DocOx (AIO-PK0106): a phase II trial of docetaxel and oxaliplatin as a second line systemic therapy in patients with advanced pancreatic ductal adenocarcinoma.

BACKGROUND: The current study was conducted to examine the activity of a docetaxel/oxaliplatin (DocOx) combination as second line treatment for advanced pancreatic ductal adenocarcinoma (Trial registration: NCT00690300. Registered June 2, 2008) METHODS: DocOx is a prospective, multi-center, single arm, phase II trial using docetaxel (75 mg/m(2), 60 min, d 1) and oxaliplatin (80 mg/m(2), 120 min, d 2) in 21-day cycles. The treatment period was scheduled for up to 8 cycles. Primary endpoint was tumor response according to RECIST 1.0. Secondary endpoints were progression free survival, overall survival, safety/toxicity, quality of life and clinical benefit. RESULTS: Data represent the intention to treat analysis of 44 patients with chemorefractory pancreatic cancer enrolled between 2008 and 2012 at five institutions in Germany. The primary endpoint of tumor response was achieved in 15.9% of the patients (7 partial remissions, no complete remission), with a disease control rate of 48% after the first two treatment cycles. Median progression free survival (PFS) was 1.82 months (CI 95% 1.5-3.96 months) and median overall survival (OS) was 10.1 months (CI 95% 5.1-14.1 months). CONCLUSIONS: This single-arm trial demonstrates that the combination of docetaxel and oxaliplatin yields promising results for the treatment of advanced pancreatic ductal adenocarcinoma patients. Selected patients had particular benefit from this treatment as indicated by long PFS and OS times. Even after 8 cycles of treatment with DocOx a partial response was observed in 2 patients and stable disease was observed in another 6 patients. The data obtained with the DocOx protocol compare well with other second line protocols such as OFF (oxaliplatin, 5-FU, leucovorin). The DocOx regimen could be an interesting option for patients who received gemcitabine as first line treatment for metastatic pancreatic cancer.

Phenotyping of peripheral blood mononuclear cells of patients with advanced heavily pre-treated adenocarcinoma of the stomach and gastro-esophageal junction.

Immunotherapeutic approaches are emerging as promising new treatment options for patients with solid cancers. The host immune system in cancer patients is dysfunctional due to a number of reasons. The level of immunosuppression is variable at the time of diagnosis and depends on the particular cancer entity, stage, and prior anti-cancer therapies. For many cancer entities, the immune alterations of the respective patient population have not been further characterized even though a patient's immunophenotype may be prognostic for the course of the disease or predictive for clinical/biological response to immunotherapy. In this study, we used flow cytometry to determine the phenotype of peripheral blood mononuclear cells (PBMCs) from 30 patients with heavily pre-treated, advanced adenocarcinoma of the stomach and gastro-esophageal junction. The frequencies and activation status of relevant immune effector populations were determined in PBMCs and compared to those of healthy individuals. This report provides comprehensive immune phenotyping data of a patient population with a high medical need.

Response to reintroduction of cetuximab in 5 patients with advanced, chemotherapy-resistant, colorectal cancer without progressive disease following first-line therapy with a cetuximab-containing regimen.

OBJECTIVE: We aimed to determine the response to cetuximab in advanced, chemotherapy-resistant, colorectal cancer following successful first-line therapy with the antibody. METHODS: Five patients with metastatic colorectal cancer were treated with a cetuximab-containing regimen after failure of several conventional chemotherapies. RESULTS: These patients had been successfully treated with cetuximab as first-line therapy, and the antibody was then discontinued without disease progression. No severe toxicities were observed upon reexposure to cetuximab. Partial response was noted in 1 patient and tumor stabilization in 2 patients. CONCLUSION: Reintroduction of cetuximab in combination with chemotherapy is safe and efficacious in patients with colorectal cancer whose tumors were not refractory to a prior cetuximab-containing therapy.

[Problems and chances of the application of systemically acting drugs via the lung]. / Möglichkeiten und Probleme der Applikation von systemisch wirksamen, höhermolekularen Wirkstoffen mittels Inhalation.

As a consequence of the development of drugs and other biologically active substances such as peptides or proteins, new ways of application for therapeutic use offer new therapeutic possibilities. Today, the predominant way of parenteral application is injection. Growing evidence suggests that some substances may be applied via inhalation. Nevertheless, inhalative application of drugs, although possible, is not very well supported by scientific data until now. This paper summarizes the present knowledge about transport of higher-molecular drugs across the pulmonary epithelium and deals with the problems of this method of application as well.

Tracheal and bronchial involvement in colitis ulcerosa - a colo-bronchitic syndrome? A case report and some additional considerations.

Systemic involvement is well known in patients with inflammatory bowel diseases (IBD), but there are only few data looking to Crohn's disease (CD) and ulcerative colitis (UC) separately instead of lumping together both entities to IBD. The frequency of bronchial involvement in UC is not yet exactly analysed but reported to be rare. We asked 100 patients with UC for bronchial complaints, and found in 13 patients a bronchial affection. From reports in the literature it is known that sometimes a bronchial involvement in patients with UC can affect the whole bronchial tree including small bronchi. The involvement of bronchial system in UC is obviously more prominent than previously thought and may fulfil the criteria for a separate syndrome. These relations may have consequences for pathogenetic understanding of UC as well as bronchitis and also consequences for treatment regimes.

A phase I/II study of oxaliplatin and paclitaxel in patients with non-resectable cancer of the oesophagus and adenocarcinoma of the gastro-oesophageal junction: a study of the Arbeitsgemeinschaft Internistische Onkologie.

PURPOSE: To assess the efficacy and toxicity of paclitaxel and oxaliplatin in patients with non-resectable cancer of the oesophagus and adenocarcinoma of the gastro-oesophageal junction. METHODS: Treatment consisted of oxaliplatin 85 mg/m(2) and paclitaxel 90 mg/m(2) on days 1, 15 and 29 every 6 weeks. Patients with a non-resectable cancer of the oesophagus and/or adenocarcinoma of the gastro-oesophageal junction were eligible. RESULTS: Twenty-six chemotherapy-naive patients were enrolled who had the following characteristics: median age 59.5 years (range 46-81); ECOG scores of 0/1/2 for 7/16/3 patients, respectively, and 23 (88%) patients had metastatic disease. There were 5 patients (19%) with adenocarcinoma of the gastro-oesophageal junction and 21 patients (81%) with oesophageal cancer; 19 (73%) had a squamous cell cancer and 7 (27%) had an adenocarcinoma. NCI grade 4 toxicity (neutropenia) was observed in one patient. Non-haematological toxicity consisted mainly of grade 1/2 neurosensory toxicity. The overall response rate by the intention-to-treat analysis was 15% with 4 patients having confirmed partial response. Overall tumour control rate was 73%. Median overall survival was 12.3 months (range 1.5-66) and median time to progression was 4.5 months (range 0.8-19.3). CONCLUSION: This regimen is well tolerated and demonstrates a modest response rate with a favourable disease control rate.