who underwent neoadjuvant treatment?

World J Surg Oncol 2020 Sep 9;18(1):242. Epub 2020 Sep 9.

Division of Medical Oncology, Marmara University School of Medicine, Marmara University Pendik Education and Research Hospital, Fevzi Cakmak Mah, Muhsin Yazicioglu C, No 10, Ust Kaynarca, 34890, Istanbul, Turkey.

Purpose: Neoadjuvant chemotherapy is the standard front-line treatment modality in locally advanced breast cancer. Achieving pathological complete response (pCR) is a significant prognostic factor for prolonged disease-free and overall survival. Insulin resistance is defined as a pathological condition in which insulin effect is impaired in peripheral target tissues such as the skeletal muscle, liver, and adipose tissue. The relationship between breast cancer and insulin resistance is controversial. In this study, our aim is to evaluate the role of insulin resistance, body mass index (BMI), metabolic syndrome, and inflammation markers to predict complete response in breast cancer patients who underwent neoadjuvant treatment.

Methods: Data from 55 locally advanced non-diabetic breast cancer patients, treated with neoadjuvant chemotherapy between 2015 and 2017, were retrospectively evaluated. Homeostatic model assessment, IR = insulin resistance (HOMA-IR) was calculated by using the obtained insulin and fasting blood glucose values before neoadjuvant chemotherapy (fasting insulin × fasting glucose/405). We considered a cut-off of 2.5 for insulin resistance. The systemic inflammatory index (SII), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were calculated.

Results: Twenty-five patients had no insulin resistance. The most common pathologic subtype (56%) was hormone receptor (HR) positive and human epidermal growth factor receptor-2 (Her-2)-negative invasive ductal carcinoma. Sixteen (29%) patients had a pathological complete response (pCR). We found that the probability of pCR in patients with insulin resistance was 4.7 times lower than that in patients without insulin resistance [OR: 4.7 (95%CI 1.7-17.2), p = 0.01].

Conclusion: Our results revealed that insulin resistance may have a negative effect on pathological complete response (pCR) following neoadjuvant therapy particularly with hormone-positive and Her-2-negative cases of non-diabetic breast cancer.
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http://dx.doi.org/10.1186/s12957-020-02019-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488234PMC
September 2020

Differences in PET/CT standardized uptake values involvement and survival compared to histologic subtypes of lung adenocarcinoma.

Tumori 2021 Jun 2;107(3):231-237. Epub 2020 Sep 2.

Department of Medical Oncology, Faculty of Medicine, Marmara University, Istanbul, Turkey.

Purpose: Lung adenocarcinoma is histologically diverse but has distinct histologic growth patterns. There is no consensus on the clinical benefit of this histologic model. We aimed to evaluate the differences in the distribution of the preoperative primary tumor positron emission tomography (PET)/computed tomography (CT) standardized uptake values (SUVs) and survival in the lung adenocarcinoma subtypes.

Methods: We retrospectively evaluated the data of 107 patients with resected lung adenocarcinoma who had preoperative PET/CT between 2005 and 2017 in a single center. Patients had lepidic, acinar, papillary, micropapillary, and solid histologic subtypes. We compared fluorodeoxyglucose SUVs and survival data of histologic subtypes.

Results: The median age of the patients was 62 years (40-75), 76.4% were male, the median SUVmax was 9.4 (1-36.7), and the median follow-up time was 29 months (3-135 months). The median overall survival (OS) was 71 months and the median progression-free survival (PFS) was 33 months. SUVmax was significantly different in histologic subtypes: values for papillary, micropapillary, solid, acinar, and lepidic subtypes were 9.7, 8, 12, 9.1, and 3.9, respectively ( = 0.000). Solid predominant adenocarcinoma had significantly higher SUVmax than the other subtypes ( = 0.001). Lepidic predominant adenocarcinoma had significantly lower SUVmax than the other subtypes ( = 0.000). There was no significant difference in OS between histologic subtypes ( = 0.66), but PFS was significantly different between the groups ( = 0.017), and the solid subtype had a shorter PFS than the other histologic subtypes.

Conclusion: Lung adenocarcinoma consists of a diverse group of diseases. Different SUVmax values are seen in different histologic subtypes of nonmetastatic lung adenocarcinoma. Solid predominant types have high SUVmax values while lepidic predominant types have lower SUVmax values. The solid subtype had a shorter PFS than the other histologic subtypes.
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http://dx.doi.org/10.1177/0300891620950475DOI Listing
June 2021

Prognostic value of modified Glasgow prognostic score in recurrent high-grade glial tumors treated with systemic treatment.

Clin Neurol Neurosurg 2020 09 30;196:105976. Epub 2020 May 30.

Department of Medical Oncology, Faculty of Medicine, Marmara University, Istanbul, Turkey.

Objectives: Malignant high-grade gliomas are the most common and aggressive type of primary brain tumor. We aimed to evaluate the prognostic value of modified Glasgow Prognostic Score (mGPS), which is combination of C-reactive protein (CRP) and albumin, in recurrent high-grade glioma patients treated with systemic treatment.

Patients And Methods: Data of 85 patients with recurrent high-grade glioma who received systemic treatment and followed in our clinic between 2012 and 2018 was retrospectively collected and analyzed. Patients were grouped according to mGPS criteria: mGPS-0: CRP < 10 mg/L and albumin >3.5 g/dL; mGPS-1: CRP < 10 mg/L and albumin <3.5 g/dL or CRP > 10 mg/L and albumin >3.5 g/dL; and mGPS-2: CRP > 10 mg/L and albumin <3.5 mg/L. We investigated the prognostic role of mGPS groups, mutations and survival outcomes.

Results: There were 42 (49.4 %), 25 (29.6 %), and 18 (21 %) patients in mGPS-0, mGPS-1, and mGPS-2 groups, respectively. Median follow-up duration was 10 months (1-70 months). Median OS was 8.1 months. According to mGPS-0, -1 and -2; median OS was 13.8 months, 7.3 months and 3.6 months respectively (p = 0.003). mGPS, ATRX and IDH-1 mutation status, and ECOG PS were found to be independent prognostic factors for OS.

Conclusion: In our study, mGPS was found to be an independent prognostic factor in patients with recurrent high-grade gliomas. If validated, mGPS can be used as an objective, easily calculated, cheap, and readily available prognostic model in routine practice.
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http://dx.doi.org/10.1016/j.clineuro.2020.105976DOI Listing
September 2020

QT interval prolongation related to afatinib treatment in a patient with metastatic non-small-cell lung cancer.

Curr Probl Cancer 2020 12 27;44(6):100594. Epub 2020 May 27.

Marmara University School of Medicine, Department of Internal Medicine, Division of Medical Oncology, Istanbul, Turkey.

Afatinib improves survival in metastatic non-small-cell lung cancer driven by activating epidermal growth factor receptor mutations. QT interval prolongation is a possible side effect of targeted anticancer drugs, but this has not been reported before with afatinib. We report a case of metastatic pulmonary adenocarcinoma with epidermal growth factor receptor exon 19 deletion who was treated with first-line afatinib. The patient was started on afatinib with a total dose of 40 mg/day and experienced grade 3 (>500 ms) QT interval prolongation in the seventh week. Dose was interrupted and then reduced to 30 mg/day after the event repeated. QT prolongation occurred only once with the reduced dose and radiologic oligoprogression was detected. Local therapy was performed and afatinib was continued as 30 mg/day. To the best of our knowledge, this case marks the first QT interval prolongation associated with afatinib. It is prudent to perform a baseline cardiologic evaluation and electrocardiogram monitoring in non-small cell lung cancer patients treated with this drug.
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http://dx.doi.org/10.1016/j.currproblcancer.2020.100594DOI Listing
December 2020

A rare case of gastric cancer with bilateral breast metastasis during pregnancy.

J Oncol Pharm Pract 2021 Jan 23;27(1):220-226. Epub 2020 May 23.

Department of Internal Medicine, Division of Medical Oncology, Marmara University Faculty of Medicine, Istanbul, Turkey.

Background: Gastric cancer is rare during pregnancy and often diagnosed at a later stage due to overlapping symptoms of pregnancy. Breast metastasis of gastric cancer is another uncommon entity. We present a rare case of breast metastasis of gastric cancer during pregnancy.

Case Report: A 26-year-old female was diagnosed with gastric cancer at 14 weeks of gestation and underwent total gastrectomy. She rejected adjuvant chemotherapy and continued pregnancy without any follow-up. Cancer recurred in bilateral breasts at 34th week of gestation mimicking primary inflammatory breast cancer.

Management And Outcome: It was difficult to diagnose breast metastasis during pregnancy because of overlapping pregnancy symptoms. Following an unresponsive period to antibiotherapy, a fine needle biopsy on breast was performed and signet cell adenocarcinoma metastasis was determined. We started chemotherapy after delivery. There was a near complete response after first line of chemotherapy. Unfortunately, cancer was relapsed within three months and we started second-line chemotherapy.

Discussion: To our knowledge, this is the fourth case reported in medical literature of gastric cancer presented with breast metastasis during pregnancy. We will try to draw attention to diagnosis, treatment and different presentation of gastric cancer during pregnancy with review of the literature.
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http://dx.doi.org/10.1177/1078155220925156DOI Listing
January 2021

Pazopanib for metastatic soft-tissue sarcoma: A multicenter retrospective study.

J Oncol Pharm Pract 2021 Apr 16;27(3):541-546. Epub 2020 May 16.

Department of Medical Oncology, Pendik Training and Research Hospital, Marmara University, Turkey.

Purpose: Soft tissue sarcomas are associated with a poor prognosis and low chemotherapeutic efficiency. Pazopanib is an orally available multi-tyrosine kinase inhibitor that was explored in patients with non-adipocytic advanced soft tissue sarcomas. The aim of this retrospective study was to evaluate the real life data of single-agent pazopanib efficacy and safety for soft tissue sarcomas in the Turkish population.

Materials And Methods: We evaluated a total of 103 patients (41 males, 62 females) who received pazopanib for advanced non-adipocytic soft tissue sarcomas diagnosis in eight centers of Turkey, retrospectively. The pazopanib dose was 800 mg once daily. Progression-free survival, overall survival, and adverse events were analyzed.

Results: The median age was 50 years (range, 38-58). Majority of the patients had leimyosarcoma (41%). Median progression-free survival was 4.3 months, and the median overall survival was 10.1 months. The main common toxicities were fatigue, anorexia, weight loss, nausea, hypertension, and grade ≥3 toxicities were fatigue, anorexia, weight loss, and liver disorder.

Conclusion: Pazopanib is an efficient and tolerable agent and is well tolerated in good performance status patients with relapsed, advanced non-adipocytic soft tissue sarcomas.
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http://dx.doi.org/10.1177/1078155220924075DOI Listing
April 2021

Prognostic factors in progressive high-grade glial tumors treated with systemic approach: A single center experience.

J Oncol Pharm Pract 2021 Mar 29;27(2):329-339. Epub 2020 Apr 29.

Division of Medical Oncology, Department of Internal Medicine, Marmara University Faculty of Medicine, Istanbul, Turkey.

Purpose: Malignant high-grade gliomas are the most common and aggressive type of primary brain tumor, and the prognosis is generally extremely poor. In this retrospective study, we analyzed the outcome of systemic treatment in recurrent high-grade glioma patients and the impact of prognostic factors on survivals.

Methods: Data from 114 patients with recurrent high-grade glioma who received systemic treatment and followed in our clinic between 2012 and 2018 were retrospectively analyzed. Eastern Cooperative Oncology Group (ECOG) performance status, age, gender, histology, type of surgical resection, side effects after systemic treatment (deep vein thrombosis, hypertension, proteinuria), IDH1 and alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutation status were investigated as prognostic factors for progression-free survival and overall survival.

Results: At the time of diagnosis, the median age was 48 (17-77) and 68% of the patients were male. Most common pathologic subtype was glioblastoma multiforme (68%). Median follow-up duration was 9.1 months (1-68 months). Median progression-free survival and overall survival were 6.2 months and 8 months, respectively. In multivariate analysis, ECOG PS, deep venous thrombosis and the presence of ATRX and IDH1 mutation were found to be independent prognostic factors for progression-free survival (p < 0.05) and, ECOG PS, the presence of ATRX and IDH1 mutation for overall survival (p < 0.05).

Conclusion: Our study is real life data and the median progression-free survival and overall survival rates are similar to the literature. We have found ECOG PS, presence of ATRX and IDH1 mutation to be independent prognostic factors for both progression-free survival and overall survival.
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http://dx.doi.org/10.1177/1078155220920684DOI Listing
March 2021

Modified Glasgow Prognostic Score, Prognostic Nutritional Index and ECOG Performance Score Predicts Survival Better than Sarcopenia, Cachexia and Some Inflammatory Indices in Metastatic Gastric Cancer.

Nutr Cancer 2021 9;73(2):230-238. Epub 2020 Apr 9.

Division of Medical Oncology, Marmara University School of Medicine, Istanbul, Turkey.

Gastric carcinoma (GC) patients usually present with locally advanced or metastatic disease; therefore treatment aim is mainly palliation. In this study our purpose is to analyze the prognostic values of the sarcopenia index (SI), cachexia index (CIn) and other inflammatory indexes (advanced lung cancer inflammation index [ALI], modified Glasgow Prognostic Score [mGPS], prognostic index [PI], prognostic nutritional index [PNI] and neutrophil-to-lymphocyte ratio [NLR]) in metastatic GC patients. Data from the files of metastatic GC patients, who applied to Medical Oncology outpatient clinic in Marmara University Pendik Education and Research Hospital between January 2011 and June 2016, were retrospectively reviewed. Five hundred seventy patients with gastric cancer were detected. Exclusion criteria were the inability to reach the patient surveys for prognostic index calculations, the presence of additional comorbidities to affect the laboratory parameters, and the absence of metastatic disease. Finally, 87 of these patients were included in this study. For SI calculation L3 level muscle area was measured from patients' computed tomography (CT) by a radiologist. SI reference value was obtained from western-EGWSOP (The European Working Group on Sarcopenia in Older People) and eastern (Harada Y, et al.) sources separately, as Turkey doesn't have a reference value for SI. NLR cutoff value was accepted as the median value of patients' NLR measurements. Statistical analysis was conducted using SPSS. Kaplan-Meier and Cox regression models were used to assess independent prognostic factors. The area under the curve was used to compare the prognostic value of indexes. The median length of follow-up of 87 patients was nine months (1-64 mo,/s), and 78 patients died during follow-up. Fifty-nine patients were male (63%), and the median age was 62 (range, 23-88). According to univariate analysis high mGPS and PI score, PNI level <45, NLR level ≥ 3.41, ALI level <18, CI level under 35, SI (Harada Y, et al) ≤44.5 for males and ≤36.5 for females, ECOG score ≥ 2, weight loss more than 10% during last 6 mo, BMI under 24 were poor prognostic factors. Age, gender, having multiple organ metastasis, history of gastric surgery, positivity C-erb-B2, SI (EGWSOP) ≤52.4 for males, and ≤38.4 for females did not have any impact on survival. According to multivariate analysis, high mGPS (score 2) (HR 2,494, 95% CI 1.25-4 .94,  = 0.02), PNI (score 1) (HR 4.2, 95% CI 1.73-10.1,  < 0.001) and ECOG score (≥2) (HR 1.541, 95% CI 1,089-4,214,  = 0.004) have been found to be independent prognostic factors which are determining the survival. mGPS was found to be more valuable than other indexes for predicting mortality by measuring the AUC with ROC analysis. In our study, mGPS, PNI and ECOG score were independent indicators for shorter survival in metastatic gastric cancer patients. mGPS and PNI, which can be done by using only serum CRP, albumin level and complete blood count, might be inexpensive, practical and beneficial to use in routine clinical practice to determine survival.
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http://dx.doi.org/10.1080/01635581.2020.1749290DOI Listing
April 2020

Long-term neuromusculoskeletal side effects and quality of life in nasopharyngeal cancer patients receiving radiochemotherapy.

Eur Arch Otorhinolaryngol 2020 Aug 31;277(8):2325-2333. Epub 2020 Mar 31.

School of Medicine, Department of Radiation Oncology, Marmara University, Istanbul, Turkey.

Aim: In this study, we aimed to evaluate the neuromusculoskeletal late side effects and their impact on the quality of life of patients with nasopharyngeal carcinoma treated with radiochemotherapy.

Patients And Methods: Twenty-seven patients were included. The mean follow-up was 61 months (range, 18-111 months). The median external radiotherapy dose applied to the nasopharynx and primary tumor was 70 Gy (range, 61-73 Gy). The mean dose received by the temporomandibular joint in the dose-volume histograms of these patients was 60.7 Gy. The maximal doses of the muscles responsible for cervical motion in different ranges were greater than 60 Gy, and the mean doses were greater than 40 Gy in the muscle groups, except for the extensor muscles.

Results: Two patients had brachial plexus involvement, while 89% of the patients had restriction in flexion and extension movements. Of the patients, 52% had trismus. There was a significant correlation between extension restriction and general heath score and the physical subscale of the quality-of-life questionnaire (p = 0.01). There was also a correlation between trismus and pain killer usage (p = 0.004).

Conclusion: This is the first study to analyze long-term muscle and nerve toxicity and their correlation between doses in nasopharyngeal cancer patients following radiochemotherapy. Despite the advances in radiotherapy techniques, it is necessary to pay attention to the doses of the nerves and muscles for late effects.
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http://dx.doi.org/10.1007/s00405-020-05932-wDOI Listing
August 2020

Quality of life study of patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma treated with gemcitabine+nab-paclitaxel versus gemcitabine alone: AX-PANC-SY001, a randomized phase-2 study.

BMC Cancer 2020 Mar 30;20(1):259. Epub 2020 Mar 30.

Hacettepe University Cancer Institute, Ankara, Turkey.

Background: Combination of gemcitabine and nab-paclitaxel has superior clinical efficacy than gemcitabine alone. Nevertheless, health-related quality of life. (QoL) associated with this combination therapy when administered at first-line in advanced pancreatic adenocarcinoma is unknown.

Methods: A total of 125 patients were randomized to combination therapy (1000 mg/m2 gemcitabine + 125 mg/m2 nab-paclitaxel) and single-agent gemcitabine (1000 mg/m2) arms to take treatment weekly for 7 of 8 weeks, and following 3 of 4 weeks, until progression or severe toxicity. Primary endpoints were three-months of definitive deterioration free percent of patients, and QoL.

Results: Overall QoL analyses showed that 34 and 58.3% of cases in gemcitabine and gemcitabine+nab-P arms had no deterioration in 3rd month QoL scores (p = 0.018). These proportions were 27.3 and 36.6% in 6 month assessments, respectively (p = 0.357). Median overall survivals in combination and single-agent arms were 9.92 months and 5.95 months, respectively (HR: 0.64, 95% CI: 0.42-0.86, p = 0.038). Median progression free survivals in these treatment arms were 6.28 and 3.22 months, respectively (HR: 0.58, 95% CI: 0.39-0.87, p = 0.008). Median time-to-deterioration were 5.36 vs 3.68 months, and objective response rates were 37.1% vs 23.7% (p = 0.009), respectively in combination and single-agent arms.

Conclusions: Combination therapy with gemcitabine + nab-paclitaxel had better overall and progression-free survival than gemcitabine alone. Also, combination therapy showed increased response rate without toxicity or deteriorated QoL. Combination treatment with gemcitabine and nab-paclitaxel may provide significant benefit for advanced pancreatic cancer.

Trial Registration: This study has been registered in ClinicalTrials.gov as NCT03807999 on January 8, 2019 (retrospectively registered).
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http://dx.doi.org/10.1186/s12885-020-06758-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106641PMC
March 2020

Safety and efficacy of regorafenib in patients with treatment-refractory metastatic colorectal cancer in Turkey: the single-arm, open-label REGARD study.

BMJ Open 2020 03 26;10(3):e027665. Epub 2020 Mar 26.

Division of Medical Oncology, Department of Internal Medicine, Marmara University Medical Faculty, Istanbul, Turkey.

Objectives: Regorafenib improved overall survival in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies in two randomised, phase III trials, but has not been evaluated in Turkey. REGARD evaluated the safety and efficacy of regorafenib in Turkish patients with treatment-refractory mCRC.

Design: Open-label, single-arm, phase IIIb study conducted between July 2013 and April 2015.

Setting: 11 tertiary centres in Turkey.

Participants: Eligible patients were adults with mCRC who had disease progression within 3 months after receiving their last dose of approved standard therapies and who had an Eastern Cooperative Oncology Group performance status ≤1. Patients were excluded if they had previously received regorafenib. Of 139 patients screened, 100 were treated and completed the study, and all 100 were analysed. Fifty-eight per cent were male.

Interventions: Patients received oral regorafenib, 160 mg once daily, for the first 3 weeks of each 4-week cycle until disease progression, death or unacceptable toxicity.

Primary And Secondary Outcome Measures: The primary endpoint was safety, assessed by incidence of treatment-emergent adverse events (TEAEs). Progression-free survival (PFS) per investigator was the primary efficacy endpoint. There were no secondary endpoints.

Results: The median treatment duration was 2.5 months (range 0.1 to 20.6). Ninety-six per cent of patients had at least one TEAE and 77% had a grade ≥3 TEAE. The most common grade ≥3 regorafenib-related TEAEs were hypophosphataemia (11%), fatigue (8%), hyperbilirubinaemia (6%), hand-foot skin reaction (5%), hypertension (5%), anorexia (5%) and increased alanine aminotransferase (5%). TEAEs led to dose reduction in 30% of patients. Regorafenib-related TEAEs led to treatment discontinuation in 17% of patients. Median PFS was 3.1 months (95% CI 2.9 to 3.8).

Conclusion: The regorafenib safety profile and PFS in REGARD were consistent with the results of previous trials of regorafenib in mCRC. Regorafenib is an option for patients in Turkey with treatment-refractory mCRC.

Trial Registration Number: NCT01853319, ClinicalTrials.gov.
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http://dx.doi.org/10.1136/bmjopen-2018-027665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170555PMC
March 2020

VEGF-VEGFR pathway seems to be the best target in hepatic epithelioid hemangioendothelioma: A case series with review of the literature.

Curr Probl Cancer 2020 10 14;44(5):100568. Epub 2020 Mar 14.

Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey.

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor originating from endothelial cells. Clinical aspect of the disease covers a wide spectrum from a low-grade tumor to a fatal cancer. Most common sites of EHE are reported as lung, liver and bone. Hepatic EHE (HEHE) is a clinical form with an incidence of less than 1 person in a million. Due to rarity of the disease, there is no standard therapy established. Surgery and liver transplantation still seem to be the best approach if possible. However, most of the patients present with unresectable or metastatic disease. Many conventional chemotherapeutic agents and antiangiogenic drugs have been reported previously in the literature with inconsistent outcomes. Here we report 4 cases of HEHE, who benefit distinctly from anti-VEGF treatments in different settings. While combination of paclitaxel and bevacizumab resulted in partial response in 3 patients, one of them also achieved long-term disease stabilization with bevacizumab maintenance with no adverse event. Two of the patients had clear benefit from pazopanib during the course of disease. One patient was treated with thalidomide for 18 months with stable disease, and is still being followed without any treatment. Although targeting VEGF-VEGFR pathway seems to be the best approach in HEHE, randomized studies are urgently needed to support these findings.
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http://dx.doi.org/10.1016/j.currproblcancer.2020.100568DOI Listing
October 2020

Impact of the Charlson Comorbidity Index on dose-limiting toxicity and survival in locally advanced and metastatic renal cell carcinoma patients treated with first-line sunitinib or pazopanib.

J Oncol Pharm Pract 2020 Jul 2;26(5):1147-1155. Epub 2019 Dec 2.

Department of Internal Medicine, Division of Medical Oncology, Marmara University School of Medicine, Istanbul, Turkey.

Background: Anti-angiogenic tyrosine kinase inhibitors, sunitinib and pazopanib, have proven efficacy in advanced renal cell carcinoma, with specific adverse events occurring during treatment process. Comorbidities can reflect functional status and have prognostic value in oncology patients. We aimed to assess the association of the Charlson Comorbidity Index with severe toxicities and mortality in renal cell carcinoma cases treated with front-line sunitinib or pazopanib.

Methods: Files of locally advanced and metastatic renal cell carcinoma patients who received first-line sunitinib or pazopanib were retrospectively examined. Charlson Comorbidity Index of each patient was calculated. Patients were also stratified into Memorial Sloan-Kettering Cancer Center risk groups. Predictors of dose-limiting toxicity were evaluated with binomial logistic regression analysis. Univariate and multivariate Cox regression models were utilized to determine prognostic factors for survival.

Results: The study included 102 patients, 64 were treated with first-line sunitinib and 38 with pazopanib. In 42 patients (41.9%), Charlson Comorbidity Index was 9 or more. Dose-limiting toxicities were significantly more frequent in Charlson Comorbidity Index ≥9 group (69% vs. 40%, p = 0.004), and Charlson Comorbidity Index independently predicted dose-limiting toxicity (Hazard ratio (HR) = 4.30, p = 0.002). After adjusting for other variables, a Charlson Comorbidity Index of ≥9 is also a significant prognostic factor for progression-free (HR = 1.76, p = 0.02) and overall survival (HR = 1.75, p = 0.03).

Conclusions: Charlson Comorbidity Index may be a valuable method to estimate prognosis and optimize therapy in patients with advanced renal cell carcinoma receiving first-line sunitinib or pazopanib.
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http://dx.doi.org/10.1177/1078155219890032DOI Listing
July 2020

Assessment of survival and prognostic factors in metastatic colorectal cancer patients treated with first-line bevacizumab-based therapy.

J BUON 2019 Jul-Aug;24(4):1494-1500

Marmara University School of Medicine, Department of Internal Medicine, Division of Medical Oncology, Istanbul, Turkey

Purpose: Colorectal cancer (CRC) is a significant cause of cancer mortality worldwide. Survival has improved with bevacizumab in metastatic CRC treatment. Our purpose was to analyse survival and prognostic factors in metastatic CRC patients treated with first-line bevacizumab-based treatment.

Methods: Files of CRC patients were examined retrospectively and 360 patients treated with first-line bevacizumab were included. Objective response rates (ORRs), median progression-free and overall survival (PFS and OS) of the patients were calculated. Survival was analyzed with the Kaplan-Meier method. Log-rank test and Cox regression model were used for univariate and multivariate analyses, respectively.

Results: Median age at diagnosis was 59.5 years. Of the patients 74.4% had initially stage IV disease. Median PFS was 8.5 months, median OS 25.3 months and ORR was 51.4%. ORRs, median PFS and OS of KRAS mutant and wild-type or unknown patients were statistically similar. In left-sided disease, median PFS and OS (9.6 and 27.1 months) were superior compared to right-sided disease (7.3 and 19.4 months) (p=0.005 and 0.02, respectively). Primary disease location, histopathologic grade, primary surgery and metastasectomy affected OS significantly. Histopathologic grade (hazard ratio=1.77, p=0.002) and metastasectomy (hazard ratio=0.48, p=0.001) were independent prognostic factors.

Conclusions: Our study confirmed that after bevacizumab-based treatment, KRAS status might not be a prognostic factor. We have also shown that left CRC have more favorable outcomes than right CRC in bevacizumab therapy. Additionally, even in metastatic setting histopathologic grade of the primary CRC together with metastasectomy are independent prognostic factors.
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March 2020

How long should we continue crizotinib in ALK translocation-positive inflammatory myofibroblastic tumors? Long-term complete response with crizotinib and review of the literature.

J Oncol Pharm Pract 2020 Jun 15;26(4):1011-1018. Epub 2019 Oct 15.

Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Marmara University, Istanbul, Turkey.

Introduction: Inflammatory myofibroblastic tumor is a rare disease which is typically seen in children and young adults. Approximately half of the inflammatory myofibroblastic tumors contain translocations that result in over-expression of anaplastic lymphoma kinase gene. Herein, we present two anaplastic lymphoma kinase-positive cases with long-term remission with crizotinib. We do not know how long these therapies need to be continued.

Case Reports: We present two cases of inflammatory myofibroblastic tumor treated with anaplastic lymphoma kinase inhibitor therapies: an 8-year-old Turkish boy and a 21-year-old Caucasian man.

Management And Outcome: Two cases, both with good tumor control under crizotinib, but one who progressed on drug holiday, responded again to the same drug, and had a very short period of response after restarting crizotinib.

Conclusion: A molecular-targeted drug (anaplastic lymphoma kinase inhibitor) was found to be extremely effective as selective therapy for inflammatory myofibroblastic tumor with anaplastic lymphoma kinase translocation. Here, we want to emphasize the continuation of this treatment after achieving a good response until progression or a major side effect.
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http://dx.doi.org/10.1177/1078155219879757DOI Listing
June 2020

A rare case of primary rectal choriocarcinoma and review of the literature.

J Oncol Pharm Pract 2020 Jun 23;26(4):989-994. Epub 2019 Sep 23.

Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey.

Introduction: Primary choriocarcinoma of the colon is an extremely rare neoplasm which has a poor prognosis. Only 18 cases have been previously reported in English medical literature. Here we present a case of primary rectal choriocarcinoma with a good response to chemotherapy and review the literature on this uncommon tumor.

Case Report: A 36-year-old woman presented with abdominal pain and vaginal bleeding. Abdominal magnetic resonance imaging revealed 6.9 × 5.3 × 6.4 cm hypervascular mass posterior to uterus very close to rectum. Beta-human chorionic gonadotropin (β-hCG) level was markedly elevated. Low anterior resection of the rectum with lymph node dissection and total abdominal hysterectomy with bilateral salpingo-oophorectomy were performed. Pathologic diagnosis was reported as colonic choriocarcinoma with a focal component of adenocarcinoma. Post-operative magnetic resonance imaging detected multiple metastatic lesions throughout the liver. The patient was treated with systemic chemotherapy using bleomycin, etoposide and cisplatin (BEP protocol). After three cycles, β-hCG level decreased to normal and magnetic resonance imaging showed regression of liver metastasis. However, the patient died of respiratory failure due to bleomycin toxicity and pneumonia accompanied by rapid disease progression.

Discussion: This is an extremely rare case of primary rectal choriocarcinoma. Due to poor prognosis of the disease, it seems very important to start prompt treatment to improve patient's survival.
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http://dx.doi.org/10.1177/1078155219875510DOI Listing
June 2020

Clinicopathologic and Prognostic Differences between Three Different Age Groups (Child/Adolescent, Young Adults, and Adults) of Colorectal Cancer Patients: A Multicentre Study.

Oncol Res Treat 2019 22;42(10):516-522. Epub 2019 Aug 22.

Department of Medical Oncology, Dicle University Faculty of Medicine, Diyarbakir, Turkey.

Background: Colorectal cancer (CRC) is a rare disease amongst children and adolescents. Previous studies have reported a number of differences between children/adolescents, young adults, and adult patients with CRC. However, none of these studies compared these age groups according to their clinicopathologic and prognostic characteristics. In the current study, we compare these three age groups.

Methods: A total of 173 (1.1% of 15,654 patients) young CRC patients (≤25 years) were included in the study. As a control group, 237 adult CRC patients (>25 years) were also included. Patients were divided into three age groups: child/adolescent (10-19 years), young adult (20-25 years), and adult (>25 years).

Results: Statistical differences amongst the three groups in terms of gender (p = 0.446), family history (p = 0.578), symptoms of presentation (p = 0.306), and interval between initiation of symptoms and diagnosis (p = 0.710) could not be demonstrated. Whilst abdominal pain (p < 0.001) and vomiting (p = 0.002) were less common in young adults than in other groups, rectal bleeding and changes in bowel habits were relatively less common in adolescents than in other groups. Rectal localisation (p = 0.035), mucinous adenocarcinoma (p < 0.001), and a poorly differentiated histologic subtype (p < 0.001) were less common in the adult group than in other groups. The percentage of patients with metastasis and sites of metastasis (e.g., peritoneum and lung) differed between groups. The median overall survival was 32.6 months in the adolescent group, 57.8 months in the young adult group and was not reached in the adult group (p = 0.022). The median event-free survival of the adolescent, young adult, and adult groups was 29.0, 29.9, and 61.6 months, respectively (p = 0.003).

Conclusions: CRC patients of different age groups present different clinicopathologic and prognostic characteristics. Clinicians should be aware of and manage the disease according to these differences.
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http://dx.doi.org/10.1159/000502120DOI Listing
February 2020

The efficacy and reliability of sequential adjuvant anthracycline-based chemotherapy and weekly paclitaxel regimen in human epidermal growth factor receptor 2 negative breast cancer: A retrospective analysis of a multicentre study.

J BUON 2019 May-Jun;24(3):1081-1086

Dicle University Faculty of Medicine, Department of Medical Oncology, Sur/Diyarbakir, Turkey.

Purpose: To analyze the reliability and the effectiveness of chemotherapy and prognostic factors for survival in patients with HER2 (human epidermal growth receptor 2) negative early-stage breast cancer treated with adjuvant sequential anthracycline-based chemotherapy and paclitaxel.

Methods: This analysis retrospectively evaluated the medical records of 756 HER2 negative early-stage breast cancer patients who received adjuvant sequential anthracycline-based chemotherapy and weekly paclitaxel in 15 medical oncology centers in Turkey between 2008-2015. Estrogen receptor (ER), progesterone receptor (PR),HER2,age,tumor size and grade,nodal status,perineural and lymphatic invasion,disease-free survival (DFS) and overall survival (OS) were analyzed.

Results: The median patient age was 50 years (22-82). Median follow up period was 46 months (13-82). The rates of recurrence and death detected in this period were 14.8% and 7.4%, respectively. Median OS and PFS were not reached in this period. Five-year DFS and OS rates were 87% and 89%, respectively. Age (OR:0.35,95%Cl 0.12-0.96, p=0.04), PR status (OR:0.44,95%Cl 0.18-1, p=0.05), lymphatic invasion (OR:2.6,95%Cl 0.97-7.4, p=0.05) were independent prognostic factors. Most common grade 3-4 toxicities were fatigue (6.7%), neutropenia (1.7%) and nausea (1.3%). Neutropenic fever developed in 1.8% of the patients and peripheral neuropathy in 16.9%. Dose reduction was necessary for 10% of the patients due to grade 3-4 toxicity, whereas postponement of chemotherapy was necessary for 7% of the patients.

Conclusions: This multicentric retrospective study confirmed that sequential adjuvant therapy with anthracycline-based chemotherapy and paclitaxel for HER2 negative breast cancer is an effective and reliable regimen.
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March 2020

Kras-mutation influences outcomes for palliative primary tumor resection in advanced colorectal cancer-a Turkish Oncology Group study.

Surg Oncol 2018 Sep 30;27(3):485-489. Epub 2018 May 30.

Department of Medical Oncology, NecmettinErbakan University, Meram Faculty of Medicine, Konya, Turkey. Electronic address:

Purpose: We aimed to investigate the prognostic effect of primary tumor resection (PTR) prior to bevacizumab-based treatments in unresectable metastatic colorectal cancer (mCRC).

Methods: We retrospectively collected 341 mCRC cases with unresectable metastases at diagnosis. PTR was performed in 210 cases (the surgery group) and the other patients (n = 131) were followed without PTR (the no-surgery group). All the patients were treated with bevacizumab combined chemotherapy regimens.

Results: The median progression free survival (PFS) of the surgery group was 10.4 months (95% CI: 8.9-11.9), which was significantly better than that of the no-surgery group (7.6 months, 95% CI: 6.4-8.8, P=0.000). The median overall survival (OS) of the surgery group was longer than that of the no-surgery group (27.4 months vs. 18.3 months, respectively, P=0.000). The median PFS and OS of the surgery group were 10.4 months and 28.2 months, which were significantly longer than that of the no-surgery group in Kras-mutant patients (7.8 months and 18.3 months; P=0.004, P=0.028, respectively). There was no difference in terms of PFS and OS between the surgery and the no-surgery groups in Kras-wild type patients.

Conclusion: Palliative PTR may improve the survival outcomes for unresectable mCRC patients. PTR may be preferred, particularly in Kras-mutant patients.
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http://dx.doi.org/10.1016/j.suronc.2018.05.032DOI Listing
September 2018

Chordoma: a case series and review of the literature.

J Med Case Rep 2018 Aug 27;12(1):239. Epub 2018 Aug 27.

Division of Medical Oncology, Department of Internal Medicine, Marmara University Faculty of Medicine, Istanbul, Turkey.

Background: Chordoma is a rare malignant tumor of the skull base and axial skeleton, with an incidence of less than 0.1/100,000 per year. Patients with advanced chordoma have a poor prognosis due to locoregional recurrence with infiltration and destruction of surrounding bone and soft tissue. Cytotoxic chemotherapy or other systemic therapies have not been proven to be effective for these diseases. Therefore, several molecularly targeted therapies have been proposed as potentially beneficial, including tyrosine kinase inhibitors such as imatinib, sorafenib, lapatinib, and others.

Case Presentation: We present three cases of advanced chordoma treated with molecular targeted therapies: a 52-year-old Caucasian man, a 72-year-old Caucasian woman, and a 38-year-old Caucasian woman.

Conclusions: Chordoma has few systemic treatment options and they have limited benefit. Randomized trials with large patient numbers are unfeasible in this rare disease. Targeted therapy might be a reasonable alternative treatment for chordoma. Still, new treatment strategies are needed for this rare disease.
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http://dx.doi.org/10.1186/s13256-018-1784-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109974PMC
August 2018

A national, multicenter, non-interventional, observational study on treatment patterns in patients with metastatic renal cell carcinoma in Turkey - NOTES study.

Onco Targets Ther 2018 5;11:1223-1228. Epub 2018 Mar 5.

Novartis Oncology, İstanbul, Turkey.

Introduction: The introduction of targeted therapies in renal cell carcinoma has significantly improved its prognosis and treatment outcomes in recent years. Such treatment options are targeted therapies of the vascular endothelial growth factor (VEGF) pathway and the mammalian target of the rapamycin pathway. With the use of tyrosine kinase inhibitors (TKIs) and mammalian target of the rapamycin inhibitors, overall survival has increased up to 2 years. In Turkey, due to applicable reimbursement conditions for patients with metastatic renal cell carcinoma (mRCC), interferon use is mandated as a first-line treatment, thus providing information on the use of everolimus only after initial interferon and second-line VEGF-targeted treatments such as VEGF-TKI.

Patients And Methods: To provide a first real-life data set in Turkey, we conducted a prospective, non-interventional, observational study and assessed the efficacy and safety of everolimus after two lines of treatment including interferon. A total of 100 patients with histologically confirmed mRCC were enrolled in the study from 11 centers between June 2012 and March 2014 (70 males and 30 females). Efficacy was assessed on the basis of progression-free survival and overall survival; safety of everolimus was assessed on the basis of adverse event occurrence.

Results: The study results showed that the median progression-free survival with everolimus treatment was 8.1 months (95% CI: 5.1-11.1) and the median overall survival was 17.6 months (95% CI: 10.1-25.1), thus indicating a better overall response based on survival durations than those from the randomized Phase III REnal Cell cancer treatment with Oral RAD001 given Daily study results (4.9 and 14.8 months, respectively).

Conclusion: The study showed that everolimus treatment is a safe and effective treatment option in the treatment of mRCC after VEGF-TKI, with an acceptable safety and tolerability profile in real-life settings.
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http://dx.doi.org/10.2147/OTT.S148917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843136PMC
March 2018

Effectiveness and Safety of LMWH Treatment in Patients With Cancer Diagnosed With Non-High-Risk Venous Thromboembolism: Turkish Observational Study (TREBECA).

Clin Appl Thromb Hemost 2018 Sep 18;24(6):973-979. Epub 2018 Feb 18.

15 Department of Medical Oncology, Pamukkale University Medical Faculty, Denizli, Turkey.

We compared the efficacy and safety of low-molecular-weight heparins (LMWHs) in patients with cancer who are at low risk of venous thromboembolism (VTE). Patients were treated by medical oncologists in Turkey at 15 sites, where they were enrolled and followed up for a period of 12 months. Due to the study design, there was no specific treatment protocol for LMWH. Primary end points were efficacy and the time to change in VTE status. Of the included 250 patients, 239 (95.6%), 176 (70.4%), 130 (52.0%), and 91 (36.4%) completed their day 15, month 3, month 6, and month 12 visits, respectively. Number of patients treated with enoxaparin, bemiparin, and tinzaparin were 133, 112, and 5, respectively. Anticoagulant therapy provoked thrombus resolution in 1.2% and 12.7% of patients using enoxaparin and bemiparin, respectively ( P = .004). Thrombus resolution was observed in 81 more patients at month 3 visit. This ratio was 35 (40.2%) of 87 and 46 (54.1%) of 85 patients administered enoxaparin and bemiparin at the third visit, respectively ( P = .038). Thrombus resolution was observed in 21 more patients during month 6 visit. This ratio was 5 (7.7%) of 65 and 15 (23.4%) of 64 patients administered enoxaparin and bemiparin at the fourth visit, respectively ( P = .022). The LMWH was discontinued in only 2 patients due to gastrointestinal bleeding. This pioneering study shows bemiparin is more effective than enoxaparin in thrombosis resolution and has a similar tolerability profile.
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http://dx.doi.org/10.1177/1076029617753538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714721PMC
September 2018

Biosimilar filgrastim vs filgrastim: a multicenter nationwide observational bioequivalence study in patients with chemotherapy-induced neutropenia.

Onco Targets Ther 2018 18;11:419-426. Epub 2018 Jan 18.

Department of Medical Oncology, Atatürk University Faculty of Medicine, Erzurum, Turkey.

Background: We studied the comparative effectiveness of biosimilar filgrastim vs original filgrastim in patients with chemotherapy-induced neutropenia.

Patients And Methods: This multicenter, observational study was conducted at 14 centers. The study included 337 patients experiencing neutropenia under chemotherapy. Patients were given either filgrastim 30 MIU or 48 MIU (Neupogen) or biosimilar filgrastim 30 MIU (Leucostim). Data regarding age, chemotherapeutic agents used, number of chemotherapy courses, previous diagnosis of neutropenia, neutrophil count of patients after treatment, medications used for the treatment of neutropenia, and duration of neutropenia were collected. Time to absolute neutrophil count (ANC) recovery was the primary efficacy measure.

Results: Ambulatory and hospitalized patients comprised 11.3% and 45.1% of the enrolled patients, respectively, and a previous diagnosis of neutropenia was reported in 49.3% of the patients, as well. Neutropenia occurred in 13.7% (n=41), 45.5% (n=136), 27.4% (n=82), 11.4% (n=34), and 2.0% (n=6) of the patients during the first, second, third, fourth, and fifth cycles of chemotherapy, respectively. While the mean neutrophil count was 0.53±0.48 before treatment, a significant increase to 2.44±0.66 was observed after treatment (=0.0001). While 90.3% of patients had a neutrophil count <1.49 before treatment, all patients had a neutrophil count ≥1.50 after treatment. Neutropenia resolved within ≤4 days of filgrastim therapy in 60.1%, 56.7%, and 52.6% of the patients receiving biosimilar filgrastim 30 MIU, original filgrastim 30 MIU, and original filgrastim 48 MIU, respectively. However, there was no significant difference between the three arms (=0.468). Similarly, time to ANC recovery was comparable between the treatment arms (=0.332).

Conclusion: The results indicate that original filgrastim and biosimilar filgrastim have comparable efficacy in treating neutropenia. Biosimilar filgrastim provides a valuable alternative; however, there is need for further studies comparing the two products in different patient subpopulations.
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http://dx.doi.org/10.2147/OTT.S106342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783019PMC
January 2018

Bevacuzimab May Be Less Effective in Obese Metastatic Colorectal Cancer Patients.

J Gastrointest Cancer 2019 Jun;50(2):214-220

Department of Medical Oncology, Anadolu Medical Center, Istanbul, Turkey.

Purpose: The purpose of this study was to investigate whether obesity affects survival in metastatic colorectal cancer (mCRC) patients treated with bevacizumab combined with chemotherapy.

Methods: A total of 563 patients with mCRC who had received first-line chemotherapy in combination with bevacizumab were studied. Patients were grouped as obese (BMI levels > 30) or non-obese (BMI levels < 30). Progression-free survival (PFS) and overall survival (OS) were analyzed. Primary tumor location was also investigated in terms of PFS and OS.

Results: The median age of the patients was 59 years. The non-obese group had longer PFS than the obese group (P = 0.030). The 2-year survival rate of the non-obese group was also significantly higher (P = 0.036). The median PFS of non-obese patients was significantly longer in Kras wild-type patients (10.1 vs. 8.1 months, P = 0.010). Among patients with left-sided primary tumor location, median PFS and OS were significantly higher in the non-obese group (PFS non-obese, 11.5 months; obese, 8.8 months; P = 0.002) (OS non-obese, 29.4 months; obese, 21.4 months; P = 0.026).

Conclusions: Efficacy of bevacizumab may be lower in obese patients. Among patients with Kras wild-type left-sided tumors treated with bevacizumab-based regimens, the prognosis could be worse for obese patients than that for non-obese patients. There is a need for prospectively designed studies of obese patients to prove the efficacy and dosages of bevacizumab in treatment of mCRC.
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http://dx.doi.org/10.1007/s12029-017-0047-2DOI Listing
June 2019

Changes in 18F-FDG-PET/CT tumor metabolism are not consistent with pathologic complete response in hormone-positive breast cancer.

J BUON 2017 Sep-Oct;22(5):1191-1198

Department of Medical Oncology, Marmara University School of Medicine, Istanbul.

Purpose: Current evaluation of response to neoadjuvant chemotherapy (NAC) shows that it could achieve pathological complete response (pCR). The purpose of this study was to assess the consistency of maximum uptake values (SUVmax) changes and pCR in hormone-positive locally advanced breast cancer (LABC).

Methods: Ninety hormone-positive LABC patients treated at Marmara University Medical Oncology Clinic, Istanbul, Turkey, between 2009 and 2015 were retrospectively studied. All eligible patients (n=5) received NAC (4-8 cycles) and were evaluated for pCR. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG- PET/CT) scan was performed before and after the completion of NAC. The relative changes of SUVmax both in the primary tumor and the axilla were assessed for consistency with pCR.

Results: The patient median age was 46 years (range 26- 76). The patients 13.7% achieved pCR. Values of >50% (n=40) and <50% (n=11) SUVmax changes were not associated with pCR (15% and 18% respectively) (p=1.00). Patients with >75% SUVmax changes could achieve pCR of 20%. Interestingly, most patients with complete metabolic response did not achieve pCR (81%). The difference of the Ki67 levels before and after NAC, tumor localization, HER- 2 positivity, menopausal status, grade of differentiation, lymphovascular and perineural invasion were not associated with pCR.

Conclusion: SUVmax changes in later cycles of NAC as commonly practised in oncology clinics were not consistent with pCR (p=1.0). Complete metabolic response may not be associated with pCR in hormone-positive LABC. However, almost 80% of patients had >50% decrease in SUVmax and may still have a chance for conservative surgery and less postoperative morbidity. Therefore, 18F-FDG-PET/CT may still have a role to evaluate the tumor response with a need of larger studies and analysis for cost-effectiveness.
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August 2019