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.

p16 expression differentiates high-risk gastrointestinal stromal tumor and predicts poor outcome.

Gastrointestinal stromal tumors (GISTs) are characterized by alterations in genes involved in cell cycle regulation. Although p16 (INK4A) have been extensively investigated in GISTs, there are still discrepancies regarding its prognostic value. Therefore, we evaluated the clinical occurrence, diagnostic and prognostic value of p16 staining in GIST. One hundred one patients (54 women and 47 men) with a mean age of 64.1 years (range, 17-94 years) were surgically treated for a GIST within a 10-year period. Of these patients, 28 (28%) were affected by metastases (mean follow-up, 4.5 years). In 36 patients (36%), GIST occurred coincidentally with other malignancies. Expression of c-kit was confirmed in 97 GIST patients (96%). In patients with high-risk GIST, the expression of p16 expression was highly predictive for poor prognosis, i.e., the development of recurrence or metastases (P = .006) and poor survival (P = .004). In addition, the expression of p16 was highly predictive for reduction of the survival in patients who were affected by metastases or recurrence (P = .041). The disease-specific and disease-free 1-, 3-, and 5-year survival rate was 96%, 90%, and 85% and 81%, 77%, and 72%, respectively. Primary tumor state, tumor size, and high-risk classification were confirmed as relevant predictors for unfavorable prognosis in GIST (P < .001). Our results indicate that in high-risk GIST and in patients with recurrence or metastases, the expression of p16 is highly predictive for poor outcome. Thus, in addition to high-risk classification, p16 expression might be an indicator for "very high risk GIST."

[No effect of spironolactone on bulimia nervosa symptoms]. / Keine Wirkung von Spironolacton auf Symptome der Bulimia nervosa--Ergebnisse einer kontrollierten, randomisierten Studie.

Some case reports mention that Spironolactone, a mineral corticoid antagonist and aldosterone antagonist, reduces binging in patients with bulimia nervosa. Therefore, we decided to study these findings by using a randomized, double-blind, placebo controlled study design. In one study arm, patients with bulimia nervosa were treated with 150 mg Spironolactone per day; in the other arm, patients received a placebo for a total of 8 weeks. The target variables were the number of binges and the bulimia scale of the Eating Disorder Inventory. The study included 93 patients. The results show that the number of binges and the scores on the bulimia scale decreased somewhat, but this occurred in both groups. We were not able to show any significant statistical differences between the Spironolactone group and the placebo group. Additional evaluations, executed with data from the Symptom-Check-List (SCL-90R) and with other scales from the EDI-2 also showed no effect of Spironolactone. Therefore, a treatment with Spironolactone seems to have no effect on bulimia nervosa symptoms.

The impact of economic progress and modernization in medicine on the ossification of hand and wrist.

One of the main criteria used for age estimations of young living subjects is the developmental status of the ossification of hand bones. The impact of economic progress and modernization in medicine on ossification rates in a given population still requires further clarification. We selected 36 samples from literature for which the ossification status had been determined with the Greulich-Pyle method and analyzed specific economic data (per capita income) and demographic data (life expectancy at birth) as parameters of modernization. To describe the influence of these parameters on the rate of ossification, we performed a regression analysis and found that a relatively high level of economic progress and modernization in medicine coincides with high ossification rates, while relatively low modernization seems to delay ossification. When performing age estimations, the expert opinion should therefore pay attention to the issue of different modernization levels.