A phase II study of a human anti-PDGFRα monoclonal antibody (olaratumab, IMC-3G3) in previously treated patients with metastatic gastrointestinal stromal tumors.

Background: This study evaluated tumor response to olaratumab (an anti-PDGFRα monoclonal antibody) in previously treated patients with metastatic gastrointestinal stromal tumor (GIST) with or without PDGFRα mutations (cohorts 1 and 2, respectively). Patients and methods: Patients received olaratumab 20 mg/kg intravenously every 14 days until disease progression, death, or intolerable toxicity occurred. Outcome measures were 12-week tumor response, progression-free survival (PFS), overall survival (OS), and safety. Results: Of 30 patients enrolled, 21 patients received ≥1 dose of olaratumab. In the evaluable population (cohort 1, n = 6; cohort 2, n = 14), no complete response (CR) or partial response (PR) was observed. Stable disease (SD) was observed in 3 patients (50.0%) in cohort 1 and 2 patients (14.3%) in cohort 2. Progressive disease (PD) was observed in 3 patients (50.0%) in cohort 1 and 12 patients (85.7%) in cohort 2. The 12-week clinical benefit rate (CR + PR + SD) (90% CI) was 50.0% (15.3-84.7%) in cohort 1 and 14.3% (2.6-38.5%) in cohort 2. SD lasted beyond 12 weeks in 5 patients (cohort 1, n = 3; cohort 2, n = 2). Median PFS (90% CI) was 32.1 (5.0-35.9) weeks in cohort 1 and 6.1 (5.7-6.3) weeks in cohort 2. Median OS was not reached in cohort 1 and was 24.9 (14.4-49.1) weeks in cohort 2. All patients in cohort 1 and 9 (64.3%) in cohort 2 experienced an olaratumab-related adverse event (AE), most commonly fatigue (38.1%), nausea (19.0%), and peripheral edema (14.3%). Two grade ≥3 olaratumab-related events were reported (cohort 1, syncope; cohort 2, hypertension). Conclusions: Olaratumab had an acceptable AE profile in patients with GIST. While there was no apparent effect on PFS in patients without PDGFRα mutations, patients with PDGFRα-mutant GIST (all with D842V mutations) treated with olaratumab had longer disease control compared with historical data for this genotype. ClinicalTrials.gov Identifier: NCT01316263.

[Chemotherapy of hormone refractory prostate carcinoma]. / Chemotherapie beim hormonrefraktären Prostatakarzinom.

An increasing life expectancy and the growing number of largely healthy older men have lead to more patients with hormone insensitive relapses after palliative hormone or curative therapy for prostate cancer. After 10 years without therapeutic improvement for hormone refractory prostate cancer, the introduction of new substances has led to a revival of chemotherapy. Although a definitive cure is still not possible, such chemotherapy fulfils important palliative criteria-good toleration and an improvement in quality of life-in addition to distinct long-term remission. For example, taxane as a monotherapy or in combination with estramustine is effective and well tolerated while mitoxantrone in combination with prednisolone, although of limited effectiveness, leads to a substantial reduction in symptoms. Although evidence for increased longevity through modern chemotherapy is available, this has still not been definitively demonstrated. The substantial reduction in pain and therapy related morbidity frequently makes chemotherapy for hormone refractive prostate cancer a superior alternative to simple pain and complication management.

[Syndrome of persisting mullerian duct with first manifestation in an adult]. / Syndrom des persistierenden Müller-Ganges mit Erstmanifestation beim Erwachsenen.

INTRODUCTION: We report on a 22-year-old male patient who presented with an intrapelvic tumor. CASE REPORT: CT and MRI showed a left pelvic abscess, which was drained. After regression of the abscess, we removed the causative tubular structure surgically, revealing a rudimentary genital structure with parts of the Mullerian and Wolffian ducts. CONCLUSIONS: This case report demonstrates an abscess formation as complication of a previously asymptomatic rudimentary genital structure, which was associated with further abnormalities, such as left testicular agenesia, perineoscrotal hypospadias and transverse testicular ectopia.

Spontaneous late rupture of orthotopic detubularized ileal neobladders: report of five cases.

OBJECTIVES: To report five spontaneous ruptures in 4 patients. Spontaneous late rupture of orthotopic ileal bladder replacements is a rare complication of continent urinary diversion. METHODS: Four recurrence-free patients aged 36 to 68 years experienced apparently spontaneous rupture of continent orthotopic ileal bladder replacement 3 months to 3 years after curative radical cystectomy and urinary diversion for invasive bladder cancer. Ileal bladder rupture occurred twice in 1 patient with an interval of 9 months. RESULTS: All 4 patients had had a good result from their diversion procedure and had reported complete day and nighttime continence before the spontaneous rupture. The spontaneous rupture was evidently caused by overdistension of the ileal neobladder in four of five instances. In addition to overdistension, a second factor such as minor blunt abdominal trauma or urethral occlusion was identifiable in two instances. The rupture occurred in the right upper corner of the ileal bladder in four of five instances and led to acute and severe abdominal pain. Cystography was done in three instances, but was diagnostic in only 2 cases. The histologic examination of the excised bladder wall margins revealed nonspecific inflammatory changes in 3 cases. Open surgical drainage and repair was successfully undertaken in all cases. CONCLUSIONS: The circumstances of the cases described suggest that late spontaneous rupture of an orthotopic ileal bladder replacement is not related to the surgical technique but rather to factors of patient compliance and medical management.