Laurenz Vormittag

UFT/leucovorin and mitomycin C as salvage treatment in patients with advanced colorectal cancer - a retrospective analysis.

Active anticancer drugs and/or combination regimens for the treatment of patients failing oxaliplatin, irinotecan and 5-fluorouracil are desperately needed. In this analysis we describe the safety and efficacy of the combination of mitomycin C, UFT and leucovorin in such an extensively pretreated patient population. Between January 2002 and June 2004, a total of 41 patients were treated with mitomycin C (8 mg/m2 on day 1) and UFT (350 mg/m2)+ leucovorin (90 mg) both divided into three daily doses from day 1 to day 14 every 4 weeks. All patients had failed prior first-line and second-line treatment with oxaliplatin, irinotecan and 5-fluorouracil. The aim of this retrospective analysis was to evaluate the efficacy and safety data of this potential salvage therapy regimen. Thirty-nine patients were evaluable for the response. The overall response rate (intent-to-treat) was 7.3% (95% confidence interval, 2.5–19.4%) and disease stabilization was achieved in 29.3%. Median time to progression was 2.5 months (range, 1.5–13.5) and median overall survival was 6 months (range, 1.5–26). Myelosuppression was the most frequent side effect. Grade 3 hematotoxicity, however, was observed in only three patients. The most common nonhematological toxicities consisted of mild and reversible nausea, emesis and diarrhea; again, severe symptoms were only occasionally seen. These data show that the combination of mitomycin C/UFT/leucovorin is safe and active in about one-third of patients in terms of abrogation of progression in extensively pretreated metastatic colorectal cancer.

7β-Hydroxycholesterol Induces Apoptosis and Regulates Cyclooxygenase 2 in Head and Neck Squamous Cell Carcinoma

OBJECTIVE To determine whether treatment with 7beta-hydroxycholesterol (7beta-HC) would trigger cell death in head and neck squamous cell carcinoma (HNSCC) cell lines in a dose-dependent fashion. DESIGN In vitro study. SUBJECTS The study included HNSCC cell lines SCC9, SCC25, CAL27, and FaDu. INTERVENTION We treated HNSCC cell lines with increasing doses of 7beta-HC. Proliferation assays were performed to assess cell viability after treatment. Western blots were carried out to evaluate cyclooxygenase (COX)-1 and -2 expression levels. RESULTS Using proliferation assays and immunocytochemical analysis, we detected significant growth inhibition via apoptosis in 4 different HNSCC cell lines after treatment with 7beta-HC (P < .001). The 50% inhibitory concentration levels were between 13.19 and 20.79 micromol/L after 72 hours. Western analysis indicated that COX-2, but not COX-1, levels were suppressed after treatment. CONCLUSIONS Treatment with 7beta-HC resulted in suppression of HNSCC growth in vitro. Our data warrant further investigations for the potential use of 7beta-HC as a cytotoxic agent in head and neck cancer.

Multimodal treatment of patients with minor salivary gland cancer in the case of recurrent disease

Our aim in this study was to identify prognostic factors and the optimal therapeutic management in patients with minor salivary gland carcinomas.

Comparison of 2.5 mg/kg and 5 mg/kg systemic bevacizumab in neovascular age-related macular degeneration: twenty-four week results of an uncontrolled, prospective cohort study.

Background: To compare safety, visual acuity (VA), and anatomic outcomes of 2.5 mg/kg and 5 mg/kg intravenous bevacizumab in patients with neovascular age-related macular degeneration. Methods: In an institutional cohort study, 16 patients (2 cohorts, 27 eyes) with neovascular age-related macular degeneration were treated with 5 mg/kg intravenous bevacizumab and 2.5 mg/kg, respectively. All patients received 3 initial intravenous infusions at 2-week intervals. The main outcome measures were VA, optical coherence tomography, and fluorescein angiography. Results: No serious systemic or ocular adverse events were identified. By Day 7, mean VA increased from 56 letters (20/80+1) at baseline to 60 letters (20/63) in the 5 mg/kg group and mean central retinal thickness decreased by 83 &mgr;m. In the 2.5 mg/kg group, mean VA increased from 55 letters (20/80) to 66 letters (20/50+1) and mean central retinal thickness decreased by 93 &mgr;m. By Month 3, VA improved by 10 letters compared to baseline in the 5 mg/kg group and by 9 letters in the 2.5 mg/kg group. Central retinal thickness was reduced by 128 &mgr;m in the 5 mg/kg group and by 127 &mgr;m in the 2.5 mg/kg group. These benefits were sustained through 6 months. No statistically significant difference was found between both treatment groups regarding safety, VA, and anatomic outcomes. Conclusion: Similar VA, optical coherence tomography, and angiographic improvements were observed in both treatment groups up to 6 months. Further follow-up is required to evaluate the long-term durability and safety of both treatment regimens.

Limited value of CA 19-9 in predicting early treatment failure in patients with advanced pancreatic cancer.

Objective: The role of CA 19-9 in monitoring treatment response in advanced pancreatic cancer remains uncertain. We assessed its value in predicting early failure of first-line chemotherapy. Methods: Data of 84 patients with advanced pancreatic cancer who had received first-line chemotherapy were analyzed with regard to changes in CA 19-9 during the first 2 months of treatment. Results: Median time to progression and overall survival in patients with a transient increase in CA 19-9 during month 1 (n = 15; 5.5 and 13 months) and in those with no increase during the 2 months (n = 52; 6.5 and 12 months) were comparable and slightly above the median values of the entire study population. The hazard ratios for disease progression for a 20% increase in CA 19-9 during the first and second month of therapy were 1.065 and 1.339 in the univariate- and 1.092 and 1.298 in the multiple Cox regression model, respectively. CA 19-9 did not influence survival. Conclusion: Our results suggest that early CA 19-9 measurements are weakly associated with disease progression rather than survival in patients with advanced pancreatic cancer receiving palliative chemotherapy. In view of a possible tumor marker flare, values after the first month of therapy must be interpreted with caution.

The effect of nimesulide, a selective cyclooxygenase-2 inhibitor, on Ets-1 and Ets-2 expression in head and neck cancer cell lines.

The protooncogenes Ets‐1 and Ets‐2 are involved in carcinogenesis of different tumors. Nimesulide, a selective cyclooxygenase‐2 (COX‐2) inhibitor, has antiproliferative effects on tumor cells. The question arises whether nimesulide influences Ets‐1 and Ets‐2 synthesis in head and neck tumors.

Unilateral face swelling as first manifestation of metastatic pancreatic cancer: case report and review of the literature.

ZusammenfassungHINTERGRUND: Metastatische Absiedlungen in den Kiefer-, Gesichtsbereich sind bei Patienten mit Pankreaskarzinom ungewöhlich und bislang erst in fünf Fällen beschrieben worden. FALLBERICHT: Ein 54-jähriger männlicher Patient suchte das Krankenhaus wegen einer Schwellung im Bereich des Unterkiefers auf. Histologisch bestand ein Adenokarzinom. Eine Computertomographie führte schließlich zur Diagnose eines Pankreaskarzinoms. Eine Radiochemotherapie wurde eingeleitet, jedoch frühzeitig aufgrund von intraoralen Blutungen im Bereich der Metastase wieder abgebrochen. In der Folge erhielt der Patient palliative Chemotherapie. Das Primum konnte stabilisiert werden, wohingegen die Raumforderung im Bereich der Mandibula weiter an Größe zunahm. Trotz maximaler Supportivtherapie verstarb der Patient im Januar 2007. SCHLUSSFOLGERUNG: Bei einer für Metastasen ungewöhnlichen Lokalisation wie der Mandibula sollte nicht nur Frage eines potentiell kurativen Therapieansatzes, sondern auch die möglicherweise geringere Sensitivität gegenüber konservativer Therapie und die Lebensqualität des Patienten in die Entscheidung, ob eine Metastasenresektion durchgeführt wird, miteinfließen.SummaryOBJECTIVE: Metastasis to the jaw is a rare finding in pancreatic cancer; only five cases of tumor spread to the oral region have been described. CASE REPORT: We report on a previously healthy 54-year-old man who attended the hospital in 2006 because of a mandibular mass. Histology was positive for adenocarcinoma and computed tomography led to the diagnosis of pancreatic cancer. Chemoradiotherapy was started but had to be stopped early because of intraoral bleeding from the metastasis. The patient subsequently received palliative chemotherapy. The primary cancer was stabilized but the mandibular mass progressed despite cytostatic therapy. Despite best supportive measures the patient died nine months after presentation. CONCLUSION: In making the decision on whether metastasectomy should be performed in an uncommon site of metastatic spread such as the mandibula, both the possibility of cure and also the potentially decreased response to conservative therapy and the patients decreased quality of life have to be considered.