Use of Systemic Therapy Concurrent With Cranial Radiotherapy for Cerebral Metastases of Solid Tumors.

The incidence of brain metastases of solid tumors is increasing. Local treatment of brain metastases is generally straightforward: cranial radiotherapy (e.g.

Severe fluoropyrimidine toxicity due to novel and rare DPYD missense mutations, deletion and genomic amplification affecting DPD activity and mRNA splicing.

Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (5FU). Genetic variations in DPD have emerged as predictive risk factors for severe fluoropyrimidine toxicity. Here, we report novel and rare genetic variants underlying DPD deficiency in 9 cancer patients presenting with severe fluoropyrimidine-associated toxicity.

A phase I-II study on the combination of rapamycin and short course radiotherapy in rectal cancer.

Purpose: This phase I/II study sought to determine the safety and maximum tolerated dose (MTD) of the combination of rapamycin, an mTOR inhibitor, with short-course radiotherapy in rectal cancer patients. Antitumor activity, changes in metabolic activity and perfusion on imaging, and changes in phosphorylation status of the mTOR pathway were also assessed.

Materials And Methods: Patients with primary resectable rectal cancer were treated with short-course hypofractionated radiotherapy (5×5 Gy) combined with oral rapamycin 1 week before and during radiotherapy, followed by surgical resection.

Neo-adjuvant chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases: the CHARISMA randomized multicenter clinical trial.

Background: Efforts to improve the outcome of liver surgery by combining curative resection with chemotherapy have failed to demonstrate definite overall survival benefit. This may partly be due to the fact that these studies often involve strict inclusion criteria. Consequently, patients with a high risk profile as characterized by Fong's Clinical Risk Score (CRS) are often underrepresented in these studies.

Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group.

Background: The optimum duration of first-line treatment with chemotherapy in combination with bevacizumab in patients with metastatic colorectal cancer is unknown. The CAIRO3 study was designed to determine the efficacy of maintenance treatment with capecitabine plus bevacizumab versus observation.

Methods: In this open-label, phase 3, randomised controlled trial, we recruited patients in 64 hospitals in the Netherlands.

Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial.

Background: Treatment options for recurrent glioblastoma are scarce, with second-line chemotherapy showing only modest activity against the tumour. Despite the absence of well controlled trials, bevacizumab is widely used in the treatment of recurrent glioblastoma. Nonetheless, whether the high response rates reported after treatment with this drug translate into an overall survival benefit remains unclear.

Lactate dehydrogenase as a selection criterion for ipilimumab treatment in metastatic melanoma.

Introduction: Ipilimumab, a cytotoxic T lymphocyte-associated antigen-4 blocking antibody, has improved overall survival (OS) in metastatic melanoma in phase III trials. However, about 80 % of patients fail to respond, and no predictive markers for benefit from therapy have been identified. We analysed a 'real world' population of patients treated with ipilimumab to identify markers for treatment benefit.

Phase I trial of the combination of the Akt inhibitor nelfinavir and chemoradiation for locally advanced rectal cancer.

Purpose: To investigate the toxicity of nelfinavir, administered during preoperative chemoradiotherapy (CRT) in patients with locally advanced rectal cancer.

Material And Methods: Twelve patients were treated with chemoradiotherapy to 50.4 Gy combined with capecitabine 825 mg/m(2) BID.

Hyaluronic acid as a marker of hepatic sinusoidal obstruction syndrome secondary to oxaliplatin-based chemotherapy in patients with colorectal liver metastases.

Background: A considerable number of patients develop sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy for colorectal liver metastases (CLMs). SOS is associated with adverse outcomes after major hepatectomy. Hyaluronic acid (HA) is a marker of hepatic sinusoidal endothelial cell function and may serve as an accurate marker of SOS.

Which way is forward in the treatment of rectal cancer?

Preoperative 5-fluorouracil-based chemoradiation with optimal surgery provides very effective local control in locally advanced rectal cancer. Does adding oxaliplatin as a radiosensitizer provide any additional benefit? Is more always better?

Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer.

Purpose: Neoadjuvant chemoradiotherapy for rectal cancer can result in complete disappearance of tumor and involved nodes. In patients without residual tumor on imaging and endoscopy (clinical complete response [cCR]) a wait-and-see-policy (omission of surgery with follow-up) might be considered instead of surgery. The purpose of this prospective cohort study was to evaluate feasibility and safety of a wait-and-see policy with strict selection criteria and follow-up.

Weekly infusional high-dose fluorouracil (HD-FU), HD-FU plus folinic acid (HD-FU/FA), or HD-FU/FA plus biweekly cisplatin in advanced gastric cancer: randomized phase II trial 40953 of the European Organisation for Research and Treatment of Cancer Gastrointestinal Group and the Arbeitsgemeinschaft Internistische Onkologie.

Purpose: This multicentric, randomized, two-stage phase II trial evaluated three simplified weekly infusional regimens of fluorouracil (FU) or FU plus folinic acid (FA) and cisplatin (Cis) with the aim to select a regimen for future phase III trials.

Patients And Methods: A total of 145 patients with advanced gastric cancer where randomly assigned to weekly FU 3,000 mg/m2/24 hours (HD-FU), FU 2,600 mg/m2/24 hours plus dl-FA 500 mg/m2 or l-FA 250 mg/m2 (HD-FU/FA), or FU 2000 mg/m2/24 hours plus FA plus biweekly Cis 50 mg/m2, each administered for 6 weeks with a 1-week rest. The primary end point was the response rate.

Pharmacogenetic screening of CYP3A and ABCB1 in relation to population pharmacokinetics of docetaxel.

Purpose: Despite the extensive clinical experience with docetaxel, unpredictable interindividual variability in efficacy and toxicity remain important limitations associated with the use of this anticancer drug. Large interindividual pharmacokinetic variability has been associated with variation in toxicity profiles. Genetic polymorphisms in drug-metabolizing enzymes and drug transporters could possibly explain the observed pharmacokinetic variability.

Clinical and immunohistochemical analysis of patients with unknown primary tumour. A search for prognostic factors in UPT.

Background: The unknown primary tumour (UPT) is an intriguing clinical finding in approximately 5% of all newly diagnosed patients with cancer. To evaluate a correlation between the specific immunohistochemical alterations in UPT cells and the unique clinical features of UPT patients, to define the natural history of UPT and to verify prognostic factors, we undertook a detailed clinical and immunohistochemical analysis of patients with the diagnosis of adenocarcinoma of UPT.

Results: Patients with UPT present with a short history and have a poor prognosis.