Basak Oyan

HER2-targeted therapy in breast cancer: A systematic review of neoadjuvant trials

Targeting human epidermal growth factor receptor 2 (HER2) during or in sequence with chemotherapy improves overall survival in metastatic and early HER2-overexpressing breast cancer. In this paper we systematically review neoadjuvant clinical trial data in HER2-positive breast cancer and discuss key unanswered clinical questions. All trials of HER2-targeted neoadjuvant therapy were identified through non-date-limited searches of PubMED® and Biosis® and congress abstract book searches from 2000-2011. Eligible trials were prospective, had at least 10 patients and a clear definition of pathological complete response (pCR) rate. A total of 50 trials fulfilled the eligibility criteria; 41 single-arm phase II studies were identified, 37 with trastuzumab and 4 with lapatinib, with significant variability in baseline tumour characteristics and pCR rates (range 12-66.7%). Of 9 randomised phase II/III trials, 4 assessed the addition of trastuzumab to chemotherapy and a further 5 randomised trials assessed different HER2-targeting approaches. Four of these studies assessed dual HER2-targeting approaches, which universally increased pCR at the expense of increased non-cardiac toxicity when lapatinib, but not pertuzumab, was added to trastuzumab. Significant advances have been made in HER2 targeting, resulting in a marked increase in the number of breast cancer patients experiencing tumour pCR. Mature data from randomised neoadjuvant and adjuvant studies are awaited for survival outcomes with combination targeted approaches. Unanswered questions centre on the individualisation of therapy and include; which, if any, chemotherapy backbone should be used, and which patients need dual HER2 blockade?

Why do targeted agents not work in the adjuvant setting in colon cancer

The standard adjuvant treatment of stage III and high-risk stage II colon cancer is to administer 6 months of oxaliplatin- and fluorouracil-containing chemotherapy. However, nearly a third of stage III patients still recur. The positive results of cetuximab and bevacizumab added to chemotherapy in patients with metastatic colorectal cancer formed the basis to explore the role of these agents in the adjuvant setting. However, two adjuvant trials with bevacizumab and one adjuvant trial with cetuximab have failed to show any benefit of adding these agents to standard chemotherapy. Although reasons for the negative results remain unknown, the divergent effects of bevacizumab and cetuximab in early- versus advanced stage colon-cancer reinforce the notion that adjuvant and metastatic settings represent distinct diseases that require different treatments. This article summarizes the results of the adjuvant bevacizumab and cetuximab trials and discusses the possible explanations why molecularly targeted agents had no impact on improving the outcomes of adjuvant treatment of colon cancer.

Comparison of Metabolic and Anatomic Response to Chemotherapy Based on PERCIST and RECIST in Patients with Advanced Stage Non-small Cell Lung Cancer

BACKGROUND The aim of this study was to explore the prognostic role of metabolic response to chemotherapy, determined by FDG-PET, in patients with metastatic non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS Thirty patients with metastatic NSCLC were analyzed for prognostic factors related to overall survival (OS) and progression free survival (PFS). Disease evaluation was conducted with FDG-PET/CT and contrast-enhanced CT prior to and at the end of first-line chemotherapy. Response evaluation of 19 of 30 patients was also performed after 2-3 cycles of chemotherapy. Morphological and metabolic responses were assessed according to RECIST and PERCIST, respectively. RESULTS The median OS and PFS were 11 months and 6.2 months, respectively. At the end of first-line chemotherapy, 10 patients achieved metabolic and anatomic responses. Of the 19 patients who had an interim response analysis after 2-3 cycles of chemotherapy, 3 achieved an anatomic response, while 9 achieved a metabolic response. In univariate analyses, favorable prognostic factors for OS were number of cycles of first-line chemotherapy, and achieving a response to chemotherapy at completion of therapy according to the PERCIST and RECIST. The OS of patients with a metabolic response after 2-3 cycles of chemotherapy was also significantly extended. Anatomic response at interim analysis did not predict OS, probably due to few patients with anatomic response. In multivariate analyses, metabolic response after completion of therapy was an independent prognostic factor for OS. CONCLUSIONS Metabolic response is at least as effective as anatomic response in predicting survival. Metabolic response may be an earlier predictive factor for treatment response and OS in NSCLC patients.

Alprazolam Significantly Improves the Efficacy of Granisetron in the Prophylaxis of Emesis Secondary to Moderately Emetogenic Chemotherapy in Patients with Breast Cancer

Background: Alprazolam, a newer benzodiazepine, may be useful in the control of nausea and vomiting in breast cancer patients. Methods: Nineteen operable breast cancer patients were included in this randomized prospective crossover open-label trial. Patients received either granisetron (G) alone, or in combination with alprazolam (A). Group A patients received G+A first and then crossed over to G-alone after the 2nd or 3rd cycle. Group B patients received the reverse order. Eighty-four cycles were evaluated. Results: In group A, complete remission (CR) plus major response (MR) was higher (93.9%) with G+A than with G-alone (83.3%; p = 0.0001) in the first 24-hour period. In group B, CR plus MR was higher in G+A cycles (100%) than in G-alone cycles (85.7%; p = 0.035) in the 24-hour period and in the 25- to 129-hour period (92 vs. 90.5%, respectively; p = 0.022). Conclusion: Alprazolam increases the efficacy of granisetron in patients with breast cancer treated with an anthracycline-containing regimen.

Bone health in breast cancer patients: A comprehensive statement by CECOG/SAKK Intergroup

Bone is the most common site of distant metastases in breast cancer that can cause severe and debilitating skeletal related events (SRE) including hypercalcemia of malignancy, pathologic fracture, spinal cord compression and the need for palliative radiation therapy or surgery to the bone. SRE are associated with substantial pain and morbidity leading to frequent hospitalization, impaired quality of life and poor prognosis. The past 25 years of research on the pathophysiology of bone metastases led to the development of highly effective treatment options to delay or prevent osseous metastases and SRE. Management of bone metastases has become an integral part of cancer treatment requiring expertise of multidisciplinary teams of medical and radiation oncologists, surgeons and radiologists in order to find an optimal treatment for each individual patient. A group of international breast cancer experts attended a Skeletal Care Academy Meeting in November 2012 in Istanbul and discussed current preventive measures and treatment options of SRE, which are summarized in this evidence-based consensus for qualified decision- making in clinical practice.

Voltage-gated sodium channel blockers can augment the efficacy of chemotherapeutics by their inhibitory effect on epithelial-mesenchymal transition

Epithelial-mesenchymal transition (EMT) is a process during which cancer cells become more invasive and chemo resistant. EMT may also be associated with tumor dormancy which prevents the cure of cancer with adjuvant treatment. Chemo resistance and dormancy may also decrease response to cytotoxic agents during treatment of metastatic disease. Voltage gated sodium channels (VGSCs) are overexpressed in many cancer types, particularly in those with more aggressive and metastatic potential. VGSCs are thought to be associated with increased invasive and migratory capacity of cancer cells. Inhibition of VGSCs may inhibit EMT and angiogenesis through interaction with intracellular calcium activity and endothelial cells respectively. Blockage of these channels combined with other anticancer therapies may be effective in both adjuvant and palliative setting. Colonization at secondary site may be decelerated by VGSCs inhibition through impeding angiogenesis. This may lead to a temporary palliation of symptoms related to tumor burden in patients with metastatic disease.

Development of acute pulmonary hypertension after bortezomib treatment in a patient with multiple myeloma: a case report and the review of the literature.

Bortezomib is widely used in treatment of multiple myeloma. In recent years, severe bortezomib-induced lung injury has been reported. The clinical course is generally characterized with fever and dyspnea, followed by respiratory failure with pulmonary infiltrates. Herein, we report a 57-year-old man with newly diagnosed multiple myeloma admitted with dyspnea, fever, and hypotension on the third day of the first dose of bortezomib therapy. He had bilateral jugular venous distention, crackles at the bases of the lungs and hepatomegaly. Transthoracic echocardiography revealed acute pulmonary hypertension (PH) with an estimated pressure of 70 mm Hg. The perfusion scintigraphy ruled out pulmonary embolism, and microbiological examination was negative. On his course, fever, dyspnea, hypoxia, and pulmonary vascular pressure subsided rapidly. The sudden onset of PH and its rapid decrement without any treatment suggests bortezomib as the underlying cause. Subsequently, the patient did not respond to vincristine-doxorubicin-dexamethasone regimen and thalidomide. Bortezomib treatment was repeated, and no pulmonary adverse reactions occurred. Follow-up echocardiographies revealed pulmonary arterial pressures to be maximally of 35 mm Hg. To our knowledge, this is the first case of acute PH after front-line bortezomib therapy. In this report, we review bortezomib-related pulmonary complications in the literature and possible underlying mechanisms.

Unicentric mixed variant Castleman disease associated with Hashimoto disease: the role of PET/CT in staging and evaluating response to the treatment.

Abstract Castleman disease (CD) is a rare atypical lymphoproliferative disease, pathologically classified as hyaline vascular, plasma cell type and mixed type variant. The underlying cause of CD is unknown, however several theories including autoimmunity have been proposed. We describe a patient diagnosed with unicentric mixed variant CD and Hashimoto thyroiditis, concurrently. She was staged with fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) and the disease was localized to the mediastinum. After 6 cycles of chemotherapy consisting of vincristine and prednisone, the mediastinal lymph nodes regressed, but did not disappear from the CT scan. However, FDG-PET/CT showed complete metabolic response. Although the role of FDG-PET/CT in staging and evaluation of treatment response is controversial, this case shows that PET/CT can be effective and even better for staging and response evaluation. This case is also unique as there no case of CD in association with Hashimoto thyroiditis has been reported previously. However, the possibility of a coincidental association must be raised, especially when the high prevalence of Hashimoto thyroiditis is considered.

Pituitary Metastasis of Colon Adenocarcinoma: A Rare Occurrence

Metastasis to the pituitary gland from solid tumors is quite rare [1, 2]. It is usually detected in the presence of widespread metastatic disease [1–4]. The most common primaries of metastatic pituitary carcinomas are breast and lung cancers [2, 3]. Pituitary metastases are usually asymptomatic and constitute a small fraction of pituitary masses [3, 4]. Symptoms of pituitary metastasis may vary from visual disturbance to endocrine dysfunction such as diabetes insipidus [2, 5] and are caused by mass effect and compression of surrounding structures [5, 6]. Brain metastasis, particularly to the pituitary gland, from colorectal cancer is infrequent [7, 9]. Herein, we report a case of colon carcinoma with metastasis to the pituitary gland which developed diabetes insipidus and central hypothyroidism during follow-up.

IIVP Salvage Regimen Induces High Response Rates in Patients With Relapsed Lymphoma Before Autologous Stem Cell Transplantation

Patients with relapsed lymphoma can be cured with high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). New therapeutic approaches with better cytoreductive capacity are needed for relapsed patients to keep their chance for cure with transplantation. We report 30 patients with relapsed lymphoma, median age 43 years, treated with IIVP salvage regimen consisting of ifosfamide, mesna, idarubicin, and etoposide for 2 or 3 cycles. Seventeen patients had non-Hodgkin lymphoma (NHL) and 13 patients had Hodgkin disease (HD). Fourteen (47%) patients were at their first relapse. Overall response rate was 86.6% (n = 26) with 19 patients (63.3%) achieving complete response. Overall response rate was 92% in patients with HD and 82% in NHL. The most frequent side effects observed were grade III–IV neutropenia (87%) and thrombocytopenia (73%). IIVP regimen is a highly effective salvage therapy for patients with relapsed HD or NHL who are candidates for autologous HSCT. Close follow up is necessary because of the high incidence of grade III–IV hematologic toxicity.