がん臨床試験ジャーナル

Heart disease can result from cancers and their treatment, heart failure being the case over time. This is however not our local experience as hardly we find heart failure patients with a past history of cancer or chemotherapy. We therefore decided to evaluate a cohort of patients on follow-up for haematological cancer therapy for cardiovascular status with a view to defining their heart disease burden. Thirteen patients (6 F) with age range of 18 to 55 years on follow-up for haematological cancers underwent cardiovascular examination and relevant data extracted from their files. None of them was in heart failure after a range of 1 to 3 years of therapy. Most however received Prednisolone as adjunctive treatment for their cancers namely: CLL, CML, ALL, AML and Hodgkin’s Lymphoma. The low rate of heart disease in our cohort of haematological cancers was surprising. Whether it is due to genetics, environmental factor or adjunctive treatment would require further studies to elucidate. Steroids being anti-inflammatory and anti-fibrotic may be countering inflammatory and fibrotic cardiac damage that chemotherapeutic agents cause.

Objective: High quality clinical trials are essential for further improvement of treatment strategies for prolonged survival and reliable evidence-based outcomes. However, there are no defined standards for the quality of clinical trial performance. The aim of this study is to examine and compare clinical trial performance with a composite score between (different types of) hospitals, to identify potentially predicting factors for a high trial performance and examine a learning curve in composite performance scores between early compared to subsequent included patients.

Methods: We evaluated trial performance in three large phase 3 randomized clinical trials in metastatic colorectal cancer (CAIRO studies of the Dutch Colorectal Cancer Group, total n=2131) with a newly introduced composite score, consisting of stratification errors, major protocol violations, number of included ineligible patients, and reporting of serious adverse events (SAE) on hospital and patient level. These data were supplemented with a hospital survey containing questions about number of beds, oncologists and research nurses. A logistic regression was performed to identify factors associated with better trial performance (3-4 points).

Results: We observed variation in trial performance between 84 participating hospitals. However, no differences in performance between hospital categories (university, teaching and regional hospitals) were identified and none of the examined variables could be linked to a high composite performance score. In top 10 ranking hospitals with highest inclusion rates, trial performance on patient level was significantly lower in the first three inclusions compared to subsequent patients..

Conclusions: Trial performance was comparable between different types of hospitals and no factors were able to predict a high composite trial performance score. In the highest including hospitals we identified a learning curve for trial performance. We therefore recommend increased support during the first patient inclusions in participating centres in order to improve trial performance. Our composite score could be used as a quality metric for trial performance for individually based hospital evaluation.

The highest risk of recurrence following therapy for early stage endometrial cancer is within 3 years, and the most frequent sites of recurrence are the vaginal vault and the pelvis.

We describe an unusual case of a patient with recurrent endometrial cancer to the wall of the sigmoid colon and adjacent lymph nodes, 15 years after radical therapy for early stage disease. The patient was treated by sigmoidectomy and adjuvant megesterol acetate. She is well more than 4 years thereafter.

Purpose: Connective tissue growth factor (CTGF) is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and facilitates local desmoplasia, tumor progression and metastasis in animal models. This study evaluated safety and initial efficacy of the anti-CTGF antibody FG-3019 in combination with gemcitabine and erlotinib in patients with previously untreated Stage III or Stage IV PDAC.

Methods: Eight escalating FG-3019 doses/regimens ranging from 3 to 45 mg/kg Q2W and 17.5 and 22.5 mg/kg QW were evaluated. Toxicity, tumor response by CA19.9 and CT scan RECIST criteria, progression-free and overall survival were assessed. FG-3019 day 15 trough plasma levels (D15Cmin), as a measure of exposure, and baseline CTGF levels were correlated with clinical outcomes.

Results: Seventy-five patients were enrolled over 39.6 months. Median and longest treatment duration were 3.3 and 20.9 months, respectively. FG-3019 was well tolerated with no dose-related trends observed in type or incidence of SAEs. No FG-3019- dose-liming toxicity was observed. Median PFS and OS were 3.7 and 7.4 months, respectively. High FG-3019 exposure (D15 Cmin ≥ 150 μg/mL), compared to low exposure, was associated with improved median OS (9.0 vs. 4.4 months, respectively, p=0.024), 1-year OS rate (34.2% vs. 10.8%, respectively, p=0.026), and median PFS (6.0 vs. 2.4 months, respectively, p=0.032). Plasma CTGF showed potential as a predictive biomarker, as low baseline CTGF levels (<10 ng/mL) were associated with improved OS (10.1 vs. 4.4 months, p=0.028); and PFS (5.5 vs. 2.3 months, p=0.019).

Conclusions: FG-3019 can be safely combined with gemcitabine and erlotinib without incremental toxicity in advanced pancreatic cancer patients. Low baseline CTGF and high FG-3019 exposure were associated with improved survival. Targeting of PDAC by FG-3019 in combination with cytotoxic chemotherapy represents a novel approach to this difficult disease and further trails are warranted.