Dogan Koca

Clinical and Electrocardiography Changes in Patients Treated with Capecitabine

Background: We aimed to identify the incidence of cardiac events with capecitabine treatment. Methods: The study included 52 patients (median age 59 years) with cancer treated at our Medical Oncology Clinic between 2009 and 2010. Cardiac events from capecitabine treatment were classified into 4 groups: cardiac symptoms, physical signs, electrocardiography (ECG) findings, and severe adverse cardiac effects. Results: The patients received either single-agent capecitabine or a combination chemotherapy including capecitabine. After initiation of capecitabine, 18 patients (34.6%) had new onset cardiovascular symptoms, 6 (11.5%) had new onset physical signs and 17 (32.6%) had new onset ECG findings. New onset ECG findings included prolonged corrected QT interval (n = 10, 19.2%) and prolonged PR interval (n = 3, 5.8%). Severe adverse capecitabine-induced cardiac side effects were observed in 5.8% of the patients, but none of the patients had myocardial infarction or died. Conclusion: Cardiac events are not rare during capecitebine treatment and patients should be followed closely to avoid cardiac morbidity and mortality.

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

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

Biological Subtypes and Survival Outcomes in Breast Cancer Patients with Brain Metastases (Study of the Anatolian Society of Medical Oncology)

Background: The aim of this study is to determine the relationship between the survival outcomes and biological subtype in breast cancer patients with brain metastases. Methods: We retrospectively evaluated clinical data from 422 breast cancer patients with brain metastases between 2001 and 2011 from referral centers in Turkey. The study population was divided into four biological subtypes according to their hormone receptor status and HER2 expression. Results: Systemic treatment prolonged median overall survival (OS) after brain metastases in the entire group (14 vs. 3.2 months, p < 0.001). It also prolonged median OS after brain metastases in the triple negative (7.5 vs. 1.6 months, p = 0.010) and luminal A (14.3 vs. 7.1 months, p = 0.003) subgroups. The median OS for untreated patients, chemotherapy and/or hormonal therapy receiving patients, and chemotherapy and/or hormonal therapy plus targeted therapy receivers was 2, 5.8, and 17.7 months, respectively (p < 0.001), in the HER2-overexpressing subgroup. In the luminal B subgroup, it was 3.7, 5.3, and 15.4 months, respectively (p = 0.003). Conclusions: The use of systemic therapy improves OS after brain metastases in all biological subgroups. Targeted therapies also improve OS after brain metastases in HER2-positive patients. The combined use of targeted therapies and lapatinib are superior to single use and trastuzumab, respectively, in these patients.

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

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

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.

Relationship between Epidermal Growth Factor Receptor Gene Mutations and Clinicopathological Features in Patients with Non-Small Cell Lung Cancer in Western Turkey

BACKGROUND To investigate epidermal growth factor receptor (EGFR) gene mutations in patients with non- small cell lung cancer (NSCLC) and to analyze any relationship with clinicopathological features and prognosis. MATERIALS AND METHODS EGFR gene exons 18-21 in 48 specimens of paraffin-embedded tumor tissue from NSCLC patients were amplified by PCR, followed by direct sequencing and analysis of links to clinicopathological features and prognosis. RESULTS EGFR mutations were detected in 18 of 48 (42.6%) patients with NSCLC. There were 9 cases of mutations in exon 20, 7 in exon 19 and 2 in exon 21. Mutations were more frequently observed in women (5/7 pts, 71.4%) than in men (13/41 pts, 31.7%) (p=0.086) and in non-smokers (5/5 pts, 100%) than smokers (13/43 pts, 30.2%). There was negative correlation of EGFR mutations with smoking status (p=0.005). EGFR mutations were more frequently observed with adenocarcinoma histology (13/32 pts, 40.6%) than in other types (5/16 pts, 31.3%) (p=0.527). The patients with EGFR mutations had better survival than those with wild- type EGFR (p=0.08). There was no association of EGFR mutations with metastatic spread. CONCLUSIONS EGFR mutations in NSCLC were here demonstrated more frequently in females, non-smokers and adenocarcinoma histology in the western region of Turkey. Patients with EGFR mutations have a better prognosis.

Lapatinib plus Capecitabine for Brain Metastases in Patients with Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: A Review of the Anatolian Society of Medical Oncology (ASMO) Experience

Background: We investigated the clinical outcome of patients with brain metastases (BMs) from human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) treated with lapatinib and capecitabine (LC). Patients and Methods: A total of 203 patients with HER2+ MBC, who had progressed after trastuzumab-containing chemotherapy, were retrospectively evaluated in 11 centers between September 2009 and May 2011. 85 patients who had developed BMs before the initiation of treatment with LC were included. All patients had received prior cranial radiotherapy. 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). Results: The median follow-up was 10.5 months (range 1–38 months). An overall response rate of 27.1% was achieved, including complete response in 2 (2.4%) and partial response in 21 (24.7%) patients. Median progression-free survival was 7 months (95% confidence interval (CI) 5–9), with a median overall survival of 13 months (95% Cl 9–17). The most common side effects were hand-foot syndrome (58.8%), nausea (55.3%), fatigue (48.9%), anorexia (45.9%), rash (36.5%), and diarrhea (35.4%). Grade 3–4 toxicities were hand-foot syndrome (9.4%), diarrhea (8.3%), fatigue (5.9%), and rash (4.7%). There were no symptomatic cardiac events. Conclusion: LC combination therapy was effective and well-tolerated in patients with HER2+ MBC with BMs, who had progressive disease after trastuzumab-containing therapy.

Clinicopathological Features in Bilateral Breast Cancer

INTRODUCTION AND PURPOSE The frequency of bilateral breast cancer is 1.4-11.0% among all breast cancers. It can present as synchronous (SC) or metachronous (MC). Data regarding clinical course of bilateral breast cancer are scarce. In this study, we therefore evaluated demographic, pathological and clinical characteristics, treatments and responses in bilateral breast cancer cases; making distinctions between metachronous-synchronous and comparing with historic one-sided data for the same parameters. MATERIALS AND METHODS One hundred fifty bilateral breast cancer cases from ten different centers between 2000 and 2011 were retrospectively scanned. Age of the cases, family history, menopausal status, pathological features, pathological stages, neoadjuvant, surgery, adjuvant and palliative chemotherapy/radiotherapy were examined in the context of the first and second occurrence and discussed with reference to the literature. RESULTS Metachronous and synchronous groups showed similar age, menopausal status, tumor type, HER2/neu expression; the family history tumor grade, tumor stage, ER-negativity rate, local and distant metastases rates, surgery, adjuvant chemotherapy application rates were identified as significantly different. Palliative chemotherapy response rate was greater in the metachronous group but median PFS rates did not differ between the groups. CONCLUSION Although bilateral breast cancer is not frequent, MC breast cancer is different from SC breast cancer by having more advanced grade, stage, less ER expression, more frequent rates of local relapse and distant metastasis and better response to chemotherapy in case of relapse/metastasis.

Lapatinib plus capecitabine for HER2-positive advanced breast cancer: a multicentre study of Anatolian Society of Medical Oncology (ASMO)

Abstract Lapatinib is the first dual tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 (HER2/neu) and epidermal growth factor receptor (EGFR). The present study evaluated the efficacy and tolerability of the combination of lapatinib and capecitabine in patients with metastatic breast cancer (MBC) who progressed after therapy with trastuzumab, a taxane and/or anthracycline. A total of 203 patients with a median age of 48 years (range: 25–82 years) were evaluated retrospectively in 11 centres between September 2007 and May 2011. All the patients had HER2-positive MBC progressing after trastuzumab and chemotherapy including an anthracycline and/or taxane. All patients were treated with the combination of lapatinib (1250 mg/day, continuously) and capecitabine (2000 mg/m2 on days 1 through 14 of a 21-day cycle). Data on demographics, clinical outcome, and toxicity were collected for descriptive analyses. The median follow-up was 10·7 months (range: 1–40 months). An overall response rate (ORR) of 33·4% was achieved including 7 complete responses (CR, 3·4%), 61 partial responses (PR, 30·0%), and 44 stable disease (37·9%). Clinical benefit rate of 71·3% was achieved. Median progression-free survival (PFS) was 7 months (95% CI: 6–10 months), with a median overall survival (OS) of 15 months (95% CI: 12–18 months). The most common side effects were hand–foot syndrome (46·8%), nausea (42·3%), fatigue (42·2%), anorexia (38·5%), diarrhea (31·5%), and rash (29·6%). Grade 3–4 toxicities were identified as hand foot syndrome (7·9%), diarrhea (6·9%), fatigue (5·9%), and rash (5·4%). There were no symptomatic cardiac events. Lapatinib and capecitabine combination therapy is effective and well tolerated in patients with MBC who had progressive disease after trastuzumab, taxane, and/or anthracycline therapy, as evidenced by this retrospective evaluation. Toxicity was mild to moderate with low grade 3–4 toxicity.

Long-term outcomes and prognostic factors of high-risk malignant melanoma patients after surgery and adjuvant high-dose interferon treatment: a single-center experience.

Background: Surgical excision constitutes an important part of the treatment of local advanced malignant melanoma. Due to the high recurrence risk, adjuvant high-dose interferon therapy is still the only therapy used in stage IIB and III high-risk melanoma patients. Methods: One hundred two high-risk malignant melanoma patients who received high-dose interferon-α-2b therapy were evaluated retrospectively. The clinicopathological features, survival times, and prognostic factors of the patients were determined. Results: The median disease-free and overall survival times were 25.2 and 60.8 months, respectively. Our findings revealed that male gender, advanced disease stage, lymph node involvement, lymphatic invasion, the presence of ulceration, and a high Clark level were significant negative prognostic factors. Conclusion: In light of the favorable survival results obtained in this study, high-dose interferon treatment as adjuvant therapy for high-risk melanoma is still an efficient treatment and its possible side effects can be prevented by taking the necessary precautions.