Beyond traditional therapies: clinical significance of complex molecular profiling in patients with advanced solid tumours-results from a Turkish multi-centre study.

OBJECTIVE: The objective of this multi-centre, real-world study was to examine the potential influence of comprehensive molecular profiling on the development of treatment decisions or adjustments for patients with advanced solid malignancies. We then evaluated the impact of these informed choices on patient treatment outcomes. METHODS: The study encompassed 234 adult patients (mean age: 52.7 ± 14.3 years, 54.7% women) who were diagnosed with solid tumours at 21 different medical centres in Turkey. Remarkably, 67.9% of the patients exhibited metastasis at the time of diagnosis. We utilized an OncoDNA (Gosselies, Belgium) platform (OncoDEEP) integrating next-generation sequencing with additional tests to harvest complex molecular profiling data. The results were analyzed in relation with two specific outcomes: (i) the impact on therapeutic decisions, including formulation or modifications, and (ii) associated treatment response. RESULTS: Out of the 228 patients with final molecular profiling results, 118 (50.4%) had their treatment modified, whilst the remaining 110 (47.0%) did not. The response rates were comparable, with 3.9 versus 3.4% for complete response, 13.6 versus 29.3% for partial response, 66.9 versus 51.7% for progressive disease and 15.5 versus 15.5% for stable disease for treatments informed and not informed by complex molecular profiling, respectively (P = 0.16). CONCLUSION: Our real-world findings highlight the significant impact of complex molecular profiling on the treatment decisions made by oncologists for a substantial portion of patients with advanced solid tumours. Regrettably, no significant advantage was detected in terms of treatment response or disease control rates.

Value of caffeic acid phenethyl ester pretreatment in experimental sepsis model in rats.

BACKGROUND AND AIM: The aim of this study was to determine the actions of caffeic acid phenethyl ester (CAPE) on the changes of endothelin-1 (ET-1) level, tumor necrosis factor- (TNF-) alpha, and oxidative stress parameters such as superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels in experimental sepsis model in rats. MATERIALS AND METHODS: Twenty-four rats were randomly divided into three experimental groups: sham (group 1), sepsis (group 2), and sepsis + CAPE (group 3), n = 8 each. CAPE was administered (10 µmol/kg) intraperitoneally to group 3 before sepsis induction. Serum ET-1, serum TNF-alpha, tissue SOD activity, and tissue MDA levels were measured in all groups. RESULTS: Pretreatment with CAPE decreased ET-1, TNF-alpha, and MDA levels in sepsis induced rats. Additionally SOD activities were higher in rats pretreated with CAPE after sepsis induction. CONCLUSION: Our results demonstrate that CAPE may have a beneficial effect on ET and TNF-alpha levels and oxidative stress parameters induced by sepsis in experimental rat models. Therefore treatment with CAPE can be used to avoid devastating effects of sepsis.

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.

Paclitaxel plus doxorubicin chemotherapy as second-line therapy in patients with advanced urothelial carcinoma pretreated with platinum plus gemcitabine chemotherapy.

BACKGROUND: We retrospectively evaluated the efficacy and toxicity of paclitaxel plus doxorubicin as a second-line treatment in patients with urothelial carcinoma, who had not responded to a prior platinum plus gemcitabine combination. PATIENTS AND METHODS: All patients received intravenous infusions of paclitaxel (175 mg/m(2)/h) and doxorubicin (50 mg/m(2)/30 min) on day 1. Chemotherapy courses were repeated every 21 days. RESULTS: The median followup duration was 13.5 months (range 2.8-22.4 months). Complete and partial responses were observed in 2 (5.6%) and 10 (27.8%) patients, respectively. Median overall survival was 8.9 months (95% confidence interval (CI): 6.2-11.6). Median time to progression was 3.8 months (95% CI: 2.7-4.8). The most common hematologic toxicities were neutropenia (n = 21, 58.3%), thrombocytopenia (n = 10, 27.8%), and anemia (n = 9, 25%). The most common nonhematologic toxicities consisted of fatigue (n = 15, 41.7%), nausea/vomiting (n = 13, 36.1%), peripheral neuropathy (n = 11, 30.6%), and mucositis (n = 6, 16.7%). Dose reductions by 25-35% were performed in 6 (16.7%) patients because of grade 3/4 toxicity. Anthracycline-related heart failure did not occur. CONCLUSION: 3-weekly courses of cyclic paclitaxel plus doxorubicin were found to be effective and tolerable in patients with urothelial carcinoma, who had not responded to prior platinum- and gemcitabine-based chemotherapy.

Docetaxel combined with oral etoposide as second-line treatment for advanced gastric carcinoma after failure of platinum- and fluoropyrimidine-based regimens.

BACKGROUND: Platinum, antracyline, and fluoropyrimidine combination chemotherapy has been widely used as a first-line treatment for advanced gastric cancer (AGC). In the present study, we determined the efficacy and the safety of docetaxel and oral etoposide as second-line combination chemotherapy after failure of commonly used combination regimens in AGC. METHODS: Patients with histologically proven gastric cancer and measurable metastatic disease received docetaxel 75 mg/m(2) as a 1-h intravenous infusion on day 1, and oral etoposide 50 mg/m(2) once daily on days 1-5, every 3 weeks until disease progression or unacceptable toxicities. RESULTS: Between June 2006 and September 2008, 32 patients, of median age 60 years (range 32-77 years) were included in the study. Overall response rate was 9.4% and 31.3% of patients achieved a stable disease. Median progression-free survival was 3 months (95% CI, 2.5-3.5). Median overall survival was 6 months (95% CI, 3.8-8.2) with 16.9% 1-year survival rate. Grade 3-4 toxicities included neutropenia (28.8%), febrile neutropenia (18.8%), thrombocytopenia (3.1%), nausea and vomiting (15.6%), diarrhea (9.4%), and mucositis (6.2%). CONCLUSION: Docetaxel and oral etoposide combination was moderately effective and safe in appropriately selected AGC patients after failure of platinum- and fluoropyrimidine-based combination regimens.

UFT plus oral folinic acid with alternating oral and intravenous vinorelbine in patients with metastatic breast cancer previously treated with anthracyclines and taxanes.

BACKGROUND: We retrospectively evaluated the activity and toxicity of uracil/tegafur (UFT) plus oral folinic acid in combination with vinorelbine (alternating intravenous (IV) on day 1 and oral on day 8) in patients with metastatic breast cancer. PATIENTS AND METHODS: Treatment consisted of IV vinorelbine 25 mg/m(2) on day 1 and 60 mg/m(2) orally on day 8, and oral UFT 300 mg/m(2) plus leucovorin 60 mg/m(2) on days 1-14 with 21 days interval. All patients were refractory to anthracyclines and taxanes. RESULTS: Partial response (PR) was observed in 3 (9.7%) and stable disease (SD) was observed in 13 (41.9%) patients. Total clinical benefit (PR + SD) of the combination was 51.6%. The median response duration was 3 (range 1-11.8) months. Median overall survival was 9.8 months (95% confidence interval (CI): 7.5-12.1), and median time to progression was 3.4 months (95% CI: 2.3-4.5). The most common toxicities were hematologic, including 4 (12.9%) cases of grade 3 neutropenia and 4 (12.9%) cases of grade 4 neutropenia. Grade 3 diarrhea was reported in 2 (3.2%) patients. 3 (9.7%) patients had hand-foot syndrome. Febrile neutropenia was observed in 1 patient. CONCLUSIONS: Although the combination is safe and convenient in clinical practice, it has only moderate activity in metastatic breast cancer patients.

Multiple subcutaneous nodular metastases from transitional cell carcinoma of the bladder.

Skin metastasis from transitional cell carcinoma (TCC) of the bladder is rare. In this report an uncommon metastasis of TCC of the bladder is presented.

Prognostic factors and COX-2 expression in advanced stage esophageal squamous cell carcinoma.

Cyclooxygenase-2 (COX-2) is overexpressed in various types of human malignancies, including squamous cell carcinomas of the esophagus, but its clinicopathologic role in esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study was to analyze expression of COX-2 in ESCC and to correlate this expression with clinicopathologic parameters and survival. From 1999 to 2003, endoscopic tissue samples from 110 patients with ESCC were collected for analysis. COX-2 expression was examined through immunohistochemical staining. Clinicopathologic data were analyzed to verify significance. COX-2 expression was detected in 50 of 110 ESCC specimens (45%). COX-2 expression was negative to weak in 73% (COX-2 low) and moderate to strong in 27% (COX-2 high) of tumors. Statistical differences between COX-2 high and COX-2 low were found according to status of the stage (stage IVM1a/IVM1b) (P=.001): cancer antigen (CA) 19-9 (normal/high) (P%.011), CA 12-5 (normal/high) (P=.011), and CA 15-3 (normal/high) (P=.035). Survival was significantly reduced among patients with high COX-2 expression (median overall survival, 3 mo) when compared with the COX-2 low group (median overall survival, 6 mo) (P=.0001). In the univariate analysis, age, body mass index, stage, COX-2, lactate dehydrogenase, CA 12-5, and CA 15-3 were significant factors for survival. With the use of COX regression analysis, only stage (P=.000), COX-2 (P=.000), lactate dehydrogenase (P=.023), and CA 15-3 (P=.002) were independent prognostic factors. Results showed that in patients with ESCC, COX-2 overexpression was significantly correlated with visceral metastases IVM1b). COX-2 overexpression is an unfavorable prognostic factor in ESCC.

Prognostic factors in patients with aggressive non-Hodgkin's lymphoma without complete response to first-line therapy.

This study was conducted to retrospectively identify the prognostic factors that specifically predict survival rates of patients with aggressive non-Hodgkin's lymphoma who did not achieve a complete response (CR) to first-line therapy. Prognostic factors in terms of survival were analyzed in 76 adult patients with non-Hodgkin's lymphoma who had failed to achieve CR to first-line chemotherapy (CT) regimens administered at Istanbul University, Institute of Oncology, between February 1989 and October 1998. A total of 41 patients were female, and median age was 60 y (range, 18-87 y). Twenty-seven patients (35%) had primary refractory disease (stable disease + progressive disease). A partial response (PR) was demonstrated in 49 (65%). In all, 92% had been administered anthracycline on the basis of computed tomography findings. Of 27 patients with primary refractory disease, 20 died because of initial CT toxicity or disease progression. A total of 10 patients with primary refractory disease underwent second-line CT. CR was observed in only 1 of those patients. Of the 49 patients who had a PR to first-line therapy, 31 died because of disease progression. Of those patients, 14 underwent second-line CT. Four patients were observed to have a CR. Median overall survival (OS) in all patients was established at 15 mo (range, 11-19 mo), and 5-y OS was 25%. On the other hand, median OS in patients with primary refractory disease was 7.6 mo (range, 5.7-9.4 mo) and was observed to be 17.8 mo (range, 9.4-26.1 mo) in patients with a PR. The difference in survival rates between patients with primary refractory disease and those with a PR was significant (P=.005). Although median OS was 18.1 mo (range, 8.4-27.8 mo) in patients with intermediate-grade histology, it was 6.1 mo (range, 1-11.7 mo) in patients with highgrade histology (P=.001). As a result of univariate analysis, significant rognostic factors associated with OS included histologic grade (intermediate/high) (P=.001), response to initial therapy (primary refractory disease/PR) (P=.005), performance status (0-2/2-4) (P=.024), and International Prognostic Index risk groups (low/low intermediate/intermediatehigh high risk) (P=.004). Multivariate analysis revealed that independent prognostic parameters associated with OS included response to initial therapy (P=.009) and histologic grade (P=.001). Although prognosis is rather poor in patients with high histologic grade and primary refractory disease, patients with a PR have a slightly better prognosis.

Incidence of renal insufficiency in cancer patients.

The frequency of chronic renal insufficiency among cancer patients is unclear. The aim of this study was to determine the frequency of impaired renal function within a population of cancer patients. One thousand two hundred seventeen patients (563 women, 654 men) with cancer underwent serum creatinine concentration and glomerular filtration rate (GFR) evaluations. The Cockcroft-Gault formula was used to estimate the GFR from the creatinine clearance (Cl(cr)). Renal insufficiency was defined as a GFR 1.2 mg/dL). According to the Cockcroft-Gault formula evaluations, however, 330 (27.1%) of the patients had an estimated GFR <90 mL/min. Among these, the Clcr was between 60 and 89 mL/min in 241 patients (19.8%); 30 and 59 mL/min in 75 patients (6.2%); and 15 and 29 mL/min in 7 patients (0.6%); 7 patients (6%) had a Cl(cr) <15 mL/min. As a result, 21.2% of patients demonstrating a normal serum creatinine level had abnormal renal function. Renal function should be evaluated in all cancer patients, regardless of their serum creatinine level, before any drug regimen is administered. The Cockcroft-Gault formula appears to be more accurate than serum creatinine concentration for diagnosing renal insufficiency in patients with cancer, but more prospective studies in this population will be necessary to confirm this finding.

Fatal lactic acidosis due to leukemic transformation in a patient with non-Hodgkin's lymphoma: case report.

Lactic acidosis (LA) associated with hematologic malignancies is uncommon, life-threatening, and generally occurs in adults. Its pathogenesis is poorly understood. This is a case report of LA due to leukemic transformation that occurred in a patient with non-Hodgkin's lymphoma (NHL). A 24-year-old man with NHL was admitted to the hospital with dyspnea. Venous blood gas analysis revealed metabolic acidosis (pH 7.05; HCO3 6 mEq/L; BE 22 mmol/L; anion gap 28 mEq/L); the patient had an elevated plasma lactate concentration (12 mmol/L) and low glucose concentration (38 mg/dL). There was no reason other than leukemia-such as infection, circulatory failure, or drug use-for the development of severe LA. This case report shows that in patients with NHL, leukemic transformation may give rise to LA.

Predictive and prognostic values of BubR1 and synuclein-gamma expression in breast cancer.

The aim of this study is to determine the expression level of spindle assembly checkpoint (SAC) proteins-BubR1 and synuclein-gamma (SNCG) in human breast cancer tissues and to test whether there is a relationship between their expression levels and clinicopathologic parameters including respons to taxanes, tumor grade, estrogen receptor (ER) pozitivity, HER2 status, and overall survival (OS). We analyzed retrospectively paraffin-embedded tissue sections from 55 breast cancer patients whose clinical outcomes had been tracked after taxane treatment in neoadjuvan and metastatic setting. The expression status of BubR1 and SNCG was defined by immunohistochemistry (IHC) using the anti-BubR1 and anti-SNCG antibody. The BubR1 and SNCG was overexpressed in 38% and 62% of the study group, respectively. There was borderline significant correlation between low BubR1 expression and increased taxane sensitivity (P=0.05). In contrast, high SNCG expression was significantly associated with decreased taxane sensitivity (P=0.01). There was no association between the clinicopathologic parameters including histologic grade, ER positivity and HER2 status and the level of these proteins. However, triple negative tumors showed significantly more high BubR1 expression than those other molecular subtypes (P=0.04). Kaplan-Meier survival analysis failed to show a significant correlation between expression levels of BubR1 and SNCG and overall survival although patients with low levels of both proteins had a marginally longer survival time compared to those with high levels. In summary, our data suggest that both BubR1 and SNCG may be promising predictive marker rather than prognostic marker in patients with breast cancer.

Prognostic factors in localized aggressive non-Hodgkin's lymphoma.

To identify the prognostic factors that specifically predict survival rates of patients with localized aggressive non-Hodgkin's lymphoma (NHL), a retrospective study including 118 patients with clinical stage I and II NHL treated at the Institute of oncology, Istanbul University between 1989 and 1998 was conducted. Patients were treated either with radiotherapy alone, radiotherapy and adjuvant chemotherapy, or chemotherapy (with or without adjuvant radiotherapy). The 5-year disease-free survival (DFS) and overall survival rates were calculated, and univariate and multivariate analyses were performed to identify the significance of various prognostic factors such as gender, age, performance status, stage (I versus II), B symptoms, extranodal involvement, gastrointestinal tract disease, erythrocyte sedimentation rate, bulky disease, histologic grade, serum lactate dehydrogenase level, serum beta2-microglobulin level, serum albumin level, treatment regimen, remission status, and the International Prognostic Index risk groups, which may have an influence on the outcome of patients with NHL. The overall 5-year survival rate was 52% with a median follow-up of 30 months. The complete response rate was 68%, and the 5-year DFS of complete responders was 70%. Cox multivariate regression analysis showed that incomplete response, low serum albumin, bulky disease (>10 cm), and high grade histology were the pretreatment factors associated with shorter survival. When remission status was included in the model, the attainment of a complete response was the major determinant of long-term survival; however, low albumin level was still a significant adverse predictor for survival in multivariate analysis. These factors need to be evaluated for analyzing the outcome of treatment and to identify better therapeutic strategies.

Aggressive non-Hodgkin's lymphoma treated at the Institute of Oncology, Istanbul: treatment, outcome, and prognostic factors.

In an unselected group of patients with aggressive non-Hodgkin's lymphoma (A-NHL) treated at our institution during a 10-year period (1989-1998), we studied the treatment outcome and influence of possible prognostic factors. Two hundred one patients with A-NHL were analyzed retrospectively with regard to personal, treatment, and disease-specific characteristics. Median age was 55 years (range: 16-87 years) and the male:female ratio was 1.5. During a median follow-up of 26 months, the overall response rate was 74% (complete response 63%, partial response 11%). The 2- and 5-year disease-free survival rates were 49 +/- 3% (mean +/- SEM) and 41 +/- 4%, respectively. In a univariate analysis, the following variables were associated with prognosis in terms of survival: patient age, clinical stage, performance status, B symptoms, erythrocyte sedimentation rate, treatment response, and histologic grade of tumor. In multivariate analyses, patient age, performance status, and treatment response emerged as independent prognostic factors for survival.

Anemia in oncology practice: relation to diseases and their therapies.

Anemia is common in patients with cancer and is a frequent complication of myelosuppressive chemotherapy. In this study, we investigated the incidence and severity of chemotherapy-induced anemia caused by the most common chemotherapy regimens, including the new generation of chemotherapeutic agents, used in the treatment of the major nonmyeloid malignancies in adults. Five hundred fifty-two patients with histologically proven carcinoma originating from breast (n = 165), lung (n = 128), colon (n = 75), ovary (n = 84), and malignant lymphoma (n = 100) were included in this study. Hemoglobin levels for each patient were measured with an automatic counter during both pretreatment and before each chemotherapy cycle during therapy. To document the incidence of anemia, the National Cancer Institute grading system was used. Before chemotherapy, 44% of patients with breast carcinoma had anemia. There was a 16% increase in the incidence of anemia after chemotherapy. Severe anemia was observed in less than 1% of patients. No difference was found in the incidence of anemia between the fluorouracil, doxorubicin, cyclophosphamide (FAC) and cyclophosphamide, methotrexate, fluorouracil (CMF) regimens used in the adjuvant setting. However, single-agent chemotherapy with newer generation caused more anemia when compared with the FAC regimen (p < 0.005). Chemotherapy resulted in a significant decrease in hemoglobin levels when compared with pretreatment values in patients with lung cancer (p < 0.001). During treatment, the increase in the incidence of grade II anemia was associated with a parallel decrease in the incidence of grade I anemia. The incidence of severe anemia did not exceed 15%. The incidence of anemia was equivalent in both patients with small-cell lung cancer and those with non-small-cell lung cancer treated with the etoposide and cisplatin (EP) combination. Seventy-one percent of patients with colon cancer had anemia before initiation of chemotherapy. No difference was observed in posttreatment hemoglobin values compared with pretreatment values. Patients treated with irinotecan and fluorouracil and leucovorin (FUFA) combination showed similar rates of anemia. Incidence of anemia in patients with ovarian cancer at admission was 68%. Chemotherapy resulted in a prominent increase in incidence of anemia, which increased to 91.5%. There was an increase in grade II anemia, which corresponded to the decrease in grade I anemia. Less than 10% of patients developed severe anemia. No difference in the incidence of anemia was observed in patients with ovarian cancer treated with either cisplatin and cyclophosphamide or cisplatin combination. Showing a high incidence of anemia (82%) at presentation, hemoglobin levels in patients with malignant lymphoma were unaltered with chemotherapy. Severe anemia occurred in less than 3% of patients. There was a higher incidence of anemia in patients with non-Hodgkin's lymphoma receiving the cyclophosphamide, epirubicin, vincristine, prednisone (CEOP) regimen in contrast to patients with Hodgkin's lymphoma treated with the doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) combination. There was a prominent decline in the hemoglobin levels with cisplatin-based combinations in contrast to combinations including noncisplatin agents (p < 0.001). In this study, we have observed equivalent rates of treatment-related anemia when compared with previous data in patients with specific tumor types. The incidence of pretreatment anemia was high in various malignancies. The mechanisms underlying the propensity for a higher risk of pretreatment anemia in patients with malignant disorders and its influence on the outcome has to be elucidated by further population-based and molecular studies.

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.

Clinical outcomes in patients who received lapatinib plus capecitabine combination therapy for HER2-positive breast cancer with brain metastasis and a comparison of survival with those who received trastuzumab-based therapy: a study by the Anatolian Society of Medical Oncology.

PURPOSE: In this study, we investigated the effect of lapatinib plus capecitabine treatment in HER2-positive breast cancer patients with brain metastasis. METHODS: Of 405 metastatic breast cancer patients with brain metastases at referral centers in Turkey, 46 were treated with lapatinib plus capecitabine only after the development of brain metastasis. Patients who only received trastuzumab-based therapy after the development of brain metastases were accepted as the historic control group for survival analyses (n = 65). Patients who received both drugs consecutively or sequentially were excluded from the analyses (n = 34). RESULTS: Median age among 46 patients who received lapatinib plus capecitabine therapy was 45 years (27-76), and median time for development of brain metastases was 11.9 months (0-69 months). Twenty-six out of 38 patients who received lapatinib plus capecitabine and had extracranial metastasis showed partial response or stable diseases (68.4 %). Grade 3-4 toxicity was observed in eight patients (17.3 %). Median overall survival (OS) in patients treated with lapatinib plus capecitabine was significantly increased compared to that in patients treated with trastuzumab-based therapy (19.1 vs. 12 months, respectively, p = 0.039). The incidence of cerebral death was slightly decreased in patients who received lapatinib plus capecitabine compared to those who received trastuzumab-based therapy (32 vs. 43.4 %, p = 0.332). In the multivariate analysis, lapatinib plus capecitabine therapy remained an independent positive predictor for survival [odds ratio (OR), 0.57; p = 0.02]. DISCUSSION: Although this retrospective multicenter study had several limitations, the results suggest that undergoing lapatinib plus capecitabine therapy after the diagnosis of brain metastasis may further improve survival compared to undergoing only trastuzumab-based therapy.

Pathologic and clinical characteristics of elderly patients with breast cancer: a retrospective analysis of a multicenter study (Anatolian Society of Medical Oncology).

There is very little information about breast cancer characteristics, treatment choices, and survival among elderly patients. The purpose of this multicenter retrospective study was to examine the clinical, pathologic, and biologic characteristics of 620 breast cancer patients age 70 years or older. Between June 1991 and May 2012, 620 patients with breast cancer, recruited from 16 institutions, were enrolled in the retrospective study. Patients had smaller tumors at diagnosis; only 15% of patients had tumors larger than 5 cm. The number of patients who had no axillary lymph node involvement was 203 (32.7%). Ninety-three patients (15.0%) had metastatic disease at diagnosis. Patients were characterized by a higher fraction of pure lobular carcinomas (75.3%). The tumors of the elderly patients were also more frequently estrogen receptor (ER) positive (75.2%) and progesterone receptor (PR) positive (67.3%). The local and systemic therapies for breast cancer differed according to age. An association between age and overall survival has not been demonstrated in elderly patients with breast cancer. In conclusion, the biologic behavior of older patients with breast cancer differs from younger patients, and older patients receive different treatments.

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.

Prognostic factors for lymph node negative stage I and IIA non-small cell lung cancer: multicenter experiences.

BACKGROUND: Surgery is the only curative treatment for operable non-small lung cancer (NSCLC) and the importance of adjuvant chemotherapy for stage IB patients is unclear. Herein, we evaluated prognostic factors for survival and factors related with adjuvant treatment decisions for stage I and IIA NSCLC patients without lymph node metastasis. MATERIALS AND METHODS: We retrospectively analyzed 302 patients who had undergone curative surgery for prognostic factors regarding survival and clinicopathological factors related to adjuvant chemotherapy. RESULTS: Nearly 90% of the patients underwent lobectomy or pneumonectomy with mediastinal lymph node resection. For the others, wedge resection were performed. The patients were diagnosed as stage IA in 35%, IB in 49% and IIA in 17%. Histopathological type (p=0.02), tumor diameter (p=0.01) and stage (p<0.001) were found to be related to adjuvant chemotherapy decisions, while operation type, lypmhovascular invasion (LVI), grade and the presence of recurrence were important factors in predicting overall survival (OS), and operation type, tumor size greater than 4 cm, T stage, LVI, and visceral pleural invasion were related with disease free survival (DFS). Multivariate analysis showed operation type (p<0.001, hazard ratio (HR):1.91) and the presence of recurrence (p<0.001, HR:0.007) were independent prognostic factors for OS, as well visceral pleural invasion (p=0.01, HR:0.57) and LVI (p=0.004, HR:0.57) for DFS. CONCLUSIONS: Although adjuvant chemotherapy is standard for early stage lymph node positive NSCLC, it has less clear importance in stage I and IIA patients without lymph node metastasis.