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We aimed to compare FOLFIRI and bevacizumab with FOLFIRI and aflibercept in terms of overall survival (OS), progression-free survival (PFS) and safety in patients with RAS-mutant metastatic colon cancer who progressed after first-line FOLFOX or XELOX and bevacizumab treatment. This retrospective study included 243 patients from 15 different centres in Turkey. The endpoints of the study were OS, PFS and safety and side effect outcomes. The median age of the patients included in the study was 60 (21-85) years. Of the patients enrolled in the study, 114 patients (46.9%) received aflibercept and 129 patients (53.1%) received bevacizumab. Median OS was 11.2 (95% CI: 9.1-13.2) months in patients receiving FOLFIRI + aflibercept and 14.1 (95% CI: 11.2-17.1) months in patients receiving FOLFIRI + bevacizumab. The median PFS was 5.7 (95% CI: 4.9-6.5) months in the aflibercept arm and 7.7 (95% CI: 7.1-8.3) months in the bevacizumab arm. Grade 3-4 side effects were observed in 58 (50.9%) patients in the aflibercept arm and 33 (25.6%) patients in the bevacizumab arm. As a result of our study, in patients with metastatic RAS-mutant colon cancer who progressed after first-line oxaliplatin-based doublet chemotherapy and bevacizumab, better OS and PFS results were obtained in patients receiving bevacizumab with FOLFIRI compared to patients receiving aflibercept with FOLFIRI. In addition, the side effect profile was more tolerable in the bevacizumab arm., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: Ethical approval was obtained for the multicentric study from Ankara Bilkent City Hospital’s Clinical Research Ethics Committee (Date: 03.07.2024 / No:24–349). All methods were performed in accordance with the relevant guidelines and regulations for this approval. Our Hospital’s Clinical Research Ethics Committee decided that informed consent is waived due to retrospective study design., (© 2024. The Author(s).)

Loss of human epidermal growth factor receptor 2 (HER2) expression can be seen in almost 25-30 % patients after HER2 receptor directed neoadjuvant treatment. These patients have unclear clinical outcomes in previous studies. We aimed to investigate the importance of HER2 loss, additionally with predictive factors for the loss of HER2. This was a retrospective and multicenter study that included 272 HER2-positive BC patients with no pathological complete response who received neoadjuvant chemotherapy plus HER2-targeted treatments. The factors that may affect the loss of HER2 detected by immunohistochemistry(IHC) and the association with survival were analyzed.The rate of HER2 loss after neoadjuvant treatments(NAT) was 27.9 % (n = 76). Disease recurrence was observed in 18(23.7 %) patients with HER2 loss, while it was detected in 62 (31.7 %) patients without HER2 loss(p = 0.23). Pre and post-NAT ER status, and post-NAT ki-67 status had a significant impact on disease-free survival(DFS) (p = 0.0012, p = 0.004, and p = 0.04, respectively).There were no significant association between DFS and loss of HER2 (p = 0.64) and dual anti-HER2 blockade (p = 0.21). Pre-NAT clinical stage (HR:1.65 p = 0.013), post-NAT LN status (HR:3.18, p = 0.02) and pre-NAT ER status (HR:0.24, p = 0.041) were significant independent prognostic factors for DFS while post-NAT residual disease in axillar tissue was an independent prognostic factor for OS (HR:1.54 p = 0.019). Moreover, age (<40 years vs ≥40 years) (p = 0.031) and tumor grade (p = 0.004) were predictive factors for HER2 loss. Our results showed that HER2 loss did not affect survivals. However, young age and being high grade tumor may predict HER2 loss., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Neratinib is an irreversible, pan-HER tyrosine kinase inhibitor that is FDA approved for HER2-overexpressing/amplified (HER2 + ) breast cancer. In this preclinical study, we explored the efficacy of neratinib in combination with inhibitors of downstream signaling in HER2 + cancers in vitro and in vivo ., Experimental Design: Cell viability, colony formation assays, and Western blotting were used to determine the effect of neratinib in vitro . In vivo efficacy was assessed with patient-derived xenografts (PDX): two breast, two colorectal, and one esophageal cancer (with HER2 mutations). Four PDXs were derived from patients who received previous HER2-targeted therapy. Proteomics were assessed through reverse phase protein arrays and network-level adaptive responses were assessed through Target Score algorithm., Results: In HER2 + breast cancer cells, neratinib was synergistic with multiple agents, including mTOR inhibitors everolimus and sapanisertib, MEK inhibitor trametinib, CDK4/6 inhibitor palbociclib, and PI3Kα inhibitor alpelisib. We tested efficacy of neratinib with everolimus, trametinib, or palbociclib in five HER2 + PDXs. Neratinib combined with everolimus or trametinib led to a 100% increase in median event-free survival (EFS; tumor doubling time) in 25% (1/4) and 60% (3/5) of models, respectively, while neratinib with palbociclib increased EFS in all five models. Network analysis of adaptive responses demonstrated upregulation of EGFR and HER2 signaling in response to CDK4/6, mTOR, and MEK inhibition, possibly providing an explanation for the observed synergies with neratinib., Conclusions: Taken together, our results provide strong preclinical evidence for combining neratinib with CDK4/6, mTOR, and MEK inhibitors for the treatment of HER2 + cancer., (©2021 American Association for Cancer Research.)

Purpose: The optimal chemotherapy regimen for concurrent chemoradiation in locally advanced non-small cell lung cancer (NSCLC) remains unclear. Cisplatin-etoposide regimen related toxicity is high, weekly regimens have been investigating. We aimed to compare the efficacy and safety of different concurrent chemotherapy regimens in the context., Methods: A total of 225 patients with locally advanced, unresectable stage III NSCLC were included. Patients who were treated with weekly docetaxel-platin (DP), paclitaxel-platin (PP) and standard dose etoposide-platin (EP) chemotherapy regimens were selected and divided into groups for the comparison of toxicity, response rate, progression free survival (PFS), and overall survival (OS) times., Results: There was a statistically significant difference between overall response rate of each treatment groups (DP: 96.1%, PP: 94% and EP: 76.7%, p < 0.001). The median PFS time of patients who were treated with DP, PP and EP was 16, 15 and 13.3 months, respectively (p = 0.435). The median OS time of patients treated with DP, PP and EP was 19.2, 29.7 and 28.3 months, respectively (p < 0.001). The rates of adverse events such as nausea, vomiting, neuropathy and anaphylaxis was similar. Grade 1-2 mucositis or esophagitis, anemia, pneumonitis were significantly higher in PP group than other groups. However, hematologic toxicities were higher in the EP group than other groups., Conclusions: Compared to the weekly chemotherapy regimens with the standard dose, our study demonstrated similar PFS, but a prolonged OS with the EP regimen. The clinical response rate of weekly regimens was better than the full-dose regimen. Adverse events and toxicity rates were different and depended on the type of chemotherapy regimen used.

Background: To investigate the detrimental effects of prolonged overall radiotherapy duration (ORTD) on survival outcomes of stage IIIB/C NSCLC patients treated with concurrent chemoradiotherapy (C-CRT)., Methods: The study cohort consisted of 956 patients who underwent C-CRT for stage IIIB/C NSCLC. Primary endpoint was the association between the ORTD and overall survival (OS) with locoregional progression-free survival (LRPFS) and PFS comprising the secondary endpoints. Receiver operating characteristic (ROC) curve analysis was utilized for accessibility of the cut-off that interacts with survival outcomes. Multivariate Cox model was utilized to identify the independent associates of survival outcomes., Results: The ROC curve analysis exhibited significance at 49 days of ORTD cut-off that dichotomized patients into ORTD<50 versus ORTD≥50 days groups for OS [area under the curve (AUC): 82.8%; sensitivity: 81.1%; specificity: 74.8%], LRPFS (AUC: 91.9%; sensitivity: 90.6%; specificity: 76.3%), and PFS (AUC: 76.1%; sensitivity: 72.4%; specificity: 68.2%), respectively. Accordingly, ORTD≥50 days group had significantly shorter median OS (P<0.001), LRPFS (P<0.001), and PFS (P<0.001); and 10-year actuarial locoregional control (P<0.001) and distant metastases-free (P<0.011) rates than the ORTD<50 days group. The ORTD retained its significant association with survival outcomes at multivariate analyses independent of the other favorable covariates (p<0.001, for OS, LRPFS, and PFS): Stage IIIB disease (versus IIIC), lymph node bulk <2 cm (versus ≥2 cm), and 2-3 chemotherapy cycles (versus 1). The higher sensitivity for LRPFS (90.6%) than PFS (72.4%) on ROC curve analysis suggested the prolonged ORTD-induced decrements in locoregional control rates as the major cause of the poor survival outcomes., Conclusions: Longer ORTD beyond ≥50 days was associated with significantly poorer OS, LRPFS and PFS outcomes, where reduced locoregional control rates appeared to be the main causative., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Advanced gastric cancer has a dismal prognosis. Platin/5-fluorouracil (PF) combination chemotherapy is the main treatment modality for metastatic gastric cancer patients. Third drug addition to PF is a controversial issue. The aim of this study was to evaluate the predictive role of tumor localization and histopathology on choosing three- or two-drug combination regimens., Methods: This study was designed as a hospital-based retrospective observational case-series study. A total of 516 patients with advanced gastric cancer has been treated at eight different oncology centers in Turkey between 2006 and 2016. Laboratory results and demographic data were collected and analyzed., Results: The median patient age was 59 years (range 25-85). Proximal intestinal and distal intestinal cancers were found in 357 (69.2 %) and 159 (30.8 %) patients, respectively. 5-fluorouracil (5FU) and cisplatin (PF) and cisplatin+5FU+docetaxel (PFtax, also known as DCF) were administered to 240 (46.5%) and 276 (53.5%) patients, respectively. Median progression free survival (PFS) was 5.0 (95% CI 4.21-5.29) and 8 months (95% CI 7.22-8.77) for PF and PFtax groups, respectively (p=0.000). When tumor localization was used as stratum in PFS survival, PFtax produced significantly higher PFS rates only in distal intestinal type gastric cancer compared to PF (p=0.000). Median overall survival (OS) was 12 (95% CI 9.8-14.2) and 16 months (95% CI 13.6-18.4) for the PF and PFtax groups, respectively (p=0.01). When tumor localization was used as stratum in OS, PFtax showed significantly higher OS rates only in the distal intestinal type gastric cancer compared to PF (p=0.01) Conclusion: Pathology and tumor location in gastric cancer may affect the outcome. Addition of taxanes as a third drug may significantly increase PFS and OS rates only in distal intestinal type gastric cancer but not in patients with proximal type gastric cancer.

Purpose: To compare the efficacy and adverse effect profiles of the first-line treatment of patients with KRAS wild type metastatic colorectal cancer (CRC) in Turkey who were treated based on regimens including bevacizumab, cetuximab and panitumumab., Methods: This retrospective multicenter observational study involved a total of 238 patients who received chemotherapy in combination with either bevacizumab or cetuximab or panitumumab as first-line therapy for KRAS wild-type metastatic colorectal cancer. Patients with full medical records having pathological diagnosis of CRC adenocarcinoma were included in the study. The demographic, laboratory, histopathological and clinical characteristics of the patients were determined, and three groups were compared based on the study variables., Results: The mean age of the entire sample (n=238) was 58±11 years, 64% of which were male. The most frequent tumor localization was the rectum (37%) and G2 was the most common tumor grade (59.7%). About 63% of the patients had metastatic disease at diagnosis, with the most common site of metastasis being lung (14.7%) and liver (52.5%). Overall survival (OS) was 63.9%, while 1-, 3- and 5-year survival rates were 91.7, 56.6 and 36.9%, respectively. The expected mean survival was 49.1 months (95% CI, 42.9-55.3). The 1-, 3- and 5-year progression-free survival (PFS) rates following first-line treatment were 65.3, 26.1 and 5.6%, respectively, while disease free survival (DFS) in patients without metastasis at diagnosis was 68.5%. An analysis carried out disregarding which treatment the patients received (FOLFOX or FOLFIRI) revealed that a panitumumab-containing combination resulted in poorer prognosis compared to bevacizumab or cetuximab-containing combination (p<0.001). With regard to the adverse effect profile, the most common adverse effects were neuropathy and neutropenia in patients receiving FOLFOX-bevacizumab; neutropenia and perforation in patients receiving FOLFIRI-bevacizumab; rash and pustular infection in patients receiving FOLFIRI-cetuximab; and diarrhea in patients who received FOLFIRI-panitumumab combination., Conclusion: This is the first multicenter study performed in Turkey evaluating the response to treatment and adverse effects in patients with KRAS wild-type metastatic colorectal cancer.

Background: Selinexor (KPT-330) is an oral agent that has been shown to inhibit the nuclear exporter XPO1. Given the pressing need for novel therapies for triple-negative breast cancer (TNBC), we sought to determine the antitumor effects of selinexor in vitro and in vivo., Methods: Twenty-six breast cancer cell lines of different breast cancer subtypes were treated with selinexor in vitro. Cell proliferation assays were used to measure the half-maximal inhibitory concentration (IC 50 ) and to test the effects in combination with chemotherapy. In vivo efficacy was tested both as a single agent and in combination therapy in TNBC patient-derived xenografts (PDXs)., Results: Selinexor demonstrated growth inhibition in all 14 TNBC cell lines tested; TNBC cell lines were more sensitive to selinexor (median IC 50 44 nM, range 11 to 550 nM) than were estrogen receptor (ER)-positive breast cancer cell lines (median IC 50  > 1000 nM, range 40 to >1000 nM; P = 0.017). In multiple TNBC cell lines, selinexor was synergistic with paclitaxel, carboplatin, eribulin, and doxorubicin in vitro. Selinexor as a single agent reduced tumor growth in vivo in four of five different TNBC PDX models, with a median tumor growth inhibition ratio (T/C: treatment/control) of 42% (range 31 to 73%) and demonstrated greater antitumor efficacy in combination with paclitaxel or eribulin (average T/C ratios of 27% and 12%, respectively)., Conclusions: Collectively, these findings strongly suggest that selinexor is a promising therapeutic agent for TNBC as a single agent and in combination with standard chemotherapy.

Purpose: To evaluate the efficacy and adverse events with cetuximab plus FOLFOX administered as second- and third-line therapy in metastatic colorectal cancer (mCRC) patients., Methods: IPatients were administered cetuximab plus FOLFOX as second- and third-line therapy from January 2010 through October 2015. mCRC patients with wild type KRAS were alsï given irinïtecan and/ïr ïxaliplatin cïmbined with fluorïpyrimidine±bevacizumab. Tumor respïnse and survival were evaluated using RECIST and Kaplan-Meier methïd respectively., Results: Sixty patients were included this study. Cetuximab plus FOLFOX was administered to 40 (66.7%) patients as second-line and to 20 (33.3%) as third-line therapy. The majority of the patients had a good ECOG performance status (PS) (0 or 1). Clinical benefit was partial plus stable disease and it was 75.0% for both of these two lines. The median progression free survival (PFS) was 7.1 months (95% CI=3.2-10.9) and 6.0 months (95% CI=2.4-9.6), in the second-and third-line (p=0.484). The median ïverall survival (ÏS) was 14.3 and 9.2 mïnths in secïnd-and third-line therapy respectively (p=0.071). The common toxicities were haematologic and gastrointestinal, mostly grade 1 and 2., Conclusion: The addition of cetuximab to FOLFOX was well-tolerated and had antitumor activity both in second- and third-line therapy in patients with mCRC.

In previous studies we demonstrated that targeting the nuclear exporter protein exportin-1 (CRM1/XPO1) by a selective inhibitor of nuclear export (SINE) compound is a viable therapeutic strategy against Non-Hodgkin Lymphoma (NHL). Our studies along with pre-clinical work from others led to the evaluation of the lead SINE compound, selinexor, in a phase 1 trial in patients with CLL or NHL (NCT02303392). Continuing our previous work, we studied combinations of selinexor-dexamethasone (DEX) and selinexor-everolimus (EVER) in NHL. Combination of selinexor with DEX or EVER resulted in enhanced cytotoxicity in WSU-DLCL2 and WSU-FSCCL cells which was consistent with enhanced apoptosis. Molecular analysis showed enhancement in the activation of apoptotic signaling and down-regulation of XPO1. This enhancement is consistent with the mechanism of action of these drugs in that both selinexor and DEX antagonize NF-κB (p65) and mTOR (EVER target) is an XPO1 cargo protein. SINE compounds, KPT-251 and KPT-276, showed activities similar to CHOP (cyclophosphamide-hydroxydaunorubicin-oncovin-prednisone) regimen in subcutaneous and disseminated NHL xenograft models in vivo. In both animal models the anti-lymphoma activity of selinexor is enhanced through combination with DEX or EVER. The in vivo activity of selinexor and related SINE compounds relative to 'standard of care' treatment is consistent with the objective responses observed in Phase I NHL patients treated with selinexor. Our pre-clinical data provide a rational basis for testing these combinations in Phase II NHL trials., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Background: For HER2 positive metastatic breast cancer (MBC), continuing anti-HER2 therapy beyond progression is associated with improved outcome. However retreatment with trastuzumab after lapatinib progression is controversial. We retrospectively analyzed the efficacy of trastuzumab-based chemotherapy in HER2+ metastatic breast cancer patients whose disease progressed after lapatinib., Materials and Methods: Between October 2010 and May 2013, 54 patients whose disease progressed after lapatinib were retreated with trastuzumab-based chemotherapy. Efficacy and toxicity results were evaluated retrospectively., Results: The median age of patients was 46 (range 27-67). Fourteen patients (26%) had metastases at the time of diagnosis. All of the patients had received trastuzumab in an adjuvant or metastatic setting, while 16 (30%) had received two lines of trastuzumab. All patients had received lapatinib plus capecitabine. The median chemotherapy line for the metastatic setting was 2 (range 1-7). Cranial metastases were identified in 27 (50%) patients. 53 patients received trastuzumab-based chemotherapy following lapatinib progression while one patient received trastuzumab monotherapy. Combination chemotherapy consisted of navelbin (n=33), taxane (n=10), gemcitabine (n=2), platinum (n=2) and platinum with taxane (n=6). The median treatment cycle was 5 (range 1-44). Among 49 patients assessed for response 2 (4%) showed CR, 12 (25%) PR, 11 (22%) SD and 24 (49%) disease progression. Asymptomatic cardiotoxicity was reported in 2 (4%) of the patients. At a median follow-up of 9 months (1-39), median progression-free survival was 5 months (95% CI 4.1-5.9) and median overall survival was 10 months (95% CI 6.9-13.0). PFS and OS were not affected by the absence/presence of cranial metastases., Conclusions: Retreatment with trastuzumab-based therapy after lapatinib progression showed efficacy in heavily treated MBC patients.

Background: Predictor factors determining complete response to treatment are still not clearly defined. We aimed to evaluate clinicopathological features, risk factors, treatment responses, and survival analysis of patient with advanced nonseminomatous GCTs (NSGCTs)., Materials and Methods: Between November 1999 and September 2011, 140 patients with stage II and III NSGCTs were referred to our institutions and 125 patients with complete clinical data were included in this retrospective study. Four cycles of BEP regimen were applied as a first-line treatment. Salvage chemotherapy and/or high-dose chemotherapy (HDCT) with autologous stem cell transplantation were given in patients who progressed after BEP chemotherapy. Post-chemotherapy surgery was performed in selected patients with incomplete radiographic response and normal tumor markers., Results: The median age was 28 years. For the good, intermediate and poor risk groups, compete response rates (CRR) were, 84.6%, 67.9% and 59.4%, respectively. Extragonadal tumors, stage 3 disease, intermediate and poor risk factors, rete testis invasion were associated with worse outcomes. There were 32 patients (25.6%) with non-CR who were treated with salvage treatment. Thirty-one patients died from GCTs and 94% of them had stage III disease., Conclusions: Even though response rates are high, some patients with GCTs still need salvage treatment and cure cannot be achieved. Non-complete response to platinium-based first-line treatment is a negative prognostic factor. Our study confirmed the need for a prognostic and predictive model and more effective salvage approaches.

Background: XELOX plus bevacizumab (XELOX-Bev) and FOLFIRI plus Bevacizumab (FOLFIRI - Bev) treatments are an effective strategies patients with metastatic colorectal cancer (mCRC).The aim of this study was to compare efficacy of first-line XELOX-Bev treatment vs FOLFIRI-Bev treatment for mCRC., Materials and Methods: A total of 409 patients with mCRC who received chemotherapy were included and divided into 2 groups. Group 1 (n=298) received XELOX-Bev and Group 2 (n=111) FOLFIRI-Bev. Comparisons were made in terms of overall (OS) and progression-free (PFS) survival, response rate (RR), and grade 3-4 toxicity., Results: Median follow-up was 11 months in Group 1 and 15 months for Group 2. Complete remission was observed in 29 (9.7%) and 2 (1.8%) patients, partial remission in 139 (46.6%) and 27 (24.5%) , stable disease in 88 (29.5%) and 49 (44.1%) and progressive disease in 42 (14.1%) and 33 (30.0%) patients in Group 1 and 2, respectively. Median OS was 25 months (range 2-57 months, 95%CI; 22.2-27.7) for Group 1 and 20 months (range 1-67 months, 95%CI; 16.8-23.1) for Group 2 (p=0.036). Median PFS was 9.6 months (range 2-36 months, 95%CI; 8.8-10.4) for Group 1 and 9 months (range 1-44 months, 95%CI; 7.4-10.5) for Group 2 (p=0.019). Objective RR was 56.4% in Group 1 and 26.1% in Group 2 (p<0.001)., Conclusions: First-line XELOX-Bev is more effective with a better response rate, prolongation of median PFS/OS, and a superior safety profile compared with FOLFIRI-Bev.

Eight-year-old girl was admitted to our clinic with the complaint of constant epiphora in the right eye. It was reported that this complaint began after the start of chemotherapy with a diagnosis of Acute Lymphoblastic Leukemia (ALL) about 5 years ago. In addition, eyelid ptosis associated with esotropia also occurred during that period. We found that nasolacrimal duct obstruction did not improve with medical treatment but ptosis and esotropia improved with pyridoxine and pyridostigmine treatment during that period. Examination of the eye on admission revealed nasolacrimal duct obstruction on the right side. Other ocular findings were normal. Nasolacrimal system obstruction, ptosis and esotropia combination has not been reported previously in patients using systemic drugs or receiving chemotherapy due to ALL.

Introduction: The primary aim of this study is to investigate the effect of change in the expression levels of survivin, glutathione-S-transferase P1 (GSTP1), and topoisomerase 2α (TOP2A) on the response to antracyclin-based and taxane-based neoadjuvant chemotherapy., Methods: This study included 32 locally advanced breast cancer patients. Tumoral expressions of survivin, TOP2A, and GSTP1 in serial biopsy specimens obtained before treatment, after sequential 4 cycles of doxorubicin+cyclophosphomide, and 4 cycles of docetaxel were analyzed by real-time polymerase chain reaction. Survivin expressions were additionally analyzed in serial blood samples., Results: The pathologic complete response (pCR) rate and the overall response rate (clinical complete and partial) were 28% (n=9) and 91% (n=29), respectively. There were no statistically significant correlations between serial TOP2A expression levels and response. There was a nonsignificant trend toward an improved response rate with decreased survivin expression. A significant decrease in the GSTP1 expression level throughout treatment (P=0.014), which was also shown to be significantly correlated with a pCR (P=0.0001), was seen. Downregulation of GSTP1 after 4 cycles of anthracycline-based combination was independently associated with improved progression-free survival (P=0.01)., Conclusions: Downregulation of GSTP1 is a significant predictor of pCR and improved progression-free survival during anthracycline-based and taxane-based neoadjuvant chemotherapy in patients with locally advanced breast cancer.

The pathogenesis of in situ thrombosis in cancer patients is not well known. Possible factors include endothelial damage, decreasing levels of anticoagulant factors and increasing levels of pro-coagulants. In the literature, the incidence of arterial thrombosis in cancer patients is reported to be 3.8%; 5-fluorouracil is mentioned as a rare causative agent, whereas cisplatin is thought to be the most common agent responsible for in situ thrombosis. In this report we present a 43-year-old male patient with bilateral popliteal artery embolism after 5-fluorouracil/cisplatin/taxotare combination chemotheraphy for gastric carcinoma. He had no additional risk factors such as smoking or any persistent organic arterial disease. He had sinus cardiac rhythm on electrocardiography and there were no abnormalities on echocardiography that could have been source of emboli. Surgical thrombectomy was performed with effective anticoagulation. After the operation, our medical oncologist discontinued 5-fluorouracil. At follow up, there was no evidence of thrombosis, with normal vascular flow rate.

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.

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.

Background: Glutamine (Gln) supplementation during concurrent chemoradiotherapy (C-CRT) effectively reduces the incidence and severity of acute radiation-induced esophagitis (RIE). However, there are concerns that Gln might stimulate tumor growth, and therefore negatively impact the outcomes of anticancer treatment. We retrospectively investigated the effect of co-administration of oral Gln during C-CRT on survival outcomes of patients with stage IIIB non-small cell lung carcinoma (NSCLC). We additionally evaluated role of oral Gln in preventing C-CRT-induced weight change, acute and late toxicities., Methods: The study included 104 patients: 56 (53.8%) received prophylactic powdered Gln (Gln+) orally at a dose of 10 g/8 h and 48 (46.2%) did not receive Gln (Gln-) and served as controls. The prescribed radiation dose to the planning target volume was 66 Gy in 2-Gy fractions. Primary endpoints of progression-free survival (PFS), local/regional progression-free survival (LRPFS), and overall survival (OS) were correlated with status of Gln supplementation., Results: Oral Gln was well tolerated except for mild nausea/vomiting in 14 (25.0%) patients. There was no C-CRT-related acute or late grade 4-5 toxicity. Administration of Gln was associated with a decrease in the incidence of grade 3 acute radiation-induced esophagitis (RIE) (7.2% vs. 16.7% for Gln+ vs. Gln-; p=0.02) and late-RIE (0% vs. 6.3%; p=0.06), a reduced need for unplanned treatment breaks (7.1% vs. 20.8%; p=0.04), and reduced incidence of weight loss (44.6% vs. 72.9%; p=0.002). At a median follow-up of 24.2 months (range 9.2-34.4) the median OS, LRPFS, and PFS for Gln+ vs. Gln- cohorts were 21.4 vs. 20.4 (p=0.35), 14.2 vs.11.3 (p=0.16), and 10.2 vs. 9.0 months (p=0.11), respectively., Conclusion: In our study, supplementation with Gln during C-CRT had no detectable negative impact on tumor control and survival outcomes in patients with Stage IIIB NSCLC. Furthermore, Gln appeared to have a beneficial effect with respect to prevention of weight loss and unplanned treatment delays, and reduced the severity and incidence of acute- and late-RIE.

Background/aims: The aims of this study were to report the clinical outcomes of adjuvant chemo-radiotherapy after curative resection in 637 patients with gastric cancer., Methodology: The retrospective analysis included 637 patients with resectable gastric cancer and stage IB-IV (M0) from 8 medical centers between 2003 and 2010. The patients were treated with 5FU-leucovorin and radiotherapy according to Schema for INT-0116., Results: Of the 637 patients, the median of overall survival (OS) was 43.7 months and relapse free survival (RFS) was 36.6 months. OS rates were 84%, 45%, 40% while RFS rates were 81%, 45% and 35% at 1, 3 and 5-years, respectively. Hematological and gastrointestinal toxicities (grade 1-4) were observed in 35% and 36.5% of patients, respectively. In univariate analysis, according to the Lauren classification, tumor grade, T stage, N stage, type of operation (total gastrectomy or subtotal) and surgery resection margin (R0 or R1) were found as prognostic factors on RFS and OS (p<0.05). In multivariate analysis, T stage, N stage and surgical margins were found as effective factors on OS. T stage, N stage and Lauren classification were factors affecting RFS., Conclusions: Adjuvant chemo-radiotherapy after curative resection of gastric cancer was feasible, with acceptable toxicities in the Turkish population.

There is no established standard salvage chemotherapy in the second-line setting for patients with advanced gastric cancer (AGC) pre-treated with platinum and taxane-based chemotherapy. Our study aims to evaluate the safety and efficacy of FOLFIRI regimen (irinotecan with leucovorin and bolus and continuous infusion with 5-fluorouracil) as a salvage chemotherapy regimen in patients with AGC. Medical records of 97 patients with AGC who received second-line FOLFIRI regimen between March 2006 and February 2011 were examined. Complete and partial responses were observed in 3 (3.1%) and 23 (23.7%) patients, respectively. The median time to progression (TTP) was 3.5 months (95% CI: 2.4-4.6) and the median overall survival (OS) was 10.5 months (95% CI: 8.8-12.2). The most common observed grade 3/4 toxicities were neutropenia (23.7%), diarrhea (6.2%), and stomatitis (5.2%). FOLFIRI regimen is safe and effective in the second-line treatment of AGC patients pre-treated with cisplatin and taxanes.

Purpose: To determine the characteristics and outcome of patients with refractory gestational trophoblastic neoplasia (GTN) after primary chemotherapy (CTx)., Methods: The outcome of low- and high-risk patients with refractory GTN (n = 14, 37%) was compared to those with non-refractory GTN (n = 24, 63%). Methotrexate treatment was used for patients with low-risk disease and EMA/CO for patients with high-risk disease., Results: Median follow-up time was 53 months (range 1-173 months). All non-refractory patients and 11 refractory patients (79%) survived (p = 0.015). Factors related to resistance to primary CTx was age (p = 0.012), duration between causal pregnancy and initial treatment (p = 0.003), surgery (p = 0.014), hCG level before CTx (p = 0.09) and half-life of hCG (p = 0.061). Six out of 10 low-risk refractory patients treated with EMA/CO regimen in the second-line setting had been followed by no evidence of disease. Nine of 38 (24%) patients underwent surgery (TAH ± BSO) for GTN. All of the patients treated with surgery were in the non-refractory group, but none of refractory patients underwent surgery (p = 0.014)., Conclusions: Surgery and EMA/CO regimen are one of the main factors that play a role in the management of refractory low-risk GTN.

Purpose: Although there are many non-pharmacological practices being recommended for symptom management, most patients prefer to use pharmacological interventions. This study assesses the non-pharmacological interventions used by cancer patients for symptom management during chemotherapy and the factors affecting its use., Method: This study was conducted at the Istanbul University Institute of Oncology, Turkey, with 202 patients. Personal characteristics, illness-related characteristics, symptom severity and non-pharmacological interventions used by the patients were assessed by using Patient Description Form, ECOG and Nightingale Symptom Assessment Scale., Results: Most of the patients in this study were living in Istanbul, 58.4% were women, 78.7% were married and their mean age was 48.82 ± 1.44. Most of the patients experienced different symptoms related to chemotherapy, but only a small number of patients preferred to use and benefited from the non-pharmacological interventions in their symptom management. There were different factors affecting the well-being of the patients, but only being young was found to be an important variable in the use of psychological interventions (OR 3.06 [95% CI 1.17-7.96])., Conclusions: Physicians remain the central figure in the treatment of cancer patients, so oncologists and oncology nurses should be more proactive and innovative in their patient care, education, and counseling to maximize the use of non-pharmacological interventions that may be helpful in symptom management. Further research evaluating the use and effectiveness of non-pharmacological interventions on symptom management in cancer patients is needed., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objective: Patients with breast cancer with a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) have a better prognosis than patients with residual disease. The aim of the current study was to identify predictors of pCR., Methods: This retrospective study included 388 patients treated with anthracycline-based NAC. Clinicopathological parameters were compared between the patients with and without pCR in breast and axilla., Results: Treatment consisted of FAC/FEC in 230 patients (59%), TAC in 39 (10%) patients and AC followed by docetaxel in 119 (31%). In all, 36 (9.3%) patients had pCR. In univariate analysis, age, tumor size, lymph node involvement, tumor grade (p = 0.077, n = 265), ER and HER-2 status (n = 213), lymphovascular invasion (LVI), type of chemotherapy and taxane-containing chemotherapy were associated with pCR. In multivariate analysis, ER negativity (p = 0.003), the absence of LVI (p = 0.009) and taxane-containing NAC (p = 0.026) were found to be significant indicators of pCR. Median follow-up time was 69 months. Progression-free survival was significantly improved in patients achieving pCR (p = 0.001)., Conclusions: pCR is associated with a better outcome regardless of clinical and pathological parameters in breast cancer patients who receive NAC. The probability of pCR was higher in ER-negative, LVI-negative tumors and in patients treated with sequential taxane-containing chemotherapy., (Copyright © 2011 S. Karger AG, Basel.)

This paper reports a 43-year-old patient who had a large, mobile, worm-like thrombus in the left main coronary artery after receiving a chemotherapy regimen containing cisplatin, bleomycin and etoposide for a nonseminomatous testes tumor. The patient was successfully treated with thrombolytic therapy. Physicians should be aware that thrombotic events may be observed after the administration of certain chemotherapeutic agents, particularly cisplatin.

Objective: To evaluate the clinicopathologic prognostic factors in malignant ovarian germ cell tumors., Methods: We reviewed the medical records of 70 patients treated from 1990 to 2006 at our center. Clinical data including demographics, stage, surgery, chemotherapy, survival, menses status, and fertility were collected from patients' charts., Results: Median age was 22 years (range, 9-68). The histologic subtypes included 36 dysgerminomas, 11 yolk sac tumors, 3 immature teratomas, 1 embryonal carcinomas, and 19 mixed types. The most striking clinicopathologic finding was a history of concomitant immunosuppressant therapy, which was observed in 2 patients. Two patients had contralateral sex-cord tumors at presentation and follow-up. During a median follow-up period of 4.6 years, 11 patients had recurrence. The median time to recurrence was 8 months (6-28 months). Recurrences appeared in the abdominopelvic cavity in 9 out of 11 patients. Only one could be salvaged with second-line chemotherapy. Cumulative survival rate was 97% and 60% in patients with dysgerminoma and nondysgerminoma, respectively. Nondysgerminoma histology and residual tumor after surgery were unfavorable prognostic factors (P < 0.001 and P = 0.015). Fertility-sparing surgery was as effective as radical surgery among all eligible patients. Of patients with known menstrual status, 96% had regular menses. Of the 8 patients who opted for conception among these patients, 7 delivered healthy infants., Conclusions: Nondysgerminomas have an aggressive clinical course. New treatment strategies are needed for eradication of abdominopelvic disease at initial diagnosis and recurrent setting. Occurrence of malignant ovarian germ cell tumors may be associated with immunosuppression in some patients. Sex-cord stromal tumors may present with bilateral involvement. It is possible to maintain fertility after fertility-sparing surgery followed by chemotherapy.

Aims and Background: It has been appreciated for some time that the lack of detection of ovarian cancer at clinical and pathological (second-look laparotomy) evaluation is not synonymous with cure. The goal of this study was to define clinical risk factors for recurrence after complete pathological response to postoperative chemotherapy in patients with epithelial ovarian cancer., Methods: Fifty-seven patients who met the inclusion criteria of our study were evaluated. The characteristics (age, menopausal status, histological subtype, tumor grade, presence of ascites at diagnosis, type of omentectomy, FIGO stage, and residual tumor volume after primary surgery) of patients with and those without tumor recurrence were compared., Results: The median follow-up was 52 months (range, 15-142 months). The overall survival rates of the patients were 100%, 96%, and 87% at 1, 3 and 5 years, respectively. At the time of the study analysis, 21 of 57 (37%) patients had recurrent disease. The median time to recurrence was 16 months. Recurrences were most frequent in the pelvis and abdominal cavity (38%). Age, menopausal status, stage at diagnosis, and residual tumor volume after initial surgery were significantly related to the risk of recurrence in univariate analysis (P = 0.039, 0.038, 0.004, and 0.000, respectively). Residual tumor volume after initial surgery was found to be the only significant independent prognostic factor (P = 0.049, HR: 0.16, 95% CI: 0.02-0.99)., Conclusion: We believe it is necessary to conduct randomized studies on this issue because insight into predictors of recurrence after pathological complete response to postoperative chemotherapy could be used to select patients for trials of consolidation therapy.

Gemcitabine and cisplatin are the active agents in metastatic breast cancer pretreated with anthracycline and/or taxane as a second line treatment. The present study was designed to assess the efficacy and safety of this regimen given biweekly schedule in these patients. Twenty-seven women, median age 57, with metastatic breast cancer previously treated with anthracycline and taxane were eligible for enrollment. Gemcitabine was administered intravenously on days 1 and 15 at a dose of 2,000 mg/m(2) and Cisplatin was given intravenously on day 1 and 15 at a dose of 50 mg/m(2). Treatment cycles were repeated on an outpatient basis every 28 days. Of all 27 evaluable patients, the overall response rate was 26% (7 of 27; 95% CI: 11-46%) with seven all partial responses. The stable diseases were found in 9 (33%) patients. At the time of last follow-up, 11 (41%) of the patients died of their disease progression. The median overall survival duration was 7.4 +/- 2.8 months. The 1-year overall survival rate was 46.9% +/- 12.3. Hematological toxicity was not found as the principal dose-limiting toxicity. Severe (grade III/IV) neutropenia was observed only one (4%) patients. No patient was complicated by febrile neutropenia and G-CSF usage was not performed. Grade III and IV anemia were seen in only 4 (15%) and thrombocytopenia was noted only one (4%) patients. Severe hepatic (n = 2) and renal toxicity (n = 1) were observed and these all recovered completely without complication. Several other severe non-hematological side effects were managed easily. Permanent dose reductions were necessary in 9 (33%) patients and chemotherapy administration was also delayed in 7 (26%) patients because of delayed both hematological and non-hematological toxicity recovery. Treatment was discontinued in one (4%) patient due to severe fatigue and deteriorating performance status. In conclusion, gemcitabine and cisplatin combination therapy with this biweekly schedule and dosage is moderately active and extremely safe in patients with metastatic breast cancer previously treated with anthracycline and taxanes.

Background: Pegylated liposomal doxorubicin (PLD) is the only nonplatinum agent to significantly improve survival in patients with platinum-sensitive recurrent ovarian cancer. The present study was designed to assess the efficacy and safety of PLD plus cisplatin combination therapy in these patients., Methods: Twenty-two women (median age, 57 years) with ovarian cancer that recurred 6 months or more after standard carboplatin and paclitaxel therapy were eligible for enrollment. Cisplatin was administered intravenously as a 60-min infusion on day 1, at a single dose of 60 mg/m(2), and PLD was given intravenously as a 1-h infusion on day 2, at a dose of 50 mg/m(2). Treatment cycles were repeated on an outpatient basis every 28 days., Results: Hematological toxicity was mainly leucopenia/neutropenia, and this was the principal dose-limiting toxicity. Severe (grade III-IV) leucopenia/neutropenia was observed in 7 (32%) and 9 (41%) patients, respectively. Only 2 (9%) patients were complicated by febrile neutropenia. Grade III-IV anemia occurred in only 4 (18%) patients. Severe thrombocytopenia was not noted; only 5 patients (23%) had grade I-II toxicity. NO toxicity in biochemical parameters was noted. Several severe nonhematological adverse effects were managed according to standard protocols and were transient, as well as being well-tolerated. Twenty-one patients were evaluated for response. The overall response rate was 62% (13 of 21; 95% confidence interval [CI], 38%-82%), with four (19%) complete and nine (43%) partial responses. At the time of last follow-up, all of the 22 patients were alive. The median follow-up period was 8.5 months (range, 2 to 22 months)., Conclusion: PLD combined with cisplatin at the schedule and dosage used in this study is an active and safe second-line chemotherapy regimen with acceptable and easily manageable toxicities in women with platinum-sensitive recurrent ovarian cancer.

Purpose: Temozolomide and fotemustine are both active drugs for treating metastatic melanoma. The present study was designed to assess the efficacy and safety of combination therapy with temozolomide + fotemustine in patients with metastatic melanoma., Methods: Forty patients (median age 50.5 and 22 males) with pathologically confirmed, unresectable, AJCO stage IV melanoma were enrolled into the study. The primary endpoints were tumor response and safety. Patients received oral temozolomide 125 mg/m(2) on days 1-7 and intravenous fotemustine 80 mg/m(2) on day 3 every 3 weeks., Results: Fourteen (35%) patients achieved an objective response, including 3 (7.5%) complete and 11 (27.5%) partial responses. Median overall survival time was 6.7 months and 6-month survival rate was 57.4%. Myelosupression, particularly thrombocytopenia, was the primary toxicity., Conclusion: The regimen, temozolomide combined with fotemustine, is an active and moderately safe first-line chemotherapy regimen with acceptable and easily manageable toxicities in patients with metastatic melanoma.

A rare case of primary appendiceal mucinous adenocarcinoma is reported. The presenting signs and symptoms were suggestive of acute appendicitis. An appendectomy was performed resulting in a histological diagnosis of grade 2 mucinous adenocarcinoma of the appendix. The patient was referred to our clinic where he underwent a complementary right hemicolectomy with lymph node dissection. Two of the 17 resected lymph nodes were tumor positive but there was no residual tumor in the hemicolectomy specimen. The patient was staged as T4N1M0 and adjuvant multimodality treatment was planned because he was considered at high risk for local-regional recurrence and distant metastasis. Three cycles of capecitabine 1250 mg/m2 on days 1-14 and oxaliplatin 130 mg/m2 on day 1, every 21 days (CAPOX) were administered, then a total dose of 50.4 Gy external-beam radiation therapy was delivered to the primary tumor region and 45 Gy to the lymphatics, and finally 3 further cycles of the CAPOX regimen were administered. Multimodality treatment was well tolerated by the patient, who is still alive 25 months after the hemicolectomy procedure with no evidence of disease progression.

Background: Angiogenesis is regulated by a balance of both angiogenic inducers and inhibitors. This study was designed to evaluate the effect of both maximum-tolerated doses (MTD) and low-dose metronomic chemotherapy (LDM) on serum vascular endothelial growth factor (VEGF), thrombospondin-1 (TSP1) and VEGFR1 concentrations in patients with advanced nonsmall cell lung cancer., Patients and Methods: Forty consecutive patients with advanced stage nonsmall cell lung cancer were included in this prospective study. Twenty patients received MTD chemotherapy including 75 mg/m2 of cisplatin and 75 mg/m2 of docetaxel on day 1. The LDM treatment consisted of cisplatin 25 mg/m2 and docetaxel 25 mg/m2 were given to other 20 patients on weeks 1, 2 and 3. Serum levels were prospectively measured in serum by ELISA at four times; before chemotherapy and at 1, 2 and 3 weeks following initiation of chemotherapy., Results: The major finding in this study that MTD chemotherapy but not LDM chemotherapy resulted in significant changes in VEGFR1 and TSP1 serum levels. Due to the effect of LDM chemotherapy, we showed no statistically significant change in patients for all serum VEGF, TSP1 and VEGFR1 levels. Similarly, serum VEGF levels did not also change under MTD chemotherapy. The MTD chemotherapy induced significant and long-lasting increase of TSP1 levels and decrease of VEGFR1 levels that persisted for at least 3 weeks after the chemotherapy initiation. No significant correlations were found between serum VEGF and TSP1 levels in cancer patients treated with both LDM and MTD chemotherapy. The circulating angiogenic balance (TSP1/VEGF) is decreased in cancer patients (P=0.039)., Conclusions: The continuous/metronomic chemotherapy may not achieve a more pronounced antiangiogenic effect than MTD-scheduling chemotherapy. Future studies involving a larger number of patients are needed to confirm the present findings.

Background: Both gemcitabine and pegylated liposomal doxorubicin (PLD) are antineoplastic drugs with clinical activity in patients with platinum-resistant ovarian cancer. The present study was designed to assess the efficacy and safety of biweekly scheduled gemcitabine and PLD combination therapy in such patients., Methods: Eighteen women with ovarian cancer that had recurred within 6 months after standard carboplatin and paclitaxel therapy were eligible for enrollment. Gemcitabine 2000 mg/m(2) and PLD 20 mg/m(2) were administered intravenously on days 1 and 15 of a 28-day cycle., Results: Hematological toxicity was mild. No severe (grade III/IV) leucopenia/neutropenia or thrombocytopenia was observed. Severe anemia was seen in only 3 (17%) patients. Several other severe nonhematological adverse effects were well tolerated and easily managed. The overall response rate was 28% (5 of 18; 95% confidence interval [CI], 10%-54%) with 2 (11%) complete and 3 (17%) partial responses. The median overall survival time was 17 months (range, 1 to 25 months). The median survival for patients with clinical benefit including disease response or stabilization was 17 months (range, 3 to 26 months) compared to that of patients with progressive disease, which was 2 months (range, 1 to 11 months; P = 0.04)., Conclusion: A biweekly schedule of gemcitabine combined with PLD is an active and safe chemotherapy regimen with acceptable and easily manageable toxicities in women with recurrent platinum-resistant ovarian cancer.

Objective: To evaluate the clinicopathological prognostic factors and outcome of chemotherapy in ovarian carcinosarcomas., Methods: We reviewed the records of 26 patients treated from 1990 to 2006 at the Oncology Institute of Istanbul University. Clinical data including demographics, stage, surgery, chemotherapy, and survival were collected from patients' charts., Results: All patients underwent initial debulking surgery. Optimal debulking was achieved in 21 (81%) patients. The most striking clinicopathological finding was the high incidence of hemorrhagic ascites (n: 6) which was observed in 60% of the patients with ascites (n: 10). The overall median survival of the patients was 26 months. Residual disease was associated with a decreased overall survival, P=0.04. Median survival (50 months vs 9.7 months, P=0.042) of the patients with early stage disease were longer than the patients with advanced stage. Twenty-two patients received platinum-based combination chemotherapy. There was a trend for increased median survival in the patients who were treated with carboplatin/paclitaxel combination (P=0.066). Although the numbers were insufficient for statistical evaluation, the patients treated with ifosfamide combinations had improved survival (36 months vs 26 months). However, when the patients treated with ifosfamide and carboplatin/paclitaxel combinations were combined, survival was statistically improved compared to the other regimens (36 months vs 9.7 months, P=0.04). Chemotherapy regimens containing doxorubicin or cyclophosphamide were not encouraging. Stage (P=0.02) and adjuvant platinum-based chemotherapy containing either paclitaxel or ifosfamide (P=0.024) remained predictive of outcome in the multivariate analysis., Conclusions: Hemorrhagic ascites can be used in the initial differential diagnosis of ovarian carcinosarcomas. Stage, optimal debulking and type of adjuvant therapy were statistically significant prognostic predictors of ovarian carcinosarcomas. We advise that patients with ovarian carcinosarcomas should be treated by optimal cytoreduction followed by adjuvant platinum/taxan or platinum/ifosfamide combinations.

Background: Topotecan is an active agent for the management of untreated and recurrent extensive-disease small cell lung cancer (ED-SCLC). This study was designed to evaluate the efficacy and safety of a triplet combination with topotecan added to the standard PE regimen in previously untreated patients with ED-SCLC., Materials and Methods: Twenty-one patients (median age 55 years, and 18 male) with chemotherapy-naive ED-SCLC were enrolled into the study. PET treatment consisted of etoposide 80mg/m(2), cisplatin 20mg/m(2) and topotecan 0.75mg/m(2) and all were given intravenously on days 1 to 3 for every 3 weeks., Results: Leucopoenia and/or neutropenia and to a lesser extent thrombocytopenia were the main dose-limiting toxicities. Severe leucopenia/neutropenia were observed in 14 (67%)/12 (57%) patients, and only two (10%) developed febrile neutropenia. Severe thrombocytopenia was observed in 6 (29%) patients and one patient died due to orbital and cerebral haemorrhage. Dose reductions were required in 13 (62%) patients, delays in 8 (38%) patients and early treatment discontinuation in 3 (14%) patients. The overall response rate was 52.6% (95% CI: 28, 9-75.6) with 2 (10.5%) complete and 8 (42.1%) partial responses. The overall median survival time was 6.6 months (range 0.5-16.5 months) and the 6-month overall survival was 65.3%+/-11.7. The overall median survival time of responders was 9.7 months compared to 5.7 months in non-responders (p=0.026)., Conclusion: Topotecan combined with PE regimen with this schedule and dosage does not seem to provide any benefit in terms of response and survival in ED-SCLC patients and does not deserve further studies.

Background: Prognostic factors related to survival in patients with inoperable metastatic or recurrent endometrial carcinoma (MREC) have remained unclear due to lack of clinical trials. The management of these patients is also controversial. This study was performed to compare the efficacy and toxicity profiles of two different systemic therapies (chemotherapy vs hormonal therapy) given for the treatment of patients with MREC and to identify the impact of various prognostic factors on the survival., Methods: Between 1992 and 2004, 44 patients with MREC were admitted to our oncology department. Four cases were excluded from this retrospective study because of lack of data in their charts. Age, presence of other systemic diseases (such as diabetes mellitus, hypertension), histological type, tumor grade, stage, disease-free interval, site of recurrence or metastasis, systemic treatment modality, overall response to treatment, and duration of time to progression were evaluated as prognostic factors. Cox regression analysis was performed for identification of independent prognostic factors and differences between patients characteristics of two treatment groups were calculated by the chi-square or t test., Results: The median follow-up was 18 mo (range 3-113). The overall response rates for chemotherapy and hormonal therapy group were 42% and 41%, respectively (p > 0.05). The median time to progression was 4 mo for the chemotherapy group and 5 mo for the hormonal therapy group (p > 0.05). The median survival after metastasis or recurrence was 11 mo for the chemotherapy group and 16 mo for the hormonal therapy group (p > 0.05). In the group of chemotherapy, grade 3-4 hematologic and nonhematologic toxicities were seen in eight and two, patients, respectively. No grade 3-4 toxicities were noted in patients treated with hormonal therapy. In multivariate analysis, only time to progression (p=0.001) and grade (p=0.04) were the independent prognostic factors on survival after metastasis or recurrence., Conclusion: Histological differentiation and duration of time to progression are predictive factors for survival after metastasis or recurrence in the whole group. The efficacy of two different groups of treatment in these patients appears to be similar. But the chemotherapy may have some disadvantageous in terms of toxicity. This study supports a future randomized prospective trial of hormonal therapy vs chemotherapy in patients with MREC.

The present study was designed to assess the efficacy and safety of combination therapy with temozolomide plus cisplatin in patients with metastatic melanoma. Thirty patients with metastatic melanoma were enrolled. Treatment consisted of intravenous cisplatin (75 mg/m) on day 1 and oral temozolomide (200 mg/m) on days 1 to 5, every 4 weeks. Nine patients (30.0%) achieved an objective response, including two complete (6.7%) and seven partial (23.3%) responses. The median response duration was 161 days. The median progression-free and overall survival times were 72 and 120 days, respectively. Myelosuppression and emesis were the primary toxicities. In conclusion, temozolomide combined with cisplatin is an active and safe first-line chemotherapy regimen with acceptable and easily manageable toxicities in patients with metastatic melanoma.

This study was designed to evaluate the tolerability and therapeutic activity of paclitaxel and carboplatin combination therapy followed by radical thoracic radiotherapy with a concomitant boost technique with concurrent weekly paclitaxel in good performance status of patients with stage IIIA and IIIB non-small cell lung cancer. Patients with newly diagnosed inoperable non-small cell lung cancer received paclitaxel (100 mg/m(2)) as a 1-h infusion on d 1,8,15,28,35, and 42. Carboplatin (area under the curve of 6) was given as a 30-min infusion on d 1 and 28. Radiotherapy commenced on d 49 and was delivered with accelerated fractionation with concomitant boost at 1.8 Gy/fraction/d, 5 d/week and 1.5 Gy/fraction/d to a boost field as a second daily treatment for the last 10 treatment days to 60 Gy/35 fractions/5 wk. During radiation treatment, paclitaxel (60 mg/m(2)) was given as a 1-h infusion once weekly for 5 wk. Twenty-four patients were enrolled in the study. Hematologic toxicities and alopecia were the major acute toxicities during induction chemotherapy; 8.7% of the patients experienced grade 3-4 neutropenia and alopecia. The main acute toxicity of concurrent chemoradiotherapy was esophagitis; grade 3 esophagitis was documented in 23.5% of the patients. No major late toxicity was seen. Overall response rate to the treatment was 65.2%. The median and 1-yr overall-survival rates were 24.9 mo and 63.8%, respectively. The median and 1-yr progression-free survival rates were 9.0 mo and 27.8%, respectively. The main acute toxicities were hematologic toxicity, esophagitis, and alopecia. The response rate and the survival rates achieved with this treatment regimen are particularly noteworthy, especially considering the advanced stage of the patients treated.

Docetaxel has been the only single active agent against chemotherapy-pretreated non-small-cell lung cancer (NSCLC). The purpose of this phase II study was to evaluate the efficacy and safety of docetaxel combined with gemcitabine, another effective drug, in patients with NSCLC previously treated with platinum-based chemotherapy. Thirty-three patients were enrolled. Prior chemotherapy was cisplatin combined with etoposide in 24 patients and vinorelbine in 9 patients. Tumors were sensitive (n = 15), resistant (n = 9), and refractory (n = 9) to front-line chemotherapy. Treatment was docetaxel 85 mg/m(2) on d 1, and gemcitabine 1200 mg/m(2) on d 1 and 8, with cycles repeated every three weeks. Ten patients (30.3%, 95% CI: 15.6-48.7) achieved a partial response and 15 (45.5%) stable disease. Responses were similar frequencies in platinum-sensitive and platinum-resistant/refractory tumors. With a median follow-up period of 5.7 mo (range 1.6-20.0), the median and 6-mo event-free survival were 5.5 mo, 40.6%, respectively. Median and 6-mo overall survival were 7.3 mo and 52.7%. Patients with progressive disease to chemotherapy (p = 0.0008), higher LDH (p = 0.005), and NSE levels (p = 0.03) survived shorter than other patients. In patients refractory to prior chemotherapy, survival was poor as borderline significantly (p = 0.06). The major hematological toxicity was neutropenia. Grade III-IV neutropenia was noted in 14 (42%) patients, with three episodes of febrile neutropenia in 111 cycles. Docetaxel combined with gemcitabine is an active and safe second-line therapy for patients with NSCLC.

Twenty-three patients with inflammatory breast cancer treated with a combined modality approach including anthracycline-based induction chemotherapy-surgery-chemotherapy-radiotherapy were reviewed. Twelve patients (52.2%) received FAC (5-fluorouracil, adriamycin, cyclophosphamide) and 11 patients (47.8%) were treated with FEC (5-fluorouracil, epirubicin, cyclophosphamide) induction chemotherapy for three cycles every 3 weeks. Surgery was followed by the initial chemotherapy or second-line chemotherapy for an additional six cycles to complete nine cycles and radiotherapy, respectively. The median overall survival (OS) time was 27 months and the median disease-free survival (DFS) was 13 months. Furthermore, patients treated with FAC induction chemotherapy have been found to have longer median OS and DFS periods compared to patients with FEC induction chemotherapy in both univariate and multivariate analysis. In conclusion, the superiority of doxorubicin-containing chemotherapy over epirubicin-containing chemotherapy should be established in larger randomized studies and more effective chemotherapeutic agents such as taxans are required for better survival rates in inflammatory breast cancer patients.

Gastric carcinoma remains one of the leading causes of cancer-related death in the world. Clinical studies have revealed that approximately two thirds of the patients seek treatment for early recurrence within the abdominal cavity. The aim of this phase II study was to evaluate the toxicity, feasibility, and efficacy of adjuvant intraperitoneal chemotherapy (IPCT) with cisplatin, mitoxantrone, 5-fluorouracil (5-FU), and folinic acid in patients with stage II-III gastric cancer. Patients with stage II and III gastric cancer aged between 15 and 70 years, after curative resection, with adequate liver, renal, and cardiac function were included in the study. The chemotherapy regimen consisted of cisplatin 60 mg/m2, mitoxantrone 12 mg/m2, 5-FU 600 mg/m2, and folinic acid 60 mg/m2, delivered intraperitoneally, diluted in 2 l normal saline. Intraperitoneal fluid was not drained. Each course of IPCT was repeated every 4 weeks for a total 6 cycles. Thirty-nine patients were enrolled in the study. Twenty-eight of the 39 patients (71.8%) completed six courses of the planned schedule. One patient (2.6%) died after a fourth cycle of IPCT from an undetermined reason. The major nonhematologic toxicity from IPCT was grade I-III nausea and/or vomiting experienced by 27 patients (69.2%). Twenty-four (61.5%) patients reported abdominal discomfort. Median follow-up was 23 (range: 3-105) months. Twenty-five patients (64.1%) were dead. Median disease-free survival and overall survival were 12 (CI 95%; 8.3-15.7 months) and 19 months (CI 95%; 10.5-27.5 months), respectively. The cumulative 5-year disease-free survival and overall survival were 24.7% and 30.7%, respectively. The regimen was generally associated with acceptable toxicity. However, adjuvant IPCT has similar survival rates in comparison to no adjuvant treatment; thus, it cannot be currently recommended outside the context of a clinical trial.

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.

Background: Rotor's syndrome is a rare congenital disorder characterized by functional hyperbilirubinemia. Treatment decision may be challenging in a cancer patient with Rotor's syndrome, since the majority of the antineoplastic agents are metabolized in the liver and excreted via the biliary system. We report the first case of paclitaxel administration in a patient with ovarian cancer and elevated bilirubin levels due to Rotor's syndrome., Case: A 50-year-old woman with Rotor's syndrome had an exploratory laparotomy and was diagnosed to have stage IIIC epithelial ovarian cancer. The baseline serum bilirubin value was 15.3 mg/dL. She was started on a 50% dose of 87.5 mg/m(2) paclitaxel by 3-h infusion plus carboplatin AUC-6. The paclitaxel dose was increased by 25% at consecutive cycles until the standard dose of 175 mg/m(2)/3 h was achieved. Six cycles were administered without any metabolic derangement. The patient was rendered disease free with this treatment., Conclusion: Paclitaxel appears to be safe to administer to cancer patients with functional hyperbilirubinemia., ((c) 2002 Elsevier Science (USA).)