Enzalutamide Reduces Oxycodone Exposure in Men with Prostate Cancer.

Background And Objective: Up to 90% of patients with castration-resistant prostate cancer (CRPC) will develop symptomatic bone metastases requiring pain medication, with opioids being the mainstay of therapy in treating moderate and severe pain. Enzalutamide is an androgen receptor antagonist for the treatment of CRPC and a strong inducer of cytochrome P450 (CYP)3A4. Hereby, enzalutamide potentially reduces the exposure of oxycodone, an opioid metabolized by CYP3A4 and CYP2D6.

Lean Body Mass and Total Body Weight Versus Body Surface Area as a Determinant of Docetaxel Pharmacokinetics and Toxicity.

Aim: This study examined whether anthropometric and body composition parameters such as body surface area (BSA), lean body mass (LBM), and total body weight (TBW) are correlated with docetaxel clearance and exposure by analyzing area under the curve. In addition, LBM, TBW, and a fixed dose were compared with BSA as dosing parameters for dose individualization of docetaxel.

Methods: Thirty-six patients receiving docetaxel chemotherapy for breast or metastatic castration-resistant prostate carcinoma were included.

The impact of a 1-hour time interval between pazopanib and subsequent intake of gastric acid suppressants on pazopanib exposure.

Co-treatment with gastric acid suppressants (GAS) in patients taking anticancer drugs that exhibit pH-dependant absorption may lead to decreased drug exposure and may hamper drug efficacy. In our study, we investigated whether a 1-hour time interval between subsequent intake of pazopanib and GAS could mitigate this negative effect on drug exposure. We performed an observational study in which we collected the first steady-state pazopanib trough concentration (C ) levels from patients treated with pazopanib 800 mg once daily (OD) taken fasted or pazopanib 600 mg OD taken with food.

Third-line Life-prolonging Drug Treatment in a Real-world Metastatic Castration-resistant Prostate Cancer Population: Results from the Dutch Castration-resistant Prostate Cancer Registry.

Background: Evidence concerning third-line life-prolonging drugs (LPDs) in the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients is incomplete.

Objective: To evaluate third-line LPD outcomes in a real-world cohort of mCRPC patients, identify variables associated with overall survival (OS), and establish a prognostic model.

Design, Setting, And Participants: Patients with mCRPC who were progressive on second-line LPD before July 1, 2017 were retrospectively identified from the Dutch Castration-resistant Prostate Cancer Registry (CAPRI) and followed until December 31, 2017.

The Effect of Using Pazopanib With Food vs. Fasted on Pharmacokinetics, Patient Safety, and Preference (DIET Study).

Pazopanib is taken fasted in a fixed oral daily dose of 800 mg. We hypothesized that ingesting pazopanib with food may improve patients' comfort and reduce gastrointestinal (GI) adverse events. Therefore, we investigated the bioequivalent dose of pazopanib when taken with food compared with 800 mg pazopanib taken fasted.

A randomised phase II trial of docetaxel versus docetaxel plus carboplatin in patients with castration-resistant prostate cancer who have progressed after response to prior docetaxel chemotherapy: The RECARDO trial.

Background: Docetaxel is standard first-line chemotherapy for patients with metastatic castration-resistant prostate carcinoma (mCRPC). Docetaxel re-challenge has never been tested in a prospective randomised controlled study. As some studies support the addition of carboplatin to docetaxel, we performed a phase II trial investigating the combination of docetaxel plus carboplatin versus docetaxel re-treatment in docetaxel pre-treated mCRPC patients.

SWITCH: A Randomised, Sequential, Open-label Study to Evaluate the Efficacy and Safety of Sorafenib-sunitinib Versus Sunitinib-sorafenib in the Treatment of Metastatic Renal Cell Cancer.

Background: Understanding how to sequence targeted therapies for metastatic renal cell carcinoma (mRCC) is important for maximisation of clinical benefit.

Objectives: To prospectively evaluate sequential use of the multikinase inhibitors sorafenib followed by sunitinib (So-Su) versus sunitinib followed by sorafenib (Su-So) in patients with mRCC.

Design, Setting, And Participants: The multicentre, randomised, open-label, phase 3 SWITCH study assessed So-Su versus Su-So in patients with mRCC without prior systemic therapy, and stratified by Memorial Sloan Kettering Cancer Center risk score (favourable or intermediate).

Phase II trial of Uracil/Tegafur plus leucovorin and celecoxib combined with radiotherapy in locally advanced pancreatic cancer.

Background And Purpose: To investigate the efficacy and toxicity of a short intensive Uracil/Tegafur (UFT) based chemoradiotherapy scheme combined with celecoxib in locally advanced pancreatic cancer.

Material And Methods: The Academic Medical Centre, Amsterdam and the Erasmus Medical Centre, Rotterdam enrolled 83 eligible patients with unresectable pancreatic cancer in a prospective multicentre phase II study. Median age was 62 years, median tumour size 40 mm and the majority of the patients (85%) had pancreatic head cancers.

Randomized double-blind phase II trial comparing gemcitabine plus LY293111 versus gemcitabine plus placebo in advanced adenocarcinoma of the pancreas.

Background: LY293111 (LY) is a novel oral anticancer agent with leukotriene B4 receptor antagonist and peroxisome proliferator-activated receptor gamma agonist properties, producing promising results alone and in combination with gemcitabine in pancreatic cancer xenograft models. A phase I study proved that the combination (gemcitabine plus LY) is safe and well tolerated.

Patients And Methods: Chemotherapy-naive patients with histologically confirmed locally advanced or metastatic adenocarcinoma of the pancreas were randomly assigned to gemcitabine 1000 mg/m on days 1, 8, and 15 of a 28-day cycle and continuously administered LY 600 mg twice daily or gemcitabine 1000 mg/m on days 1, 8, and 15 of a 28-day cycle and daily oral placebo.

Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer.

Purpose: Treatment with gemcitabine provides modest benefits in patients with metastatic pancreatic cancer. The addition of erlotinib to gemcitabine shows a small but significant improvement in overall survival (OS) versus gemcitabine alone. Phase II results for bevacizumab plus gemcitabine provided the rationale for a phase III trial of gemcitabine-erlotinib plus bevacizumab or placebo.

Differential responses of cellular immunity in patients undergoing neoadjuvant therapy followed by surgery for carcinoma of the oesophagus.

Background: To compare immune responses following neoadjuvant chemoradiation therapy in combination with hyperthermia plus surgery to those induced by surgery alone in patients with oesophageal cancer.

Methods: Thirty-two patients with histopathologically proven oesophageal cancer, scheduled for potentially curative transhiatal or transthoracic oesophagectomy with (neo, n = 20) or without (control, n = 12) neoadjuvant thermochemoradiation therapy (ThCR) were included. Peripheral blood samples were obtained before ThCR, after 2 weeks of ThCR, 1 day before surgery, on postoperative days 1, 3, 7, and 6 weeks after surgery, for white blood cell counts, lymphocyte subsets and T helper type 1 (Th1) and type 2 (Th2) lymphocyte responses.

Giant rectal gastrointestinal stromal tumors: a report of two cases.

Giant gastrointestinal stromal tumors (GISTs) of the rectum are rare and often difficult to remove surgically. At the time metastases are found, GISTs are considered to be incurable and until recently no adequate therapy was of any value for these patients. Recently, imatinib was introduced: a signal transducing inhibitor acting specifically on the KIT-tyrosine kinase, which can be used to downsize giant GIST (neo-adjuvant) before surgery or induce stable disease in case of metastases with few minor side-effects.

Phase I pharmacokinetic study of the safety and tolerability of lapatinib (GW572016) in combination with oxaliplatin/fluorouracil/leucovorin (FOLFOX4) in patients with solid tumors.

Purpose: This phase I study was designed to determine the optimally tolerated regimen (OTR), safety, and clinical activity of lapatinib in combination with FOLFOX4 [oxaliplatin/leucovorin/5-fluorouracil (5-FU)] in patients with solid tumors. Furthermore, the pharmacokinetics of lapatinib, oxaliplatin, and 5-FU when given alone and in combination were evaluated.

Experimental Design: This study was conducted in two parts.

Radiopharmaceutical management of 90Y/111In labeled antibodies: shielding and quantification during preparation and administration.

Background: The combined application of potent beta-emitting isotopes for therapy with remitting isotopes for scintigraphy requires a profound regimen concerning team member safety and radionuclide quantification.

Methods: We have developed materials and methods for a proper and easy manipulation of 90Y during preparation and administration of 90Y/111In pharmaceuticals used for radioimmunotherapy.

Results: The efficacy of the shielding measures is documented.

Monitoring of response to pre-operative chemoradiation in combination with hyperthermia in oesophageal cancer by FDG-PET.

Purpose: To evaluate the use of positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) to assess early response to pre-operative chemoradiation therapy in combination with external locoregional hyperthermia in patients with oesophageal cancer by correlating the reduction of metabolic activity with histopathologic response.

Material And Methods: Twenty-six patients with histopathologically proven intra-thoracic oesophageal cancer (with < or =2 cm gastric involvement), scheduled to undergo a 5-week course of pre-operative chemoradiation therapy and hyperthermia, were included. FDG-PET was performed before (n = 26) and 2 weeks after initiation of therapy (n = 17).

Predictive factors for outcome in a phase II study of gefitinib in second-line treatment of advanced esophageal cancer patients.

Purpose: The efficacy of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib was assessed in a phase II study in patients with advanced esophageal cancer. Several biologic features were investigated as potential markers of gefitinib activity.

Patients And Methods: Patients with advanced esophageal cancer, who had failed one line of prior chemotherapy, were administered gefitinib 500 mg/d.

Systemic treatment of oesophageal cancer.

Most patients with oesophageal cancer present with locally advanced or metastatic disease. In an effort to improve the results of surgery in patients with operable disease, strategies to incorporate radiotherapy and chemotherapy, preoperatively (neoadjuvant) and postoperatively (adjuvant), have been extensively investigated in numerous clinical trials. Meta-analyses of neoadjuvant trials did not demonstrate a survival advantage for neoadjuvant chemotherapy or concurrent chemoradiotherapy.

Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer.

Purpose: To determine whether addition of the farnesyltransferase inhibitor tipifarnib (Zarnestra, R115777; Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium) to standard gemcitabine therapy improves overall survival in advanced pancreatic cancer.

Patients And Methods: This randomized, double-blind, placebo-controlled study compared gemcitabine + tipifarnib versus gemcitabine + placebo in patients with advanced pancreatic adenocarcinoma previously untreated with systemic therapy. Tipifarnib was given at 200 mg bid orally continuously; gemcitabine was given at 1,000 mg/m(2) intravenously weekly x 7 for 8 weeks, then weekly x 3 every 4 weeks.

Farnesyl protein transferase inhibition interferes with activation of MAP kinase family members in human peripheral blood monocytes.

Background: Farnesyl protein transferase inhibitors have emerged as promising novel agents for combating cancerous disease. Nevertheless, the importance for farnesyl protein transferase enzymatic activity for cellular physiology of untransformed cells remains poorly investigated.

Materials And Methods: Peripheral blood monocytes, isolated from the blood of eight healthy volunteers, were treated with a farnesyl protein transferase inhibitor (FTI 744,832) or vehicle control for 16 hr.

[Malignant intracranial germ cell tumor treated with chemotherapy and radiotherapy without histopathological confirmation].

In two men aged 19 and 24 years, a rare malignant intracranial germ cell tumour was diagnosed in the pineal gland region and in the second patient in a suprasellar position as well. Although histological confirmation is required in general to diagnose a malignancy, obtaining it can be difficult and potentially dangerous in case of intracranial neoplasms. The clinical picture of a young patient with an intracerebral tumour localised in the midline of the brain and increased levels of the tumour markers alpha-foetoprotein and/or human chorion gonadotrophin (beta-HCG) in blood and/or CSF makes any other diagnosis highly unlikely.