Sorafenib alone vs. sorafenib plus GEMOX as 1-line treatment for advanced HCC: the phase II randomised PRODIGE 10 trial.

Background: Sorafenib remains one major first-line therapeutic options for advanced hepatocellular carcinoma (aHCC), with modest efficacy. We investigated the addition of gemcitabine and oxaliplatin (GEMOX) to sorafenib in aHCC patients.

Methods: Our multicentre phase II trial randomised aHCC first-line patients to sorafenib (400 mg BID) or sorafenib-GEMOX every 2 weeks (1000 mg/m gemcitabine; 100 mg/m oxaliplatin).

Management of Cancer Cachexia and Guidelines Implementation in a Comprehensive Cancer Center: A Physician-Led Cancer Nutrition Program Adapted to the Practices of a Country.

Context: Cancer-associated cachexia is correlated with survival, side-effects, and alteration of the patients' well-being.

Objectives: We implemented an institution-wide multidisciplinary supportive care team, a Cancer Nutrition Program (CNP), to screen and manage cachexia in accordance with the guidelines and evaluated the impact of this new organization on nutritional care and funding.

Methods: We estimated the workload associated with nutrition assessment and cachexia-related interventions and audited our clinical practice.

Sorafenib and irinotecan (NEXIRI) as second- or later-line treatment for patients with metastatic colorectal cancer and KRAS-mutated tumours: a multicentre Phase I/II trial.

Background: This trial evaluated the feasibility and efficacy of combined sorafenib and irinotecan (NEXIRI) as second- or later-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC), who had progressed after irinotecan-based chemotherapy.

Methods: In Phase I, in a 3+3 dose escalation schedule, patients received irinotecan (125, 150 or 180 mg m(-2) every 2 weeks), in combination with 400 mg sorafenib b.d.

Versatile UCST-based thermoresponsive hydrogels for loco-regional sustained drug delivery.

Poly(N-acryloyl glycinamide) is a neutral polymer that can form gel-sol thermoresponsive systems with upper critical solution temperature in aqueous media. The temperature of the reversible gel-sol transition depends on the molar mass and the concentration of macromolecules. These parameters were combined to adjust the transition temperature slightly above body temperature for the sake of respecting living tissues during the sol form injection using a classical syringe.

Stability of the ready-to-use solutions of eribulin for intravenous infusion.

A simple HPLC-UV method was developed to determine the stability of ready-to-use eribulin solutions under different storage conditions. The developed method was validated with respect to linearity, accuracy, precision and ruggedness. The following admixtures were prepared: 3-mL polypropylene syringes at concentration of 440 μg/mL and multilayer laminate polyolefin containers containing 0.

Stability of ready-to-use temsirolimus infusion solution (100mg/L) in polypropylene containers under different storage conditions.

The aim of this study was to determine the stability of ready-to-use temsirolimus infusion solutions under different storage conditions. Solutions were prepared in polypropylene containers by adding temsirolimus injection to 0.9% sodium chloride infusion to reach a final concentration of 100mg/L.

Permanent scalp alopecia related to breast cancer chemotherapy by sequential fluorouracil/epirubicin/cyclophosphamide (FEC) and docetaxel: a prospective study of 20 patients.

Background: To analyze the clinical and histological features of permanent alopecia following a sequential fluorouracil/epirubicin/cyclophosphamide (FEC) and docetaxel regimen for adjuvant breast cancer treatment.

Patients And Methods: Women treated for breast cancer by a sequential adjuvant FEC and docetaxel regimen who developed permanent alopecia diagnosed between 2007 and 2011 were identified from the Department of Dermatology (Saint-Eloi Hospital, Montpellier, France) and the Department of Medical Oncology (CRLC Val d'Aurelle, Montpellier, France). Data were collected regarding demographics, type of cancer, delay of onset after chemotherapy, Dermatology Life Quality Index (DLQI), clinical description of the lesions, scalp biopsies, laboratory explorations investigating steroid hormonal, iron, zinc and thyroid status, therapy and outcome.

Feasibility of biweekly combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in patients with metastatic solid tumors: results of a two-step phase I trial: XELIRI and XELIRINOX.

Background: Biweekly schedule of capecitabine combined with irinotecan (XELIRI), consecutively with irinotecan and oxaliplatin (XELIRINOX), was evaluated in patients with metastatic cancer from any solid tumors.

Patients And Methods: In this two-step phase I trial, seventeen and eleven patients were enrolled in the XELIRI and XELIRINOX stages, respectively.

Results: In XELIRI, a total of 136 chemotherapy cycles were administered with a median number of 8 cycles per patient (2-16).

Intraperitoneal administration of novel doxorubicin loaded polymeric delivery systems against peritoneal carcinomatosis: experimental study in a murine model of ovarian cancer.

Objective: Peritoneal spread is an adverse outcome in ovarian cancer. Despite clinical efficiency, intraperitoneal (i.p.

Etoposide, mitomycin, and methotrexate combination in heavily treated breast cancer: a retrospective study.

Background: Since 2004, metastatic breast cancer patients pretreated with anthracyclines, taxanes, and capecitabine have been treated in our institution with a combination of mitomycin C, methotrexate, and VP-16 (VMM). We report in this study a retrospective analysis of the activity and safety of the VMM combination.

Methods: Patients were treated with a combination of VP-16 (100 mg/m2 on day 1), mitomycin C (MMC, 10 mg/m2 on day 1), and methotrexate (MTX, 12.

Clinical impact of intesified 5-Fluorouracil-based chemotherapy using a prospective pharmacokinetically-guided dosing approach: comparative study in elderly and non-elderly patients with metastatic colorectal cancer.

We compared clinical outcome and pharmacokinetic (pK) parameters of a new pharmacokinetically-guided dosing strategy in two groups of patients (age < or >65 years) with metastatic colorectal cancer (mCRC). We retrospectively analyzed all the patients with mCRC, receiving standard LV5FU2 regimen during cycle-1, intensified from cycle-2 onwards according to an adaptation schedule based on the area under the concentration-time curve (AUC) value (mg.h/l.

Carmustine and methotrexate in combination after whole brain radiation therapy in breast cancer patients presenting with brain metastases: a retrospective study.

Background: Since 1999, patients presenting with brain metastases (BM) from breast cancer (BC) are treated in our institution with a carmustine (BCNU)--methotrexate (MTX) combination. We report here our clinical experience regarding this combination.

Patients And Methods: Patients were treated by a combination of BCNU 100 mg/m(2) on day 1 and MTX 600 mg/m(2) on day 1 and 15 of a 28 day cycle.

Pregnane X Receptor (PXR) expression in colorectal cancer cells restricts irinotecan chemosensitivity through enhanced SN-38 glucuronidation.

Background: Clinical efficacy of chemotherapy in colorectal cancer is subjected to broad inter-individual variations leading to the inability to predict outcome and toxicity. The topoisomerase I inhibitor irinotecan (CPT-11) is worldwide approved for the treatment of metastatic colorectal cancer and undergoes extensive peripheral and tumoral metabolism. PXR is a xenoreceptor activated by many drugs and environmental compounds regulating the expression of drug metabolism and transport genes in detoxification organs such as liver and gastrointestinal tract.

Physicochemical stability of oxaliplatin in 5% dextrose injection stored in polyvinyl chloride, polyethylene, and polypropylene infusion bags.

Purpose: The physicochemical stability of extemporaneous dilutions of oxaliplatin in 5% dextrose injection stored in polyvinyl chloride (PVC), polypropylene, and polyethylene infusion bags was studied.

Methods: Oxaliplatin 100 mg/20 mL concentrated solution was diluted in 100 mL of 5% dextrose injection in PVC, polypropylene, and polyethylene infusion bags to produce nominal oxaliplatin concentrations of 0.2 and 1.

A limited sampling strategy to estimate the pharmacokinetic parameters of irinotecan and its active metabolite, SN-38, in patients with metastatic digestive cancer receiving the FOLFIRI regimen.

In this study we propose for the first time a limited sampling strategy to estimate the individual pharmacokinetic parameters of both irinotecan and SN-38 in patients treated with the irinotecan plus 5-fluorouracil (FOLFIRI) regimen. The pharmacokinetics of irinotecan and SN-38 were studied in 74 patients with advanced inoperable digestive cancer. Plasma concentrations were taken during and up to the 42 h following a 90-min infusion of irinotecan (180-225 mg/m(2)).

Biodistribution of doxorubicin-alkylated poly(L-lysine citramide imide) conjugates in an experimental model of peritoneal carcinomatosis after intraperitoneal administration.

Peritoneal spread is a common manifestation in ovarian and gastrointestinal cancer. Intraperitoneal (i.p.

Multicentre phase II study using increasing doses of irinotecan combined with a simplified LV5FU2 regimen in metastatic colorectal cancer.

Purpose: Irinotecan at 180 mg/m2 combined with an infusional 5-fluorouracil/leucovorin (5-FU/LV) regimen (FOLFIRI) is a standard first line therapy for metastatic colorectal cancer (mCRC). This phase II study aimed to assess whether increasing the irinotecan dose in the first line FOLFIRI regimen would benefit mCRC patients.

Patients And Methods: Patients received FOLFIRI every 2 weeks for up to six cycles, comprising a 5-FU/LV regimen combined with irinotecan at 180 mg/m2 (cycle 1), increasing to 220 mg/m2 (cycle 2) and 260 mg/m2 (cycle 3 and subsequent cycles) dependent on toxicity.

In vitro cytotoxic effect of melphalan and pilot phase II study in hormone-refractory prostate cancer.

The objective of this study was to determine the impact of single versus sequential exposure to melphalan on the proliferation of an androgen-independent prostate cell line, PC-3, and to report the results of a pilot phase II study. For exposure to a single bolus dose, the doses were added at the start of the study and cell culture was continued for 96 h. For sequential exposure, 1/9 of the dose was added every 1.

Pharmacokinetics and pharmacodynamics of irinotecan and its metabolites from plasma and saliva data in patients with metastatic digestive cancer receiving Folfiri regimen.

Purpose: Irinotecan is extensively metabolized into at least four compounds and previous pharmacokinetic-pharmacodynamic studies have given varying results. We hypothesized that saliva, a noninvasive, safe and painless biological sampling process, could be a good predictor of the behavior of irinotecan and its metabolites.

Methods: Thirty-five patients with metastatic digestive cancer were treated with a Folfiri regimen every 2 weeks.

Inter- and intraindividual variabilities in pharmacokinetics of fentanyl after repeated 72-hour transdermal applications in cancer pain patients.

Perception of pain by the patient is frequently one of the early signs preceding a diagnosis of cancer and, later, a sinister sign of disease progression. Among opioid drugs, transdermal fentanyl has been evaluated in the treatment of moderate to severe cancer pain. The objective of this study was to investigate the intra- and interindividual variabilities in pharmacokinetics after fentanyl drug delivery by the transdermal fentanyl patch delivery system in patients with cancer pain.

Neoadjuvant percutaneous 4-hydroxytamoxifen decreases breast tumoral cell proliferation: a prospective controlled randomized study comparing three doses of 4-hydroxytamoxifen gel to oral tamoxifen.

Purpose: Two chemoprevention randomized studies using tamoxifen showed drug efficacy; however, adverse effects such as hot flushes, endometrial cancer, and above all, thromboembolism, remain a problem. 4 hydroxytamoxifen (4-OHT) is a very active metabolite of tamoxifen. This randomized study was designed to analyze if 4-OHT gel, administered percutaneously on the breast skin, can inhibit the proliferation of malignant breast cells to the same extent as orally administered tamoxifen.

Population pharmacokinetics of melphalan, infused over a 24-hour period, in patients with advanced malignancies.

Purpose: The objective of the present study was to characterize the population pharmacokinetics of melphalan infused over a 24-h period in patients with advanced malignancies.

Methods: Enrolled in the study were 64 patients (144 courses). The population pharmacokinetic analysis was performed using NONMEM through the graphical interface Visual-NM.

Sensitive HPLC-fluorescence method for irinotecan and four major metabolites in human plasma and saliva: application to pharmacokinetic studies.

Background: We developed gradient HPLC methods for quantification of the antimitotic drug irinotecan (CPT-11) and its four metabolites, SN-38, SN-38 G, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin (APC), and 7-ethyl-10-[4amino-1-piperidino]-carbonyloxycamptothecin (NPC), as the sum of the lactone and carboxylate forms, in human plasma and saliva. Camptothecin was used as internal standard.

Methods: The sample pretreatment involved protein precipitation with methanol-acetonitrile (50:50 by volume) followed by acidification with hydrochloric acid to convert the lactone ring-opened form into its lactone form, quantitatively.

Modeling plasma and saliva topotecan concentration time course using a population approach.

The purpose of this study was to develop a pharmacokinetic model simultaneously accounting for topotecan concentrations in plasma and saliva. Thirteen patients with metastatic epithelial ovarian cancer received topotecan. During the first and the second courses of treatment, each patient underwent pharmacokinetic evaluation.

In vitro and in vivo pharmacological characterisation of the antitumour properties of pyrido[1',2':1,2]imidazo[4,5-h]quinazoline.

The anti-tumour activity of pyrido[1',2':1,2]imidazo[4,5-h]quinazoline (PIQ) was investigated in vitro and in vivo with a human tumour model. In vitro PIQ cytotoxicity was evaluated on two different human parental-sensitive cancer cell lines (HL60S and A2780S) and their multidrug-resistant variant sublines (HL60R and A2780R). Proliferation was assessed using the MTT assay and PIQ showed activity, particularly with resistant cell lines.