http://www.jhoonline.org The latest research articles published by Journal of Hematology & Oncology 2010-03-11T00:00:00Z This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ Background: Canfosfamide is a novel glutathione analog activated by glutathione S-transferase P1-1. This study evaluated the safety and efficacy of canfosfamide in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum resistant ovarian cancer. Patients with platinum resistant ovarian carcinoma and measurable disease received canfosfamide at 960 mg/m2 in combination with PLD at 50 mg/m2, intravenously Day 1 in every 28 day cycles until tumor progression or unacceptable toxicities. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS). Results: Canfosfamide plus PLD combination therapy was administered at 960/50 mg/m2. Thirty-nine patients received a median number of 4 cycles (range 1.0-18.0). The ORR was 27.8% (95% CI, 14.2-45.2) with a disease stabilization rate of 80.6% (95% CI, 64.0-91.8) in the evaluable population. The CA 125 marker responses correlated with the radiological findings of complete response or partial response. The median PFS was 6.0 months (95% CI, 4.2-7.9) and median survival was 17.8 months. The combination was well tolerated. Myelosuppression was managed with dose reductions and growth factor support. Grade 3 febrile neutropenia was observed in 2 patients (5.1%). Non-hematologic adverse events occurred at the expected frequency and grade for each drug alone, with no unexpected or cumulative toxicities. Conclusions: Canfosfamide in combination with PLD is well tolerated and active in platinum and paclitaxel refractory or resistant ovarian cancer. A randomized phase 3 study was conducted based on this supportive phase 2 study.Trial Registration: This study was registered at www.clinicaltrials.gov: NCT00052065. http://www.jhoonline.org/content/3/1/9 John Kavanagh Charles Levenback Pedro Ramirez Judith Wolf Carla Moore Marsha Jones Lisa Meng Gail Brown Robert Bast Journal of Hematology & Oncology 2010, 3:9 2010-03-11T00:00:00Z doi:10.1186/1756-8722-3-9 Journal of Hematology & Oncology 1756-8722 3 9 2010-03-11T00:00:00Z PDF The Ras-dependent Raf/MEK/ERK1/2 mitogen-activated protein (MAP) kinase signaling pathway is a major regulator of cell proliferation and survival. Not surprisingly, hyperactivation of this pathway is frequently observed in human malignancies as a result of aberrant activation of receptor tyrosine kinases or gain-of-function mutations in RAS or RAF genes. Components of the ERK1/2 pathway are therefore viewed as attractive candidates for the development of targeted therapies of cancer. In this article, we briefly review the basic research that has laid the groundwork for the clinical development of small molecules inhibitors of the ERK1/2 pathway. We then present the current state of clinical evaluation of MEK1/2 inhibitors in cancer and discuss challenges ahead. http://www.jhoonline.org/content/3/1/8 Christophe Fremin Sylvain Meloche Journal of Hematology & Oncology 2010, 3:8 2010-02-11T00:00:00Z doi:10.1186/1756-8722-3-8 Journal of Hematology & Oncology 1756-8722 3 8 2010-02-11T00:00:00Z XML Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer. http://www.jhoonline.org/content/3/1/7 Bei Liu John Nash Carolyn Runowicz Helen Swede Richard Stevens Zihai Li Journal of Hematology & Oncology 2010, 3:7 2010-02-10T00:00:00Z doi:10.1186/1756-8722-3-7 Journal of Hematology & Oncology 1756-8722 3 7 2010-02-10T00:00:00Z XML ObjectiveTo report serial 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) tumor response following CyberKnife radiosurgery for stage IA non-small cell lung cancer (NSCLC). Methods: Patients with biopsy-proven inoperable stage IA NSCLC were enrolled into this IRB-approved study. Targeting was based on 3-5 gold fiducial markers implanted in or near tumors. Gross tumor volumes (GTVs) were contoured using lung windows; margins were expanded by 5 mm to establish the planning treatment volumes (PTVs). Doses ranged from 42-60 Gy in 3 equal fractions. 18F-FDG PET/CT was performed prior to and at 3-6-month, 9-15 months and 18-24 months following treatment. The tumor maximum standardized uptake value (SUVmax) was recorded for each time point. Results: Twenty patients with an average maximum tumor diameter of 2.2 cm were treated over a 3-year period. A mean dose of 51 Gy was delivered to the PTV in 3 to 11 days (mean, 7 days). The 30-Gy isodose contour extended an average of 2 cm from the GTV. At a median follow-up of 43 months, the 2-year Kaplan-Meier overall survival estimate was 90% and the local control estimate was 95%. Mean tumor SUVmax before treatment was 6.2 (range, 2.0 to 10.7). During early follow-up the mean tumor SUVmax remained at 2.3 (range, 1.0 to 5.7), despite transient elevations in individual tumor SUVmax levels attributed to peritumoral radiation-induced pneumonitis visible on CT imaging. At 18-24 months the mean tumor SUVmax for controlled tumors was 2.0, witha narrow range of values (range, 1.5 to 2.8). A single local failure was confirmed at 24 months in a patient with an elevated tumor SUVmax of 8.4. Conclusion: Local control and survival following CyberKnife radiosurgery for stage IA NSCLC is exceptional. Early transient increases in tumor SUVmax are likely related to radiation-induced pneumonitis. Tumor SUVmaxvalues return to background levels at 18-24 months, enhancing 18F-FDG PET/CT detection of local failure. The value of 18F-FDG PET/CT imaging for surveillance following lung SBRT deserves further study. http://www.jhoonline.org/content/3/1/6 Saloomeh Vahdat Eric Oermann Sean Collins Xia Yu Malak Abedalthagafi Pedro DeBrito Simeng Suy Shadi Yousefi Constanza Gutierrez Thomas Chang Filip Banovac Eric Anderson Giuseppe Esposito Brian Collins Journal of Hematology & Oncology 2010, 3:6 2010-02-04T00:00:00Z doi:10.1186/1756-8722-3-6 Journal of Hematology & Oncology 1756-8722 3 6 2010-02-04T00:00:00Z XML Histone deacetylases (HDACs) can regulate expression of tumor suppressor genes and activities of transcriptional factors involved in both cancer initiation and progression through alteration of either DNA or the structural components of chromatin. Recently, the role of gene repression through modulation such as acetylation in cancer patients has been clinically validated with several inhibitors of HDACs. One of the HDAC inhibitors, vorinostat, has been approved by FDA for treating cutaneous T-cell lymphoma (CTCL) for patients with progressive, persistent, or recurrent disease on or following two systemic therapies. Other inhibitors, for example, FK228, PXD101, PCI-24781, ITF2357, MGCD0103, MS-275, valproic acid and LBH589 have also demonstrated therapeutic potential as monotherapy or combination with other anti-tumor drugs in CTCL and other malignancies. At least 80 clinical trials are underway, testing more than eleven different HDAC inhibitory agents including both hematological and solid malignancies. This review focuses on recent development in clinical trials testing HDAC inhibitors as anti-tumor agents. http://www.jhoonline.org/content/3/1/5 Jiahuai Tan Shundong Cang Yuehua Ma Richard Petrillo Delong Liu Journal of Hematology & Oncology 2010, 3:5 2010-02-04T00:00:00Z doi:10.1186/1756-8722-3-5 Journal of Hematology & Oncology 1756-8722 3 5 2010-02-04T00:00:00Z XML No standard has been established for salvage therapy in gemcitabine refractory advanced urothelial cancer. We report the complete response to FOLFOX4 therapy of a metastatic urothelial cancer patient, for whom adjuvant gemcitabine plus cisplatin combination chemotherapy had failed. A 54-year-old male patient with urothelial cancer (transitional cell carcinoma) in the right kidney underwent three rounds of adjuvant gemcitabine-cisplatin chemotherapy after extensive radical nephrectomy. However, he had new liver, lung metastases and synchronous two separate primary colon cancer. The lung metastasis lesion was confirmed as a metastatic urothelial cancer via percutaneous transthoracic needle biopsy (PTNB). Liver and lung metastasis lesions disappeared after the 4th cycle of FOLFOX4 chemotherapy. In addition, colon cancer also disappeared after the 8th cycle of FOLFOX4 chemotherapy. The patient was still showing a complete response after 4 months. Clinical trials using the FOLFOX regimen as salvage therapy for gemcitabine-refractory advanced urothelial cancer are warranted. http://www.jhoonline.org/content/3/1/4 Yu Ri Seo Se Hyung Kim Hyun Jung Kim Chan Kyu Kim Sung Kyu Park Eun Suk Koh Dae Sik Hong Journal of Hematology & Oncology 2010, 3:4 2010-01-20T00:00:00Z doi:10.1186/1756-8722-3-4 Journal of Hematology & Oncology 1756-8722 3 4 2010-01-20T00:00:00Z XML Cancer patients are at increased risk of venous thromboembolism due to a range of factors directly related to their disease and its treatment. Given the high incidence of post-surgical venous thromboembolism in cancer patients and the poor outcomes associated with its development, thromboprophylaxis is warranted. A number of evidence-based guidelines delineate anticoagulation regimens for venous thromboembolism treatment, primary and secondary prophylaxis, and long-term anticoagulation in cancer patients. However, many give equal weight to several different drugs and do not make specific recommendations regarding duration of therapy. In terms of their efficacy and safety profiles, practicality of use, and cost-effectiveness the low-molecular-weight heparins are at least comparable to, and offer several advantages over, other available antithrombotics in cancer patients. In addition, data are emerging that the antithrombotics, and particularly low-molecular-weight heparins, may exert an antitumor effect which could contribute to improved survival in cancer patients when given for long-term prophylaxis. Such findings reinforce the importance of thromboprophylaxis with low-molecular-weight heparin in cancer patients. http://www.jhoonline.org/content/3/1/3 Francisco Robert Journal of Hematology & Oncology 2010, 3:3 2010-01-14T00:00:00Z doi:10.1186/1756-8722-3-3 Journal of Hematology & Oncology 1756-8722 3 3 2010-01-14T00:00:00Z XML Leser-Trélat syndrome is characterized by the eruptive appearance of multiple seborrheic keratoses in association with underlying malignant disease. Usually, the sign of Leser-Trélat is associated with adenocarcinoma, most frequently of the colon, breast, or stomach, but also of the lung, kidney, liver, and pancreas. Herein, we present a case that we believe is the first report of the sign of Leser-Trélat in association with occult gastric adenocarcinoma and the anamnestic oncologic history of five other multiple primitive cancers. Epidermal growth factor receptor (EGFR) immunohistochemical expression analysis of multiple seborrheic keratoses revealed an intense membranous staining in the basal keratinocytes and in all the upper epidermal layers. Patients with the sign of Leser-Trélat should undergo a diagnostic screening programme for malignant disease along with patients with known Leser-Trélat syndrome who present with a recent acute and florid eruption of their seborrheic keratoses. We propose the importance of combining the molecular features of multiple seborrheic keratoses with EGFR immunohistochemistry analyses to determine the likelihood of Leser-Trélat syndrome and the consequent high risk of underlying multiple visceral malignancies. http://www.jhoonline.org/content/3/1/2 Giovanni Ponti Gabriele Luppi Lorena Losi Alberto Giannetti Stefania Seidenari Journal of Hematology & Oncology 2010, 3:2 2010-01-11T00:00:00Z doi:10.1186/1756-8722-3-2 Journal of Hematology & Oncology 1756-8722 3 2 2010-01-11T00:00:00Z XML Background: Thalidomide based regimen is an effective and well tolerated therapy in multiple myeloma (MM) patients, however, there were a small number of studies written about the results of thalidomide therapy in non-transplant MM patients. We therefore conducted a retrospective study of 42 consecutive patients with newly diagnosed and relapsed/refractory MM treated with thalidomide- based induction regimens followed by thalidomide maintenance therapy. Results: Induction regimens with thalidomide and dexamethasone, and the oral combination of melphalan, prednisolone and thalidomide were administrated in 22 and 16 patients, respectively. The remaining 4 patients received other thalidomide- containing regimens. Twenty-nine patients received thalidomide as a salvage regimen. Twenty-three out of 26 patients achieving complete remission (CR) and very good partial remission (VGPR) received thalidomide maintenance. Of the 41 evaluable patients, median time of treatment was 21 months (3- 45 months), ORR was 92.7% with a 63.4% CR/VGPR. With a median follow up of 23 months, 3-year- PFS and 3-year-OS were 58.6 and 72.6%, respectively. Median time to progression was 42 months. While 3-year-PFS and 3-year-OS in non-transplant patients receiving thalidomide maintenance therapy were 67 and 80%, respectively. Conclusions: Prolonged thalidomide therapy enhanced survival rate and less frequently developed serious toxicity in non-transplant multiple myeloma patients. http://www.jhoonline.org/content/3/1/1 Pimjai Niparuck Ladda Sorakhunpipitkul Vichai Atichartakarn Suporn Chuncharunee Artit Ungkanont Pantep Aungchaisuksiri Teeraya Puavilai Saengsuree Jootar Journal of Hematology & Oncology 2010, 3:1 2010-01-05T00:00:00Z doi:10.1186/1756-8722-3-1 Journal of Hematology & Oncology 1756-8722 3 1 2010-01-05T00:00:00Z XML We have described a severe combined immunodeficiency (SCID) mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL) and 66 acute myeloid leukemia (AML)) in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8%) displayed an aggressive growth pattern, 14 (10.5%) displayed an indolent growth pattern and 74 (55.6%) did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course. http://www.jhoonline.org/content/2/1/51 Ying Yan Eric Wieman Xiuqin Guan Ann Jakubowski Peter Steinherz Richard O'Reilly Journal of Hematology & Oncology 2009, 2:51 2009-12-29T00:00:00Z doi:10.1186/1756-8722-2-51 Journal of Hematology & Oncology 1756-8722 2 51 2009-12-29T00:00:00Z XML