Gul Basaran

Taxanes alone or in combination with anthracyclines as first-line therapy of patients with metastatic breast cancer.

PURPOSE Taxanes (paclitaxel or docetaxel) have been sequenced or combined with anthracyclines (doxorubicin or epirubicin) for the first-line treatment of advanced breast cancer. This meta-analysis uses data from all relevant trials to detect any advantages of taxanes in terms of tumor response, progression-free survival (PFS), and survival. PATIENTS AND METHODS Individual patient data were collected on eight randomized combination trials comparing anthracyclines + taxanes (+ cyclophosphamide in one trial) with anthracyclines + cyclophosphamide (+ fluorouracil in four trials), and on three single-agent trials comparing taxanes with anthracyclines. Combination trials included 3,034 patients; single-agent trials included 919 patients. RESULTS Median follow-up of living patients was 43 months, median survival was 19.3 months, and median PFS was 7.1 months. In single-agent trials, response rates were similar in the taxanes (38%) and in the anthracyclines (33%) arms (P = .08). The hazard ratios for taxanes compared with anthracyclines were 1.19 (95% CI, 1.04 to 1.36; P = .011) for PFS and 1.01 (95% CI, 0.88 to 1.16; P = .90) for survival. In combination trials, response rates were 57% (10% complete) in taxane-based combinations and 46% (6% complete) in control arms (P < .001). The hazard ratios for taxane-based combinations compared with control arms were 0.92 (95% CI, 0.85 to 0.99; P = .031) for PFS and 0.95 (95% CI, 0.88 to 1.03; P = .24) for survival. CONCLUSION Taxanes were significantly worse than single-agent anthracyclines in terms of PFS, but not in terms of response rates or survival. Taxane-based combinations were significantly better than anthracycline-based combinations in terms of response rates and PFS, but not in terms of survival.

Vascular endothelial growth factor, hypoxia-inducible factor 1 alpha and CD34 expressions in early-stage gastric tumors: relationship with pathological factors and prognostic impact on survival.

Background: Angiogenesis is one of the key steps in solid tumor growth and metastasis. We planned to investigate the prognostic significance of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α) and CD34 expressions as markers of angiogenesis in gastric cancer. Patients and Methods: We retrospectively reviewed the medical records of 51 gastric cancer patients who had total or subtotal gastrectomy at Marmara University Hospital from 1990 to 2004 and evaluated the expression of VEGF, HIF-1α and CD34 by immunohistochemistry in their archival tumor tissues. We recorded the clinical and pathological characteristics of these patients and analyzed their survival outcome. Results: Thirty out of 51 patients were males. The median age was 63 years (range 34–81). The median follow-up was 17 months. Thirty-six patients had node-positive disease. The majority of patients (n = 43) had T2 and T3 disease. Vascular and lymphatic invasions were present in 57 and 77% of tumors, respectively. VEGF and HIF-1α were positive in 65 and 71% of tumors. The median CD34 staining score was 19 (3–68). VEGF, HIF-1α and CD34 expressions were more frequent in tumors without serosal invasion (p = 0.01, p = 0.01 and p = 0.003, respectively). CD34 expression was significantly more frequent in tumors with VEGF and HIF-1α expression (p = 0.00, p = 0.00). HIF-1α expression was more frequent in tumors with VEGF expression (p = 0.00). The 5-year overall survival was 45%. VEGF, HIF-1α, CD34 expressions and other pathological characteristics were found to have no impact on survival. Conclusion: VEGF, HIF-1α and CD34 expressions were more common in tumors without serosal invasion. As a future perspective, biological agents targeting VEGF and HIF-1α might be more effective at earlier stages of gastric cancer.

The association between individual attachment patterns, the perceived social support, and the psychological well-being of Turkish informal caregivers.

Background: This study aimed to investigate the relations among the psychological well‐being (i.e. depression and state/trait anxiety levels), attachment patterns (i.e. secure, ambivalent, avoidant), and the perceived social support from family/friends/significant others of caregivers of cancer patients in Turkey.

Prolonged interval in prophylactic heparin flushing for maintenance of subcutaneous implanted port care in patients with cancer.

The long-term use of subcutaneous implanted ports for chemotherapy in cancer patients has been associated with the occurrence of thrombosis and infection. In this study, we compared the safety and efficacy of administration of 1000 U of heparin flushes in prolonged interval (every 6 weeks) with standard dose and schedule (500 U every 4 weeks) for port-related infections and thrombosis during periods of non-use. Data were collected retrospectively from patients treated for various cancer types (matched as 2:1 for age, gender, stage of the disease). Patients who had diseases that could cause thrombosis or bleeding in their past medical history, or were taking oral anticoagulants, or had contraindications for heparin usage were excluded. After completing their chemotherapy, 59 patients received prolonged interval, while 30 patients received standard schedule. All patients were followed for at least 1 year. No clinically documented port-related infection or thrombosis has been found in both groups. Also, none of the devices was removed during this time. Prophylactic flushing of central venous ports with 1000 U of heparin in every 6 weeks might be a safe, easy, cheaper, comfortable and effective alternative to standard dose and schedule for preventing thrombosis and infections.

Epithelioid hemangioendothelioma with multiple organ involvement

Epithelioid hemangioendothelioma is a rare vascular neoplasm of uncertain malignant potential. Various reports document metastatic or concurrent epithelioid hemangioendothelioma in several sites, most commonly with combined lung and liver involvement. The concurrent involvement of multiple sites at presentation may cause diagnostic problems because epithelioid hemangioendothelioma can mimic other neoplastic processes. Although it is a chemoresistant disease, chemotherapy is usually advised for patients with metastatic or concurrent involvement. Here we document the presentation, treatment, and outcome of two cases with concurrent involvement of the lung and liver.

Review of the current role of targeted therapies as maintenance therapies in first and second line treatment of epithelial ovarian cancer; In the light of completed trials

Late and recurrent stage ovarian cancer has a high mortality and low response rate to therapy beyond first line treatment. Although first line platinum/taxane based regimens have a satisfactory response rate eventually in most cases disease recurrence is common and second-line treatments are not curative. Delaying progression or recurrence is the main goal of current ongoing clinical studies by means of establishing an effective maintenance regimen with acceptable toxicity profile. Clearly, the persistence of dormant and drug-resistant cells after front-line treatments results in the inability to cure the disease. Over the past several years, the idea of prolongation of therapy for ovarian cancer has garnered clinical attention and academic debate. As a result of a greater understanding of the molecular pathways involved in carcinogenesis and tumor growth, a large number of potential therapeutic targets have been identified and drugs to block receptors, ligands or pathways are being developed. Currently, numerous clinical trials with targeted agents have just been completed or are ongoing involving patients achieving a complete or durable response after first-line and beyond the first line chemotherapy in order to evaluate the efficacy of different therapeutic approaches in terms of progression-free survival and overall survival.

Serum thymidine kinase 1 levels correlates with FDG uptake and prognosis in patients with non small cell lung cancer

Context: TK1 found to be elevated biomarker in many solid cancers. Objectives: The study aimed to assess the prognostic significance of a serum TK1 in patients with metastatic NSCLC. Methods: The study included 48 consecutive patients, newly diagnosed with metastatic NSCLC, and 10 healthy volunteers. Serum TK1 activity determined by ELISA method. Results: Patients with a bTK1 level >156 Du L–1 had significantly shorter survival. TK1 level showed a strong correlation with primary tumor SUVmax. Discussion and conclusion: The magnitude of maximum fluorodeoxyglucose uptake in primary tumors and the serum TK1 level in patients with metastatic NSCLC were found to be independent prognostic predictors of overall survival.

Phase II study of lapatinib in combination with vinorelbine in patients with HER2 positive recurrent or metastatic breast cancer: A multicentric Turkish Oncology Group (TOG) trial

BACKGROUND The aim of this explorative phase II study was to evaluate the activity and safety of lapatinib in combination with intravenous vinorelbine in women with HER2 positive metastatic or recurrent breast cancer. METHODS Twenty-nine patients were enrolled. The primary objectives were response and clinical benefit (CB) rates, secondary objectives were toxicity, response duration and progression free survival. Patients received 1250 mg oral lapatinib continuously once daily and intravenous vinorelbine 20-25 mg/m(2) on days 1 and 8, every 3 weeks. RESULTS Although 25 patients were evaluable for response, according to intend to treat analysis of 28 patients; 14% had confirmed partial response (PR) and 36% had stable disease more than 24 weeks with a CB rate of 50%. Sixty four percent of the patients suffered from grade 3-4 hematologic and 18% from grade 3 extra-hematologic toxicities. CONCLUSION The results of this trial provide evidence to further investigate the potential of this combination for patients unsuitable for trastuzumab or who become refractory to trastuzumab.

Clinical Outcome of Turkish Metastatic Breast Cancer Patients with Currently Available Treatment Modalities - Single Center Experience

BACKGROUND Breast cancer is the most common malignancy and the second leading cause of cancer-related death among women in the developed countries. Despite advances in screening, improved local therapies and adjuvant systemic treatments, median survival of metastatic breast cancer patients (MBC) is in the range of 2-3 years at most. We aimed to investigate whether the prognostic factors and therapeutic responses of our Turkish patients are similar to those in the literature. MATERIALS AND METHODS We reviewed the medical records of MBC patients who had been treated in our institution between 1999-2009 and analyzed their clinicopathological features and survival outcomes retrospectively. RESULTS A hundred and sixty patients were included. Median age was 47 (23-82), median follow up was 24 (2-186) months. At the time of diagnosis 59% of patients were under the age of 50 and 46% were postmenopausal. The majority (37%) had multiple sites of metastases. Forty percent received endocrine therapy and 40% chemotherapy as first line metastatic treatment. Thirty (20%) patients were treated with molecular targeting agents like trastuzumab, lapatinib and sunitinib, frequently combined with a chemotherapy agent. Five-year overall survival (OS) was 32% and median OS was 38 months for the whole group. Five year progression free survival (PFS) was 10% and median PFS was 10 months. Menopausal status, hormone receptor expression and disease free status had a significant impact on overall survival in the multivariate analysis (p 0.018, p 0.018 and p:0.003, respectively). CONCLUSIONS All our patients were treated with the modern oncologic therapies recommended by the international guidelines. From our data, MBC patients live up to 3-4 years, indicating that further improvement beyond that requires development of new treatment modalities. The survival outcomes of our patients were consistent with the data reported in the literature.

Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine Alone in Treatment of Favorable, Limited-Stage Hodgkin's Lymphoma: Do We Really Have Robust Data?

TO THE EDITOR: Canellos et al recently reported that six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) is an effective and safe treatment for favorable, limited-stage Hodgkin’s lymphoma (HL) based on a retrospective review, including 71 patients from a single institution. The European Organisation for Research and Treatment of Cancer H8F trial was the first trial to demonstrate that higher rates of freedom from recurrence may translate into an overall survival (OS) benefit at 10 years. Therefore, in long-term follow-up, the possibility of poorer survival as a result of higher recurrence rates is of concern when chemotherapy (CT) is given alone. Despite this concern, several trials investigated the impact of singlemodality treatment with CT on clinical outcome in an attempt to reduce treatment-related toxicity. Importantly, most trials evaluating CT with or without radiotherapy (RT) had methodologic limitations. The Spanish trial cited in the discussion is a nonrandomized study including stage I, IIA, and IIB patients. The National Cancer Institute of Canada Clinical Trials Group and Eastern Cooperative Oncology Group study compared four to six cycles of ABVD (the number of cycles was response adapted after the first two cycles) with subtotal nodal RT, which is no longer considered as a standard therapeutic option in HL. Patients were stratified into favorableand unfavorable-risk cohorts before random assignment, and ultimately, 276 of 399 patients had unfavorable features. The unfavorable-risk cohort received two cycles of ABVD in addition to subtotal nodal RT. Thus, indeed, the trial compared CT with combined-modality treatment. With a median follow-up of 4.2 years, there was no OS difference between the CT and RT arms. In a subset analysis comparing patients stratified into the unfavorable cohort, freedom from progression (FFP) was superior in patients assigned to combined-modality treatment. It should be noted that FFP was not the primary objective of the trial. The Memorial Sloan-Kettering Cancer Center trial was an underpowered single-institution phase II study including a more heterogeneous group of patients with stages I, IIA, IIB, and IIIA HL that compared six cycles of ABVD with modified extended-field RT. There was an absolute 5% difference in FFP between the groups, with a P value of .08. The authors suggested that a possible significant benefit might be masked by the low number of patients. The Indian trial included patients with all stages of HL and suggested a superior outcome in the combined treatment arm compared with the CTalone arm in the overall analysis, with a median follow-up time of 63 months. The results of the European Organisation for Research and Treatment of Cancer–Groupe d’Etude des Lymphomes de l’Adulte H9F trial are noteworthy with respect to the role of RT in favorable limited-stage HL. This trial randomly assigned 783 patients to address two important issues in the management of favorable early-stage HL. The dose of RT in patients who achieved complete remission (CR)/unconfirmed complete remission (CRu) after CT and the need for involved-field RT (IFRT) after CT were assessed in a randomized fashion. Patients who achieved CR/CRu after six cycles of epirubicin, vinblastine, bleomycin, and prednisone were randomly assigned to RT arms (36 v 20 Gy) or to a no RT arm. Seventy-seven percent of patients had CR/CRu after six cycles epirubicin, vinblastine, bleomycin, and prednisone, which was above the stopping rule value of 70%. The trial was closed as a result of significantly lower 5-year relapse-free survival rate in the no RT arm compared with the RT arms (70% v 86 v 89% for no RT, IFRT 36 Gy, and IFRT 20 Gy, respectively; P .001). Of note, the failure of the no RT arm might also be a result of the CT regimen used. This question is going to be answered in the H10 trial, which will also assess early CR after two cycles of ABVD with positron emission tomography scan. There was no difference in the OS, as expected with a short median follow-up time of 37 months. Nevertheless, it is important to note that these results are derived from a randomized trial, and thus, the level of evidence is higher than a retrospective study or an underpowered prospective trial. The results reported by Canellos et al could be considered important for hypothesis generating. Currently, CT combined with IFRT remains the preferred treatment option for patients with favorable limited-stage HL. The retrospective studies always have the possibility of selection bias, as stated by the authors. The low number of patients despite a long treatment period (1992 to 2008) from a single center suggests a difficult treatment decision-making process for recommending a nonstandard treatment option. Moreover, the study population includes stage IIB patients (15%), which is not consistent with the title of the article. Favorable limited-stage HL has a good prognosis; therefore, an optimal balance between efficacy and long-term toxicity is crucial. Improved imaging techniques and advances in RT technology have led to considerable progress in RT over the years. ABVD followed by IFRT based on modern RT principles has been shown to lower both acute and late treatment-related toxicities. In conclusion, we think that the results from this retrospective analysis should be interpreted with caution because such definitive conclusions based on retrospective analyses might be misleading for the oncology community, especially if they are published in prestigious journals like Journal of Clinical Oncology, which is read by all oncologists worldwide. The conclusion might be interpreted as six cycles of ABVD alone is the standard treatment option, and this treatment might be adopted by those who are not familiar with treatment of HL. Finally, we also believe that some patients with favorable early-stage disease might benefit from a response-adapted treatment strategy without RT; however, this strategy must be proven within the scope of prospective randomized clinical trials.