Jan Pintoffl

Bendamustine hydrochloride in patients with refractory soft tissue sarcoma: a noncomparative multicenter phase 2 study of the German sarcoma group (AIO-001).

For patients with advanced soft tissue sarcoma (STS), no standard treatment is established after previous chemotherapy with anthracyclines and ifosfamide. Bendamustine hydrochloride is a bifunctional alkylating agent that is not cross‐resistant to other DNA‐interacting substances including anthracyclines and oxazaphosphorines. It has shown single‐agent activity in refractory lymphoma, myeloma, and some solid tumors. A phase 2 study was initiated to evaluate the efficacy of bendamustine in previously treated patients.

Evaluation of Response in Malignant Tumors Treated With the Multitargeted Tyrosine Kinase Inhibitor Sorafenib: A Multitechnique Imaging Assessment

OBJECTIVE The purpose of this article is to illustrate the characteristic changes induced in different tumor types by the multitargeted tyrosine kinase inhibitor sorafenib. CONCLUSION Sorafenib reduces tumor perfusion and thereby induces necrosis and often hemorrhage. Malignant tumors treated with sorafenib undergo both morphologic and functional changes; however, the morphologic changes are less frequent and inadequate for early evaluation of response. Therefore, imaging tools accurately assessing hemorrhage and decrease in tumor perfusion with subsequent necrosis should be the mainstay in monitoring targeted therapy agents.

Mitomycin C plus Infusional 5-Fluorouracil in Platinum-Refractory Gastric Adenocarcinoma: An Extended Multicenter Phase II Study

To assess the toxicity and activity of bolus mitomycin C (MMC) in combination with a 24-hour continuous infusion of 5-fluorouracil (5-FU) in gastric cancer patients who had received at least one prior chemotherapy regimen. Patients and Methods: Patients were treated with MMC (10 mg/m2) on days 1 and 22, 5-FU (2.6 g/m2) as a 24-hour infusion, and folinic acid 500 mg/m2 weekly for 6 weeks. Results: Thirty-four patients with gastric cancer, 16 after failure of first-line chemotherapy and 18 after failure of at least two prior chemotherapies, were included. In the intent-to-treat analysis, 9 (26.5%) of the 34 patients had a partial response and 10 (29.4%) a disease stabilization (disease control rate 56%). The median time to progression was 3.3 months (CI95: 2.8-3.7), and the median overall survival was 7.2 months (CI95: 5.9-8.4). Grade III/IV thrombocytopenia occurred in 14.7% of patients (n = 5), while the most frequent nonhematological grade III/IV toxicities were mucositis and diarrhea, each affecting 9% of patients. Conclusions: As the tested regimen was generally safe and well tolerated by the patients, MMC plus infusional 5-FU/folinic acid may be a potential second-line regimen for patients with advanced gastric cancer.

Gefitinib in combination with oxaliplatin and 5-fluorouracil in irinotecan-refractory patients with colorectal cancer: a phase I study of the Arbeits gemeinschaft Internistische Onkologie (AIO).

Background: The aim of the study was to establish the recommended dose and to evaluate the safety of gefitinib plus FUFOX regimen in irinotecan-refractory colorectal carcinoma (CRC). Patients and Methods: Patients with advanced CRC progressing on fluoropyrimidine/irinotecan-based chemotherapy and with an ECOG performance level 0–2 were enrolled. Four dose levels with sequential dose escalation of oral gefitinib and FUFOX were tested. Each cycle consisted of 5 weeks with gefitinib given daily to weekly FUFOX ×4 to be repeated at day 36. Results: Eighteen patients were enrolled. No dose-limiting toxicity (DLT) was observed at the dose levels L1–L3. At L4 diarrhea was the major DLT requiring treatment interruption in 3 patients. Other grade 3/4 toxicities were observed with skin rash, paresthesia, anemia, and nausea/vomiting (n = 1 each). Grade 1/2 toxicities consisted of diarrhea (n = 9), mucositis (8), skin rash (10), paresthesia (10), nausea (7) as well as leukopenia (2) and fever (1). Clinical benefit was seen in 11 of 16 evaluable patients (69%): 4 patients showed partial response (25%), 7 stable disease (44%). Median time to progression was 219 days (range 50–387 days). Conclusion: Gefitinib at a dose of 250 mg daily in combination with weekly 5-fluorouracil at 2,000 mg/m2 or gefitinib at a dose of 500 mg daily with 5-fluorouracil at 1,600 mg/m2 plus oxaliplatin has an acceptable safety profile.

Marginal Zone B-Cell Non-Hodgkin's Lymphoma of Mucosa-Associated Lymphoid Tissue Type: Imaging Findings

OBJECTIVE The aim of this essay is to describe the imaging features of marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type throughout various organs. CONCLUSION Awareness of the expected locations of MALT lymphoma combined with knowledge of the incidence and imaging findings leads to accurate diagnosis of lesions suspicious for this disorder and helps to differentiate this disease from other abnormalities.

Perfusion and Flow Extraction Product as Potential Discriminators in Untreated Follicular and Diffuse Large B Cell Lymphomas Using Volume Perfusion CT With Attempt at Histopathologic Explanation

OBJECTIVE The purpose of this article is to measure perfusion parameters, including transit constant (K(trans)), in untreated follicular and diffuse large B cell lymphoma using volume perfusion CT, to establish their discriminating role and to search for a possible histopathologic background. SUBJECTS AND METHODS Between January 2010 and June 2011, 46 consecutive patients with untreated histologically confirmed follicular lymphoma (n = 16) or diffuse large B cell lymphoma (n = 30) were enrolled. A 40-second volume perfusion CT of the tumor bulk using 6.9-cm z-axis coverage and a total of 26 volume measurements was performed. Blood flow (BF), blood volume (BV), and K(trans) were determined. Tumor size was recorded as the product of long- and short-axis diameters. In 13 of 46 patients, pathologic specimens of an appropriate size were available for assessment of microvessel density (MVD) and microvascular luminal diameter for comparison with volume perfusion CT measurements. RESULTS Mean BF, BV, and K(trans) values were significantly higher in follicular lymphoma than in diffuse large B cell lymphoma, even after controlling for patient age and tumor size (p < 0.05, respectively). Although MVD was slightly, but not significantly, higher in follicular lymphoma versus diffuse large B cell lymphoma (p > 0.05), microvascular luminal diameter was significantly larger in follicular lymphoma than in diffuse large B cell lymphoma (p < 0.05). We defined cutoff values for BF, BV, and K(trans). If the cutoff points are met for all three parameters, the overall accuracy for correctly identifying diffuse large B cell lymphoma and follicular lymphoma was 90.5% and 87.5%, respectively. CONCLUSION Volume perfusion CT allows assessment of differences in vascularity of follicular and diffuse large B cell lymphomas, reflecting vascular luminal variability and histopathologic anatomy.

Long-term disease stabilization during second-line gemcitabine in a refractory metastatic haemangioendothelioma.

Departments of Medical Oncology, Hematology, Immunology, Rheumatology, Pulmology, Medical Center II, Diagnostic Radiology, Pathology and Interdisciplinary Sarcoma Center, South West German Cancer Center, Eberhard-Karls-University, Tuebingen, Germany Correspondence to Professor Dr Jörg Thomas Hartmann, MD, Departments of Medical Oncology, Hematology, Immunology, Rheumatology, Pneumology, South West German Comprehensive Cancer Center, Eberhard-Karls-University, Tuebingen, Tuebingen 72076, Germany Tel: + 49 7071 29 82127; fax: + 49 7071 29 4399; e-mail: joerg.hartmann@med.uni-tuebingen.de

Diffuse alveolar hemorrhage in patients with hematological malignancies: HRCT patterns of pulmonary involvement and disease course

OBJECTIVE To analyze high-resolution computed tomography (HRCT) patterns of lung involvement and disease course in patients with hematological malignancies experiencing diffuse alveolar hemorrhage (DAH) after chemotherapy ± allogeneic stem cell transplantation (allo-SCT). MATERIALS AND METHODS Sixteen patients experiencing DAH after chemotherapy ± allo-SCT were enrolled. A total of 74 computed tomography (CT) scans obtained before, during, and after onset of DAH were evaluated retrospectively. RESULTS CT features of DAH are each, by oneself, nonspecific. However, conjoint bilateral, diffuse, and dependent ground glass opacity ± crazy paving, accompanied by airspace bronchograms, should suggest this complication. The HRCT course comprises a wide range of trends that are not predictive for patients outcome, but progression of parenchymal consolidations at follow up was more often detrimental.

Role of dynamic contrast-enhanced sonography for characterization and monitoring of extramedullary myeloma: comparison with serologic data.

To measure blood perfusion in extramedullary myeloma by contrast‐enhanced sonography, correlate it with specific hematologic parameters, and determine their utility for local and systemic response monitoring.

Abstract 2496: Epothilones synergistically induce CRC cell death in combination with standard chemotherapy in part through a p53-dependent pathway

Epothilones are a novel class of microtubule stabilizing agents with known antitumor activity. However, clinical response rates to epothilones vary widely, and the underlying molecular mechanisms that predict response to therapy remain to be clarified. Loss of p53 tumor suppressor pathway function is a common event in many cancers, including colorectal cancer (CRC). However, it is yet unknown how p53 status affects the response to epothilones in CRC. To explore the role of the p53 pathway in epothilone antitumor activity, we quantified the antitumor efficacy of Patupilone (Pp) and Ixabepilone (Ix) in combination with standard CRC chemotherapy agents in isogenic HCT116 p53+/+ and p53-/- as well as in isogenic RKO and SW48 p53+/+ and -/- cell lines. Cells were treated with oxaliplatin (Ox), 5-flourouracil (5FU), irinotecan (Ir) as well as Pp and Ix in different doses and combinations, and cell cycle perturbations and apoptosis induction were determined. We found that all the tested agents induced cell death in a dose- and p53 status-dependent manner. Both epothilones displayed enhanced antitumor activity in p53+/+ cells compared to p53-/- cells, suggesting a p53 dependent mechanism; however, Pp induced apoptosis more efficiently than Ix as single agent (IC50s for Pp in p53+/+ cells 15nm and in p53-/- cells 50nm; IC50s for Ix 50nm and >100nm respectively). Intriguingly, Pb and Ix induced a G2/M checkpoint arrest in p53+/+, but not p53-/- cells. Addition of Ix or Pb to either Ox, 5FU or Ir dramatically enhanced apoptosis in p53+/+ and -/- cells at doses that normally did not demonstrate any antitumor activity when administered as single agents. In p53 +/+ cells oxaliplatin alone induced 50% apoptosis at a concentration of 50 µM; Pp alone at 2 nM induced 25% apoptosis. However when IC50 of Ox was combined with 2nM Pp, we found a dramatic apoptosis-induction of >95%. This synergistic effect was less pronounced in p53-/- cells, however in p53-/- cells, addition of epothilones to standard chemotherapy also increased response rates efficiently compared to standard chemotherapy alone with 50µM Ox alone inducing 80% apoptosis in p53-/- cells. Similar intriguing results were seen for combinations of 5FU or Ir with Pb, as well as for combinations of standard chemotherapy with Ix. Thus, epothilones dramatically potentiate the efficacy of standard CRC chemotherapy (Ox, 5FU, Ir), and apoptosis induction is largely dependent on p53 status. These findings suggest that epothilones in combination with current standard chemotherapeutics in CRC may be clinically useful, and that evaluation of p53 status should be taken into consideration during the design of future clinical trials using these classes of agents. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2496.