Suleyman Buyukberber

Bevacizumab + Capecitabine as Maintenance Therapy after Initial Bevacizumab + XELOX Treatment in Previously Untreated Patients with Metastatic Colorectal Cancer: Phase III ‘Stop and Go' Study Results - A Turkish Oncology Group Trial

Objective: It was the aim of this study to evaluate maintenance therapy with bevacizumab + capecitabine following induction with bevacizumab + capecitabine + oxaliplatin (XELOX) versus bevacizumab + XELOX until progression as first-line therapy in metastatic colorectal cancer (mCRC). Methods: Patients received either bevacizumab (7.5 mg/kg) + XELOX (capecitabine 1,000 mg/m2 twice daily on days 1-14 + oxaliplatin 130 mg/m2 on day 1 every 3 weeks) until disease progression (arm A) or the same doses of bevacizumab + XELOX for 6 cycles followed by bevacizumab + capecitabine until disease progression (arm B). The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. Results: One hundred and twenty-three patients were randomized. Treatment compliance was similar in both groups. Median PFS was significantly longer for arm B than for arm A (11.0 vs. 8.3 months; p = 0.002). There was no significant difference between the two arms for ORR (66.7 vs. 59.0%; p = 0.861) or median OS (23.8 vs. 20.2 months; p = 0.100). Tolerability was acceptable in both treatment arms; the most frequent grade 3/4 treatment-related adverse events (arm B vs. arm A) were fatigue (6.6 vs. 16.1%), diarrhoea (3.3 vs. 11.3%), anorexia (3.3 vs. 11.3%), and neuropathy (1.6 vs. 8.1%). Conclusions: Maintenance therapy with bevacizumab + capecitabine can be considered an appropriate option following induction bevacizumab + XELOX in patients with mCRC instead of continuation of bevacizumab + XELOX.

The relationships between plasma and erythrocyte antioxidant enzymes and lipid peroxidation in patients with rheumatoid arthritis

Objective. The present study was undertaken to evaluate the activities of some key erythrocyte and plasma enzymes participating in free radical metabolism and the end product of lipid peroxidation in rheumatoid arthritis, and whether there are any differences for these parameters between newly diagnosed untreated patients and rheumatoid arthritis patients on drug therapy. Patients and methods. Superoxide dismutase and catalase activities, and malondialdehyde levels were determined in erythrocytes and plasma samples from 54 patients with rheumatoid arthritis (21 of whom without any treatment and 33 on classical therapy regimens) and from 33 healthy controls. Results. There were no statistically significant differences in mean values of activities of the erythrocyte enzymes between the patients and controls. Malondialdehyde levels were significantly increased in both newly diagnosed untreated patients and patients on drug therapy compared to control subjects. Malondialdehyde levels were lower in the treated group than the newly diagnosed untreated group (0.214 ± 0.111 μmol/L and 0.388 ± 0.075 μmol/L, respectively) (P < 0.0001). Mean plasma superoxide dismutase activity was lower in the group of newly diagnosed untreated patients compared to those of the treated and control groups (1.31 ± 0.69 U/mL, 1.79 ± 0.94 U/mL and 2.48 ± 0.95 U/mL, respectively) (P < 0.0001, untreated vs control groups). Conclusions. These results suggest sufficient antioxidant enzyme activities in erythrocytes in patients with rheumatoid arthritis and also increased lipid peroxidation end products in newly diagnosed untreated patients compared to control group and patients on drug therapy.

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.

Lapatinib plus Capecitabine for HER2-Positive Advanced-Stage Breast Cancer in Elderly Women: Review of the Anatolian Society of Medical Oncology (ASMO) Experience.

Background: The efficacy and safety of the lapatinib and capecitabine combination remain elusive in elderly patients with metastatic breast cancer (MBC), who progress after trastuzumab-based therapy. Patients and Methods: A total of 26 patients with HER2-positive MBC were included in this retrospective multicenter study. Median age was 69 years (range 65-82 years). All patients were treated with the combination of lapatinib (1,250 mg/day, continuously) and capecitabine (2,000 mg/m2 on days 1-14 of a 21-day cycle). Data on demographics, clinical outcome, and toxicity were collected for descriptive analyses. Results: The median follow-up was 10 months (range 2-31 months). An overall response rate of 33.4% was achieved, including 1 complete response (3.8%), and 8 partial responses (30.8%). Median progression-free survival was 7 months (95% confidence interval (CI) 5-8), and the median overall survival was 15 months (95% CI 11-19). Most common side effects were fatigue (53.8%), diarrhea (46%), vomiting (36.3%), hand-foot syndrome (34.5%), and anorexia (34.6%). Grade 3-4 toxicities were identified as hand-foot syndrome (3.8%), diarrhea (7.6%), and fatigue (11.5%). There were no symptomatic cardiac events. Conclusion: Lapatinib and capecitabine combination therapy was effective and well tolerated in elderly patients with MBC, who had progressive disease after trastuzumab-based therapy.

Efficacy and Safety of Concomitant Chemoradiotherapy with Cisplatin and Docetaxel in Patients with Locally Advanced Squamous Cell Head and Neck Cancers

BACKGROUND Chemoradiation (CRT) using cisplatin-based regimens has become the standard of care in the treatment of squamous cell head and neck cancers (SCHNC). The impact of taxanes as radiosensitizing agents with concurrent CRT regimens is unknown. We therefore retrospectively evaluated the efficacy and tolerability of a weekly cisplatin+docetaxel combination with CRT in locally advanced SCHNC. METHODS Sixty-six patients with locally advanced SCHNC (39.4% stage IV, 53% stage III, and 7.6% stage II) were assessed retrospectively. Total radiation dose to the PTV of gross disease (primary and/or node) was 70 Gy/ 35 fractions, 5 fractions per week. Minimum doses of 60 Gy and 50 Gy were administered to PTVs of elective high risk and low risk disease, respectively. Chemotherapy (CT) consisted of weekly cisplatin (20 mg/m2) +docetaxel (20 mg/m2) concurrently with RT. RESULTS The median age of the patients was 58 years (range, 32-77). Objective response rate was 83.3%. The 2-year progression-free survival (PFS) and overall survival (OS) were 75.7% and 78.3%, respectively. The most common grade 3 and 4 toxicities were mucositis (36.4%), nausea and vomiting (12.1%), neutropenia (4.5%). CONCLUSION Weekly cisplatin and docetaxel concurrent with RT for locally advanced SCHNC was found tolerable with high efficacy.

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

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

Low-dose docetaxel/cisplatin - leucovorin and 46 hour infusional fluorouracil in metastatic gastric carcinoma.

BACKGROUND Phase II and III trials of docetaxel, cisplatin and fluorouracil (DCF) have shown superior efficacy versus cisplatin and fluorouracil alone but with high rates of hematologic toxicity in metastatic gastric cancer cases. To reduce toxicity while maintaining the efficacy of DCF, we investigated low dose docetaxel (D), cispatin (C) - leucovorin and fluorouracil (De Gramont regimen). PATIENT AND METHODS Chemotherapy-naive patients with metastatic gastric cancer (MGC) received D 60 mg/m2 on day 1 and cisplatin 30 mg/m2 on day 1-2 and the De Gramont regimen (Folinic acid 400 mg/m2 on day 1 and 5-FU 2400 mg/m2/46 h continuous infusion) every 3 weeks. The primary endpoint was response rate. RESULTS One hundred twenty patients with a median age of 52.5 years (range, 32-78) received a median of 6 cycles (range, 2-12 cycles). Of the 120 evaluable patients, 4 showed complete remission and 36 achieved a partial response. The overall response rate was 56.6%. Twenty eight patients (23.3%) showed stable disease and 52 (43.3%) progression. The median time to progression was 7 months (95%CI 6-7.9). The median overall survival was 15 months (95%CI 13.7-16.2). The most frequent hematological toxicity was leucopenia, which occurred at grade 3/4 intensity in 24 patients (20%). CONCLUSIONS Low-dose DC- De Gramont regimen is active in MGC with a tolerable toxicity profile.

Treatment and Prognostic Factors in Primary Peritoneal Carcinoma: A Multicenter Study of the Anatolian Society of Medical Oncology (ASMO)

Background: In this study, we aimed to evaluate the clinicopathological characteristics and prognosis of patients with primary peritoneal carcinoma (PPC), and the effectiveness and toxicity of first-line platinum/taxane combination therapy. Patients and Methods: We retrospectively evaluated 79 patients with PPC, who were treated and followed up between December 2001 and August 2012 at 10 medical oncology clinics. Results: All patients were female, with a median age of 63 years (range 34-79 years). Histopathological diagnoses included primary peritoneal serous carcinoma (PPSC) (n = 69) and mixed epithelial carcinoma of the peritoneum (MEC) (n = 10). Patients received first-line treatment with carboplatin/paclitaxel (n = 67) or cisplatin/paclitaxel (n = 12) combination therapy. Overall response rate, median progression-free survival, and median survival time in the paclitaxel/carboplatin group and the paclitaxel/cisplatin group were 74.6 vs. 75%, 15.6 vs. 37.8 months, and 41 vs. 70.3 months, respectively. In multivariate analysis, favorable prognostic factors were: ECOG performance status 0 (p < 0.001) and optimal cytoreduction (p = 0.03). Conclusion: PPC is a rare, heterogeneous disease. ECOG performance status and optimal cytoreduction are important prognostic factors regarding survival rates. Platinum/taxane combination therapy is an effective and tolerable regimen in this patient group.

Efficacy and safety of raltitrexed combinations with uracil- tegafur or mitomycin C as salvage treatment in advanced colorectal cancer patients: a multicenter study of Anatolian Society of Medical Oncology (ASMO).

BACKGROUND There is no standard treatment for patients with colorectal cancer (CRC) progressing after irinotecan and oxaliplatin treatment. Here we aimed to retrospectively evaluate the efficacy and tolerability of raltitrexed in combination with oral 5-fluoropyrimidine (uracil tegafur-UFT) or mitomycin C as salvage therapy in mCRC patients. MATERIALS AND METHODS A total of 62 patients who had received raltitrexed combined with UFT or mitomycin C were identified between December 2008 and June 2013. They were given raltitrexed 2.6 mg/m2 (max 5 mg) i.v. on day 1 in combination with either oral UFT 500 mg/day on days 1-14 every 3 weeks (group A) or mitomycin C 6 mg/m2 i.v. on day every 3 weeks (group B). RESULTS Forty-two patients (67.7%) were in group A and 20 (32.2%) in group B. In 15 patients (24%) grade 3/4 toxicity was observed, resulting in dose reduction, and in 13 patients (20.9%) dose delay was necessary. The median progression free survival (PFS) was 3 months (95%CI 2.65-3.34) and median overall survival (OS) was 6 months (95%CI 2.09-9.90) in the whole group. Median PFS was 3 months (95%CI 2.60-3.39) in group A vs 3 months (95%CI 1.64-4.35) in group B (p=0.90). Median OS was 6 months (95%CI 2.47-9.53) in group A vs 12 months (95%CI 2.83-21.1) in group B (p=0.46). CONCLUSIONS The combination of raltitrexed with UFT or mitomycin C seem to be a salvage therapy option due to safety profile and moderate clinical activity in heavily-pretreated mCRC patients.

Docetaxel and cisplatin in first line treatment of patients with unknown primary cancer: a multicenter study of the Anatolian Society of Medical Oncology.

BACKGROUND The overall prognosis for cancers of unknown primary (CUP) is poor, median overall survival (OS) being 6-12 months. We evaluated our multicentric retrospective experience for CUP administered docetaxel and cisplatin combination therapy. MATERIALS AND METHODS A total of 29 patients that were pathologically confirmed subtypes of CUP were included in the study. The combination of docetaxel (75 mg/m2, day 1) and cisplatin (75 mg/m2, day 1) was performed as a first line regimen every 21 days. RESULTS The median age was 51 (range: 27-68). Some 17 patients had multimetastatic disease on the inital diagnosis. Histopathological diagnoses were well-moderate differentiated adenocarcinoma (51.7%), undifferentiated carcinoma (27.6%), squamous cell cancer (13.8%), mucoepidermoid carcinoma (3.4%) and neuroendocrine differentiated carcinoma (3.4%). Median number of cycles was 3 (range: 1-6). Objective response rate was 37.9% and clinical benefit was 58.6%. Median progression free survival (PFS) and overall survival (OS) were 6 months (range: 4.3-7.7 months) and 16 months (range: 8.1-30.9 months), respectively. Fourteen patients (60.8%) were treated in a second line setting. There was no treatment related death. Most common toxicities were nausia-vomiting (44.6%) and fatigue (34.7%), serious cases (grade 3/4) suffering nausia-vomiting (10.3%), neutropenia (13.8%) and febrile neutropenia (n=1). CONCLUSION The combination of cisplatin and docetaxel is an effective regimen for selected patients with CUP.