4601 Background: The phase III RECORD-1 trial established everolimus as the only agent proven to benefit patients with metastatic renal cell carcinoma (mRCC) after failure of initial VEGFr-TKI therapy. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, more than doubled median progression-free survival compared with placebo, from 1.9 months to 4.9 months. The REACT (RAD001 Expanded Access Clinical Trial in RCC) study was initiated in order to address an unmet medical need and provide everolimus in advance of regulatory approval and commercial availability to patients with mRCC after failure of initial VEGFr-TKI therapy. Methods: REACT was an open-label, international, expanded-access clinical trial (Clinicaltrials.gov: NCT00655252). Eligible patients had measurable or nonmeasurable mRCC of any histology, were intolerant of, or progressed while on, VEGFr-TKI therapy, had a Karnofsky performance score ≥70%, and had adequate bone marrow, hepatic, and renal function. Patients received everolimus 10 mg/day orally, with dose and schedule modifications allowed for toxicity. The primary objective of REACT was to evaluate the long-term safety of everolimus in patients with mRCC, as determined by the overall incidence of grade 3/4 and serious adverse events (AEs). Tumor response to everolimus was also assessed according to RECIST. Results: A total of 1367 patients from 34 countries were enrolled. Safety findings and tumor responses were consistent with those observed in RECORD-1. The most commonly reported grade 3/4 AEs were anemia (13.4%), fatigue (6.7%), and dyspnea (6.4%), and the most frequent serious AEs were dyspnea (5.0%), pneumonia (4.7%), and anemia (4.1%). Median dose intensity was 10.0 mg/day; relative dose intensity ranged from 0.90 to 1.10 in 68.9% of patients. Conclusions: REACT evaluated the safety and tolerability of everolimus in a broader patient population than the controlled trial RECORD-1. Everolimus was well tolerated, with no new safety issues identified and infrequent dose reductions/interruptions in the majority of patients.

e11042 Background: The RS assay has been shown to quantify the likelihood of distant recurrence and also predict the magnitude of benefit from chemotherapy (CT) in women with estrogen receptor positive, node negative with BC. We planned to examine our experience about the effect of RS on treatment decisions in Turkish early BC patients (pts). METHODS We retrospectively reviewed the medical records of the pts whose tumor (tm) tissue has been sent for RS analysis from 8 different oncology centers. We noted the patient, tm, treatment-related characteristics and demographic information. Oncologists are requested to provide their treatment decision before and after the RS assay. RESULTS We identified 89 cases with a median age of 48 (27-73). Fifty-one pts were premenopausal. Seventy-five pts had breast conserving surgery, 86 pts had SLNB. Sixteen pts had T2 disease, 7 pts had N1 disease, 9 pts had nodal micrometastases. The percentage of grade 1/2/3 tms were 29/57/14% respectively. All tms were ER positive and 5 tms were PR negative by IHC. The number of pts with high, intermediate and low RS was 17, 19 and 53 respectively. So far, all pts are alive without relapse; 23 pts received CT, all pts received adjuvant endocrine therapy (ET) and 77 pts received adjuvant radiotherapy. There has been a change from recommending CT to ET after getting RS in 14 cases (9 pts with low RS and 5 pts with intermediate RS). CONCLUSIONS Overall, RS led to a 28% change on the initial treatment plan, so that 14 patients (%15) were saved from CT. Long-term follow up is necessary to analyze the impact of RS on clinical outcome of our patients. [Table: see text].

e15112 Background: Recent data have shown that cardiotoxicity represents a potentially important side-effect in patients treated with sunitinib. We reviewed cardiac adverse events in patients with metastatic renal cell carcinoma (RCC) who underwent treatment with this agent. Methods: The medical records of 74 patients with metastatic RCC, treated with sunitinib at Institute of Oncology, Istanbul University, were retrospectively reviewed. Sunitnib was administered continuosly at a dose of 37, 5 mg (92% of patients) or 25 mg (8% of patients) daily without interruption as second-line treatment after interferone or as first-line treatment. Baseline echocardiography and ECG were performed. All patients had their blood pressure measured at baseline and mountly at the time of clinic visits. For patients experiencing symptomatic cardiotoxicity, clinical evaluations and laboratory, radiographic and cardiac tests carried out at the time of diagnosis of cardiotoxicity were reviewed in detail. Median follow-up was 12 months. Results: Median age of patients was 58 (26-80) years. Thirty seven (56%) patients have been using at least one type of antihypertensive drugs. Before initiation of sunitinib, history of smoking, hypertension, diabetes mellitus, coronary artery diesase and chronic renal failure, were present in 26 (38%), 27 (37%), 12 (16%), 8 (11%) and 4 (6%) patients respectively. Two patients had myocardial infarction, one patient had long QT syndrome, 2 patients had grade 3 systolic cardiac dysfunction under suntinib treatment. In patients with history of hypertension, hypertensive pulmonary edema (1 patient) and grade 3-4 hypertension (4 patients) occurred. Cardiac tamponade developed in a patient without hypothyroidism and with cytologically confirmed uninvolvement of pericardial effusion. Conclusions: Patients undergoing sunitinib, especially those with a previous history of hypertension and coronary heart disease, are at increased risk for cardiovascular events and should be monitored for exacerbations of their hypertension and for evidence of LVEF dysfunction and myocardial ischemia during treatment.

e15135 Background: The optimal management of stage I nonseminomatous testis cancer varies according to the centers' expertise. Available treatment strategies include close surveillance, retroperito...

e16017 Background: Radiation treatment with concomitant chemotherapy has improved the therapeutic outcome of patients with locally advanced nasopharyngeal carcinoma. However, the importance of neoadjuvant chemotherapy before the definitive therapy is still undefined. We report the results of our experience with neoadjuvant chemotherapy. Methods: Between 2004 and 2008, charts of 59 patients with advanced loco regional nasopharyngeal carcinoma treated in our institute were reviewed. They received induction chemotherapy consisting of cisplatin (75mg/m2) on day 1 and docetaxel (75mg/m2) on day 1 every 3 weeks and followed by definitive radiotherapy and concomitant cisplatin (100mg/m2) every 3 weeks or (40mg/m2) weekly during the radiotherapy. Results: The median age was 49 years 18-68y) and median follow up was 29 months (6-56mo). According to the American Joint Committee on Cancer's 2002 stage classification, all patients were stage II (15%), stage III (63%) and stage IV (22%). Fifty eight patients received 3 cycles of chemotherapy. One patient could not take the full dose chemotherapy due to gastrointestinal toxicity. Except for this patient, there was no grade 3 or 4 toxicity after induction chemotherapy. Concomitant cisplatin with radiation therapy was given to forty nine patients (83%). Of those, thirty two patients received more than 1 cycle of concomitant cisplatin. Grade 3 and/or 4 toxicities after cheomoradiation therapy were mucositis (46%), weight loss (10%), skin toxicity (14%), esophagitis (5%), emesis (5%), neutopenia (5%), thrombocytopenia (3%) and anemia (2%). Fifty one patients (87%) and fifty six (95%) patients achieved an objective response (Complete and partial response) after induction chemotherapy and chemoradiotherapy, respectively. One patient had local relapse alone, 2 patients had both local and distant metastases and 4 patients had distant metastases. Three years overall survival (OS) and disease free survival (DFS) rates were 93% and 83%, respectively. Conclusions: Induction chemotherapy with docetaxel and cisplatin is a feasible and tolerable treatment. No significant financial relationships to disclose.

In Western literature, there are few studies investigating the predictors of early versus late recurrence after curative gastrectomy for gastric cancer. The current study analyzed (1) patients who died of recurrent gastric cancer and (2) prognostic factors, which can be applied to timing of death from tumor recurrence. Of 492 patients who underwent curative resection (R0) for gastric cancer in the Department of Surgery, Medical Faculty of Istanbul between 1994 and 2000, 142 patients who died of recurrence were included into study. None of the patients had received postoperative adjuvant treatment. The patients were divided into 2 groups: an early recurrence group that included 102 patients who recurred and died within 2 years after surgery, and a late recurrence group, which included 40 patients who died of recurrence more than 2 years after surgery. Clinicopathologic findings were compared between the early and late recurrence groups. Multivariate analysis was performed to investigate the independent factors, which are predictive for early versus late recurrence, and prognostic factors independently associated with the survival period. In multivariate analysis, the early recurrence group, when compared with the late recurrence group, was characterized by lymph node metastasis (N1-3 versus N0; P = 0.002). Overall survival was influenced by nodal status (N1-3 versus N0; P = 0.003), type of operation performed (radical total versus radical subtotal gastrectomy; P = 0.003), Eastern Cooperative Oncology Group performance status (PS 3-4 versus PS 1-2; P = 0.004), and tumor localization (cardia versus corpus and antrum; P = 0.046). In contrast, T stage of the disease was not prognostic for survival, although it was close to statistical significance (P = 0.066). Multivariate analysis showed that poorer performance status at initial presentation (P = 0.001) and lymph node metastasis (P = 0.032) independently correlated with overall survival (P = 0.002). Lymph node status was the most important factor predictive for early versus late recurrence and patients with lymph node metastases were at more risk of death within 2 years after curative operation for gastric cancer. Postoperative chemoradiotherapy should be especially recommended for patients at high risk of recurrence of adenocarcinoma of the stomach or who have undergone curative resection.

4733 Background: There is no established standard chemotherapy (CT) regimen for patients with refractory or recurrent germ cell tumors. Method: Thirteen patients with germ cell tumors who were either refractory to prior cisplatin-based chemotherapy (CT) or recurrent disease have been treated with TIP (paclitaxel 175mg/2 given as a 3 hour infusion, ifosfamide 1.2 gr/m2 in 4 hour infusion with mesna for 5 days and cisplatin 20 mg/m2 for 5 days, q3wks) between 2002 and 2003 at Istanbul University Oncology Institute. Results: The median age was 29 (range: 20 - 40). Two patients (15%) had seminomatous and eleven (85%) had non-seminomatous histology. One of 15 patients have extragonadal germ cell tumor. All patients received BEP chemotherapy previously. Among these, four patients were refractory (relapsed while on therapy) to the BEP CT. The remaining group had a median recurrence time of 11 months. Response evaluation was done after 2 or 3 cycles of CT with radiological assessment and tumor markers. At the time of recurrence, 10 patients (77%) had elevation of either AFP or b-hCG. The radiological CR rate after CT was 15%. Despite normalization of tumor markers, two patients had radiological evidence of residual tumor. One patient has been operated for the residual tumor and one of the responding patients undergone autologous stem cell transplantation. Grade III or IV neutropenia was observed in all patients, febrile neutropenia in 7 (54%), and anemia in 7 (54%), and thrombocytopenia in 9 (69%) patients. Dose modification was needed in 7 (54%) patients and a dose delay greater >1 week was done in 8 (62%) patients. Currently 9 patients are alive and the median time to progression (TTP) was 3 months. Conclusion: TIP combination CT failed to yield a favorable outcome in terms of TTP in patients with refractory or recurrent germ cell tumors. No significant financial relationships to disclose.

PURPOSE:To retrospectively analyse the disease-free survival (DFS) and overall survival (OS) according to the International Prognostic Index (IPI) risk groups in patients with aggressive non-Hodgkin's lymphoma (A-NHL) treated at the Institute of Oncology, Istanbul University between 1989-1998. PATIENTS AND METHODS:The records of 201 patients with A-NHL and aged 15 years and over were retrospectively analysed. Features evaluated for potential prognostic importance for DFS and OS included sex, age, tumor stage, performance status (PS), "B" symptoms, bone marrow infiltration, number of extranodal disease sites, size of the largest tumor, histologic grade, erythrocyte sedimentation rate (ESR), and serum levels of lactate dehydrogenase (LDH), albumin and beta2-microglobulin. The International Working Formulation system and the Ann Arbor staging system were used for histologic and staging classifications, respectively. Kaplan-Meier, log-rank and Cox's methods were used for statistical analyses. RESULTS:Sixty-six percent of the patients were classified in the low risk group; 23% in the low-intermediate risk group; 9% in the intermediate-high risk group; and 2% in the high risk group. The median follow-up was 25.9 months (range 1-150 months). Five-year DFS and OS were 41% and 47%, respectively, in all patients. According to IPI, based on the age, tumor stage, LDH level, PS, and extranodal involvement in the identified 4 risk groups of all patients and all ages, the 5-year DFS and OS rates were 66-51%, 49- 43%, 40-34%, and 0%, respectively. Patients in the lowintermediate and intermediate-high risk groups had a worse survival outcome than low risk patients (p=0.001). CONCLUSION:The IPI can be used in the selection of appropriate therapeutic strategy for individual patients. IPI is the most acceptable prognostic system, but being not the ideal one, is still being under critical discussion.

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

The taxanes are the most active new agents for squamous-cell carcinoma of the head and neck (SCCHN) since the discovery of cisplatin. Our aim was to define the therapeutic efficacy and toxicity of paclitaxel and cisplatin combination therapy in patients with recurrent SCCHN. Patients with locally recurrent or metastatic SCCHN were enrolled in the study. Patients were required to be chemotherapy-naive, and should have completed radiation therapy at least 6 weeks prior to enrollment. A World Health Organization (WHO) performance status of less than 3 was required. Paclitaxel (Taxol((R)), Bristol Myers Squibb Company, Princeton, NJ) and cisplatin therapy (PC) consisted of prophylaxis with pheniramine 50 mg i.v., ranitidine 150 mg i.v. and dexamethasone 20 mg i.v. given prior to paclitaxel 175 mg/m(2) as a 3-hour i.v. infusion, followed by cisplatin 75 mg/m(2) as a 1-hour infusion with an additional 3000 cc of saline for hydration. This treatment was repeated every 3 weeks for a maximum of six cycles. Patients were evaluated for response after the third and sixth cycles, or at the time of clinical progression. Fifty patients were enrolled in the study. The overall response rate was 32% with a 10% complete response rate. Forty-eight patients were assessable for toxicity. A total of 221 cycles of chemotherapy was given and the most common toxicity was myelosuppression; 7.7% of cycles had grade III-IV neutropenia. Severe neuropathy, nephropathy, mucositis, and emesis were uncommon (<10%). At a median follow-up period of 25 months, the median overall survival was 10 months and the 1-year progression-free and overall survival rates were 16.7% and 35.2%, respectively.We conclude that patients with recurrent SCCHN have a moderate response to combination chemotherapy with cisplatin and paclitaxel. Given this moderate response rate, it is unlikely that this combination (PC) might ultimately prove to be superior to standard treatment regimens in terms of significant survival advantage.

Extragonadal germ cell tumors are rare neoplasms with histologic features comparable to those of gonadal origin. In this case report we present a 21-year-old female patient with an atypical localization of metastatic gestational choriocarcinoma. She was admitted to our hospital with recurrent epistaxis, abnormal vaginal bleeding, rectal bleeding, subcutaneous nodules on both thighs and forearms and left maxillary mass with intranasal cavity invasion. Laboratory analysis revealed significant elevation in serum beta-human chorionic gonodotropin (beta-HCG) level. Abdominal computerized tomography (CT) revealed left renal and retroperitoneal masses and thoracic CT displayed multiple bilateral lung metastases. Histopathological evaluation of the biopsy specimen obtained from the maxillary sinus showed choriocarcinoma. Based on WHO criteria she was classified as high-risk metastatic choriocarcinoma and treated with combination chemotherapy. We believe that in young women with recurrent epistaxis, gross abnormal vaginal and rectal bleeding and atypical maxillary sinus tumor with multiple lung metastases, choriocarcinoma should be included in the differential diagnosis and previous history of pregnancy or abortion should be obtained.

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

AIM:Undifferentiated nasopharyngeal carcinoma (UNPC) is a chemosensitive tumour; a randomized study evaluating neoadjuvant chemotherapy with bleomycin/epidoxorubicin/cisplatin (BEC) in addition to conventional radiotherapy has resulted in a better disease-free survival in the chemotherapy arm. The bleomycin infusion in the BEC regimen has necessitated hospitalization for the infusion, and resulted in serious pulmonary toxicity. This study has aimed to omit the bleomycin, and test the efficacy and toxicity of cisplatin (C) and a higher dose of epidoxorubicin (EPI) in patients with locally advanced UNPC.METHODS:Seventy-one patients with locally advanced UNPC were treated with three cycles of C 100 mg/m2 day 1, and EPI 100 mg/m2 day 1 every 3 weeks followed by conventional radiotherapy of 70 Gy.RESULTS:Neoadjuvant chemotherapy was well tolerated. There was only 1-week delay in 14.3% of the patients and no dose modification. Grade III-IV neutropenia occurred in 18.9% of the cycles: none of the patients developed neutropenic fever. No patient progressed during chemotherapy, the complete response rate was 26.8% (95% CI = 16.9-38.6) and the partial response rate was 59.1% (95% CI = 46.8-70.7) for an objective response rate of 85.9% (95% CI = 75.6-93.0) at the end of the three cycles of chemotherapy. After the completion of radiotherapy, the complete response rate increased to 81.7% (95% CI = 70.7-89.9) and the objective response increased to 91.5% (95% CI = 82.5-96.8). The median disease-free interval and the median survival have not been reached. The 5-year disease-free and overall survival rates are 53.0% (95% CI = 43.7-62.0) and 57.2% (95% CI = 48.3-65.2), respectively.CONCLUSION:Neoadjuvant C and EPI, easily administered in the outpatient setting, is an effective and well-tolerated regimen in the treatment of locally advanced UNPC.

Epirubicin is an agent with a lower incidence of cardiotoxicity and myelotoxicity compared with doxorubicin; and it is active in patients with non-Hodgkin’s lymphoma (NHL). Our aim was to define the therapeutic efficacy and toxicity of dose-intensified epirubicin in combination with cyclophosphamide, vincristine, and prednisone (CEOP) in patients with diffuse large-cell NHL. Previously untreated patients aged between 15 and 75 years, with at least one measurable lesion, adequate liver, renal, cardiac functions, and no central nervous system involvement were included in the study. The planned chemotherapy regimen CEOP consisted of cyclophosphamide 750 mg/m2, epirubicin 100 mg/m2, and vincristine 1.4 mg/m2 intravenously on day 1 and 100 mg prednisone taken orally on days 1 to 5. Courses were repeated every 21 days. Patients with stage I and II received four cycles of chemotherapy followed by involved-field radiotherapy, and patients with stage III and IV received six cycles of chemotherapy followed by radiotherapy to bulky lymph node sites. Seventy-five patients were enrolled in the study. The complete response rate was 83.8%, and 72 patients were assessable for toxicity. The most common toxicity was myelosuppression; 13.9% of the patients had grade III-IV neutropenia. Severe mucositis, diarrhea, and emesis were uncommon (<10%). At a median follow-up period of 41 months, the 5-year progression-free survival and overall survival rates were 63.5% and 65.3%, respectively. Increasing the dose intensity of epirubicin can yield a similar complete response rate compared with the regimens used in NHL without significantly increasing the toxicity rate associated with chemotherapy. The role of dose-intensive epirubicin should be investigated further in future randomized trials.