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.

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.

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.

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.

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.

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.

Salvage treatment experience in advanced synovial sarcoma: a multicenter retrospective analysis of the Anatolian society of medical oncology.

BACKGROUND: We aimed to evaluate prognostic factors and response rates to various treatment approaches to patients with synovial sarcoma in an advanced setting. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 55 patients (18 pts; 32.7% women) diagnosed with synovial sarcomas. Twenty had metastatic disease at the time of diagnosis while the remainder of the study group consisted of patients who developed metastatic or inoperable locally advanced disease during follow up. RESULTS: The median follow up time was 15 months (range: 1-53). Regarding outcomes for the 55 patients, 3 and 5 year overall survival rates were 26% and 14%, respectively. In univariate analyses among demographic factors female gender was associated with a better outcome (p=0.030). Patients with early progressing disease (<2 years) had a worse prognosis when compared to patient group with late relapse, but this difference did not reach statistical significance (p=0.056). According to multivariate Cox regression analysis patients who had undergone metastasectomy had a significant survival advantage (p=0.044). The overall response rate to different salvage chemotherapy regimens given as second line treatment was around 42.9-53.9% for all regimes. There were no statistically significant differences between chemotherapy regimens given in either second or third line settings in terms of overall survival. CONCLUSIONS: We observed no major differences in terms of response rate and survival between different salvage chemotherapy regimens. Although metastatic disease still carries a poor prognosis, metastasectomy was found to be associated with improved survival.

Is lymph node ratio prognostic factor for survival in elderly patients with node positive breast cancer? The Anatolian Society of Medical Oncology.

UNLABELLED: Several studies have now demonstrated that the lymph node ratio (LNR), as a superior indicator of axillary tumor burden to the number of excised nodes. While, about the prognostic value of LNR on the the survival of elderly patients is limited. The aim of this retrospective multicenter study is to evaluate the prognostic value of lymph node ratio in elderly patients with node positive breast cancer. METHODS: Onehundredeightyfour patient with operable breast cancer, recruited from 17 institutions, were enrolled into the retrospectively study. Eleven potential prognostic variables were chosen for analysis in this study. Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. RESULT: Among the eleven variables of univariate analysis, four variables were identified to have prognostic significance for Overall survival (OS): pathologic tumor size (T), No. of positive nodes (N), LNR and estrogen receptor-positive (ER). Among the eleven variables of univariate analysis, two variables were identified to have prognostic significance for Disease-free survival (DFS): N and LNR. Multivariate analysis by Cox proportional hazard model showed that T, LNR and ER were considered independent prognostic factors for OS. Furthermore, LNR was considered independent prognostic factors for DFS. CONCLUSION: In conclusion, the LNR was associated with the prognostic importance for DFS and OS in elderly patients who were administered adjuvant 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.

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.

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.

Weekly topotecan for recurrent small cell lung cancer - a retrospective Anatolian Medical Oncology Group study.

AIM: To evaluate efficacy and tolerability of topotecan treatment for recurrent small cell lung carcinoma. PATIENTS AND METHODS: A total of 62 patients were evaluated retrospectively. Statistical analysis was performed using GraphPad Instat (version 3.05). RESULTS: Fifty five patients (89%) were male and 7 (11%) were female. Median age was 56.7 ± 9.3 (34-75). Forty eight of patients (80%) were extensive stage (ES) at the time of diagnosis. Fifty of the patients (80.6 Medical Oncology Clinic) were given median 5.36 cycles of cisplatin-etoposide (2-8 cycles). Time to recurrence was 15.6 ± 6.13 weeks in patients with limited stage (LS) and 6.3 ± 3.82 weeks in extensive stage (ES) (p<0.0001). Overall survival was 14.0 ± 6.08 months in ES and 17.9 ± 6.88 months in LS. The difference between two groups was statistically meaningful (p=0.0447). The overall survival of the patients was 14.8 ± 6.43 months (4.5-40 months). In terms of survival, there was no difference between males and females (p=0.1171). In 17 (27%) patients who were refractory to topotecan or in whom progression occurred other chemotherapies were used. CONCLUSION: Small cell lung cancer is chemosensitive, but recurrences occur in short time. Other chemotherapy regimens are used in progression. Topotecan is one of them. Patients who were young and in whom recurrences occur late had given better response to topotecan. Because of the retrospective nature of the study, we couldn't reach the records exactly and consequently, rate and duration of response couldn't be calculated. In recurrent SCLC topotecan is one of the treatment choices. But both hematological and non hematological side effects should be taken into consideration.

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.

Efficacy and toxicity of gemcitabine plus docetaxel combination as a second line therapy for patients with advanced stage soft tissue sarcoma.

PURPOSE: To assess the safety and efficacy of a gemcitabine plus docetaxel regimen as a second line therapy for patients with advanced soft tissue sarcoma (STS) resistant to doxorubicin and ifosfamide-based therapy. PATIENTS AND METHODS: Medical records of 64 patients with advanced STS who received gemcitabine plus docetaxel regimen as a second line treatment between May 2006 and June 2011 were examined. All patients had been previously treated with doxorubicin plus ifosfamide-based regimen at first line setting. Patients received gemcitabine 900 mg/m2 on days one and eight intravenously over 90 minutes, followed by docetaxel 75 mg/m2 on day eight intravenously over one hour. Cycles were repeated every 3 weeks. RESULTS: The male-to-female ratio was 37/27 and the median age was 44 years (range; 19-67 years). Objective responses were observed in 13 (20.3%) patients (2 CR, 11 PR) and stable disease in 21 (32.8%). Total clinical benefit (CR+PR+SD) was observed in 34 (53.1%). Median overall survival (OS) was 18 months (95% confidence interval (CI):12.1-23.9) and Median time to progression (TTP) was 4.8 months (95% CI: 3.6-6). A total of 243 cycles of chemotherapy were administered. The median number of cycle was 3 (range; 1-11). The most common grade 3-4 hematologic toxicity was neutropenia (35.9%). The most common nonhematologic toxicities consisted of nausea/vomiting (37.5%), mucositis (32.8%), peripheral neuropathy (29.7%), and fatigue (26%). There was no toxicity-related death. CONCLUSION: The combination of gemcitabine plus docetaxel is an active and tolerable regimen as a second line therapy for patients with advanced soft tissue sarcoma who have failed doxorubicin and ifosfamide-based therapy.

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.

Efficacy and toxicity of gemcitabine and pegylated liposomal Doxorubicin in recurrent platinum-resistant/refractory epithelial ovarian cancer.

BACKGROUND: Treatment of patients with platinum resistant/refractory ovarian cancer is a significant problem. In this study, we evaluated the efficacy and tolerability of the combination of gemcitabine and pegylated liposomal doxorubicin (PLD) in patients with platinum resistant/refractory ovarian cancer. PATIENTS AND METHODS: We retrospectively evaluated the activity and toxicity of gemcitabine and PLD combination in 35 patients with recurrent platinum resistant/refractory ovarian cancer who had been treated and followed up in 7 centers in Turkey between December 2005 and June 2008. The patients received gemcitabine 1.000 mg/m(2) on day 1 and 8, and PLD 25 mg/m(2) on day 1 every 28 days. RESULTS: A total of 187 cycles (median, 6 cycles) were delivered. An objective response rate of 28,6 % (1 complete, 9 partial response) was achieved. Additionally, 16 patients (45.7 %) had disease stabilization. The median time-to-progression was 6 months (95 % confidence interval, 4-8) and the median overall survival was 17 months (95 % confidence interval, 12-22). Grade 3-4 hematologic toxicities were as follows: leucopenia (14.3%), neutropenia (8.6%), and anemia (2.9%). One febrile neutropenic episode (2.9%) was observed. Non-hematologic toxicity was well tolerated and easily managed and no grade 3-4 palmoplantar erytrodysestesia (PPE) was observed. CONCLUSION: The combination of gemcitabine and PLD is an effective and tolerable treatment option, with 74.3 % disease control rate for patients with platinum resistant/refractory ovarian cancer.

Retroperitoneal extragonadal nonseminomatous germ cell tumor with synchronous orbital metastasis.

A huge retroperitoneal tumor with a right orbital mass was detected and proved to be an extragonadal nonseminomatous germ cell tumor on biopsy. BEP chemotherapy caused some regression in orbital mass however no change in retroperitoneal tumor size as well as serum tumor marker levels occurred. Herein, we present a rarely seen entity of extragonadal retroperitoneal nonseminomatous germ cell tumor with synchronous orbital metastases and discuss its diagnosis and management.