Real-World Experience of Bevacizumab as First-Line Treatment for Ovarian Cancer: The GINECO ENCOURAGE Cohort of 468 French Patients.

Bevacizumab-containing therapy is considered a standard-of-care front-line option for stage IIIB-IV ovarian cancer based on results of randomized phase 3 trials. The multicenter non-interventional ENCOURAGE prospective cohort study assessed treatment administration and outcomes in the French real-world setting. Eligible patients were aged ≥ 18 years with planned bevacizumab-containing therapy for newly diagnosed ovarian cancer.

Single-arm phase II trial to evaluate efficacy and tolerance of regorafenib monotherapy in patients over 70 with previously treated metastatic colorectal adenocarcinoma FFCD 1404 - REGOLD.

Background: Regorafenib significantly increases overall survival (OS) in patients with metastatic colorectal cancer previously treated but gives toxicities.

Objectives: to assess the efficacy and safety of regorafenib at it's approved dose in the older population.

Patients And Methods: This multicenter single-arm phase II enrolled patients ≥70 years old after the failure of fluoropyrimidine-based chemotherapy, anti-VEGF, and anti-EGFR treatment.

Non-pegylated liposomal doxorubicin (NPLD, Myocet®) + carboplatin in patients with platinum sensitive ovarian cancers: A ARCAGY-GINECO phase IB-II trial.

Background: Carboplatin and pegylated liposomal doxorubicin combination is a standard regimen in platinum-sensitive recurrent ovarian cancer patients. The pegylated liposomal doxorubicin shortage from 2011 to 2013 urged assessment of the efficacy and tolerance of non-pegylated liposomal doxorubicin in combination with carboplatin.

Methods: MYCA was a multicenter 2-step phase Ib-II single arm trial meant to assess the safety and efficacy of carboplatin AUC 5 mg/min.

[Medico-economic benefits of subcutaneous formulations of trastuzumab and rituximab in day hospitalisation (SCuBA Study)].

Introduction: New pharmaceutical forms of trastuzumab and rituximab which can be administered by the subcutaneous route have been developed recently. For day hospitalisation units, these can be used in simpler treatment protocols than previous intravenous formulations. The objective of this study was to evaluate the medical and economic consequences of switching to subcutaneous formulations of trastuzumab and rituximab.

Dose intensity and toxicity associated with Taxotere formulation: a retrospective study in a population of breast cancer patients treated with docetaxel as an adjuvant or neoadjuvant chemotherapy.

Docetaxel is an antineoplastic drug from the taxane family that inhibits tubulin polymerization. Its brand name is Taxotere. In mid-2010, the formulation of Taxotere changed from a two-vial preparation needing a predilution (T2V) to a one-vial ready-to-use preparation (T1V).

Combining paclitaxel and lapatinib as second-line treatment for patients with metastatic transitional cell carcinoma: a case series.

Background: Current first-line cisplatin-based combination chemotherapy regimens provide interesting response rates but limited impact on survival for patients with metastatic transitional cell carcinoma of the urothelium. Such results leave a significant patient population in need of salvage therapy.

Patients And Methods: As the epidermal growth factor receptors 1 and 2 (EGFR and HER2) are frequently overexpressed in urothelial carcinoma, we explored the feasibility of a combination of paclitaxel (80 mg/m(2)/week) and lapatinib (1,500 mg orally daily) for six patients who were treated after failure of first-line platinum-based chemotherapy.

WITHDRAWN: Second or third additional chemotherapy drug for non-small cell lung cancer in patients with advanced disease.

Background: Randomized trials have demonstrated that adding a drug to a single-agent or to a two-agent regimen increased the tumor response rate in patients with advanced non-small cell lung cancer (NSCLC), although its impact on survival remains controversial.

Objectives: To evaluate the clinical benefit of adding a drug to a single-agent or two-agent chemotherapy regimen in terms of tumor response rate, survival, and toxicity in patients with advanced NSCLC.

Search Methods: There were no language restrictions.

Sunitinib in advanced pancreatic neuroendocrine tumors: latest evidence and clinical potential.

Based on preclinical data available in the RIP1-Tag2 transgenic mouse model, sunitinib is an inhibitor of angiogenesis in pancreatic neuroendocrine tumors blocking vascular endothelial growth factor receptors and platelet-derived growth factor receptors in endothelial cells and pericytes, respectively. Evidence of objective response in phase I trials justified the initiation of a large phase II/III program using sunitinib in patients with advanced/metastatic well-differentiated pancreatic neuroendocrine tumors. In the phase II study, sunitinib showed potent antitumor activity and a safe toxicity profile.

5-fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) as second-line chemotherapy in patients with metastatic pancreatic adenocarcinoma.

Background: To evaluate the efficacy and toxicity of irinotecan and oxaliplatin plus 5-fluorouracil (FU) and leucovorin (FOLFIRINOX) as second-line therapy in metastatic pancreatic adenocarcinoma (MPA).

Patients And Methods: We retrospectively analyzed the medical records of 27 patients with MPA treated with FOLFIRINOX as second-line therapy between January 2003 and November 2009 in our hospital. The recommended schedule was oxaliplatin 85 mg/m(2) on day 1 + irinotecan 180 mg/m(2) on day 1 + leucovorin 400 mg/m(2) on day 1 followed by FU 400 mg/m(2) as a bolus on day 1 and 2,400 mg/m(2) as 46-hour continuous infusion biweekly.

FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer.

Background: Data are lacking on the efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) as compared with gemcitabine as first-line therapy in patients with metastatic pancreatic cancer.

Methods: We randomly assigned 342 patients with an Eastern Cooperative Oncology Group performance status score of 0 or 1 (on a scale of 0 to 5, with higher scores indicating a greater severity of illness) to receive FOLFIRINOX (oxaliplatin, 85 mg per square meter of body-surface area; irinotecan, 180 mg per square meter; leucovorin, 400 mg per square meter; and fluorouracil, 400 mg per square meter given as a bolus followed by 2400 mg per square meter given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine at a dose of 1000 mg per square meter weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. Six months of chemotherapy were recommended in both groups in patients who had a response.

Predictive biomarkers for the activity of mammalian target of rapamycin (mTOR) inhibitors.

In the quest for personalized medicine, only a few biological parameters are routinely used to select patients prior to the initiation of anticancer targeted therapies, including mTOR inhibitors. Identifying biological factors that may predict efficacy or resistance to mTOR inhibitors represents an important challenge since rapalogs may exert antitumor effects through multiple mechanisms of action. Despite the fact that no such a factor is currently available, several molecular patterns are emerging, correlating with sensitivity and/or resistance to rapalogs.

Phase I evaluation of seliciclib (R-roscovitine), a novel oral cyclin-dependent kinase inhibitor, in patients with advanced malignancies.

Aim: Phase I study of seliciclib (CYC202, R-roscovitine), an inhibitor of cyclin-dependent kinases 2, 7 and 9, causing cell cycle changes and apoptosis in cancer cells.

Patients And Methods: This phase I trial aimed at defining the toxicity profile, the maximum tolerated dose (MTD), the recommended phase II dose (RD) and the main pharmacokinetic and pharmacodynamic parameters of oral seliciclib. Three schedules were evaluated: seliciclib given twice daily for 5 consecutive days every 3 weeks (schedule A), for 10 consecutive days followed by 2 weeks off (schedule B) and for 3d every 2 weeks (schedule C).

Benefits from pharmacological and pharmacokinetic properties of sunitinib for clinical development.

Importance Of The Field: In the last 10 years, oncology has been greatly modified by the introduction of new drugs especially designed for molecular targets. Sunitinib belongs to the category of new drugs that inhibit multityrosine kinase receptors involved in the key steps of tumorigenesis and angiogenesis.

Areas Covered In This Review: This article reviews the pharmacological and clinical aspects of sunitinib.

[Management of biliary tract carcinomas].

Biliary tract carcinomas are rare tumours, counting for less than 5% of cancer. Biliary tract carcinomas comprise gallbladder carcinoma and cholangiocarcinoma, which arise from the intrahepatic or extrahepatic bile ducts. These tumours have a poor prognosis, with a median survival of 6 months for advanced disease.

Population pharmacokinetics and pharmacogenetics of imatinib in children and adults.

Purpose: The aim of this study was to explore the effect of several demographic, biological, and pharmacogenetic covariates on the disposition of imatinib and its main metabolite (CGP74588) in both adults and children.

Experimental Design: Thirty-three children with solid malignancies included in a phase II exploratory study and 34 adults with gastrointestinal stromal tumors received 340 mg/m(2) and 400 mg imatinib, respectively. Plasma imatinib and CGP74588 concentrations observed on day 1 and at steady-state were analyzed by a population pharmacokinetic method (NONMEM) to evaluate the effect of age, body weight, age, sex, albuminemia, plasma alpha1-acid glycoprotein (AGP), and eight polymorphisms corresponding to ABCB1, ABCG2, CYP3A4, CYP3A5, and AGP (pharmacogenetic data available for 46 of 67 patients).

Safety of repeated administrations of ixabepilone given as a 3-hour infusion every other week in combination with irinotecan in patients with advanced malignancies.

Epothilones are active tubulin-interacting agents that warrant combinations in clinical studies. This phase I combination study explored ixabepilone administered as a 3-h infusion followed by a 90-minute infusion irinotecan, on days 1 and 14 of every 28-day cycle. Forty-one patients received doses of ixabepilone and irinotecan ranging from 15-30 mg/m(2) and 120-180 mg/m(2) every 2 weeks for a total of 173 cycles, respectively.

Second or third additional chemotherapy drug for non-small cell lung cancer in patients with advanced disease.

Background: Randomized trials have demonstrated that adding a drug to a single-agent or to a two-agent regimen increased the tumor response rate in patients with advanced non-small cell lung cancer (NSCLC), although its impact on survival remains controversial.

Objectives: To evaluate the clinical benefit of adding a drug to a single-agent or two-agent chemotherapy regimen in terms of tumor response rate, survival, and toxicity in patients with advanced NSCLC.

Search Strategy: There were no language restrictions.

Phase I and pharmacokinetic study of etaracizumab (Abegrin), a humanized monoclonal antibody against alphavbeta3 integrin receptor, in patients with advanced solid tumors.

This study assessed the safety, immunogenicity, and pharmacokinetics of etaracizumab, a monoclonal antibody directed against the alphavbeta3 integrin, in patients with advanced malignancies. Four cohorts of four patients received escalating dose of etaracizumab as a 30-min intravenous infusion, first as a single test dose, followed-up 2-5 weeks later by weekly doses. Sixteen patients with advanced solid tumors received a total of 309 cycles of etaracizumab at doses ranging 1-6 mg/kg.

Stents for palliation of obstructive metastatic colon cancer: impact on management and chemotherapy administration.

Hypothesis: The more rapid and less complicated recovery after palliative stent insertion compared with surgery may theoretically facilitate the early administration of chemotherapy.

Design: A retrospective study.

Setting: University tertiary care referral center.

Phase II clinical trial of the epothilone B analog, ixabepilone, in patients with non small-cell lung cancer whose tumors have failed first-line platinum-based chemotherapy.

Purpose: Ixabepilone is the first in a new class of antineoplastic agents, the epothilones and their analogs. This international, randomized, phase II trial assessed two administration schedules of ixabepilone as second-line therapy in patients with non-small-cell lung cancer (NSCLC).

Patients And Methods: Patients had experienced disease progression after one prior cisplatin- or carboplatin-based chemotherapy regimen.

[Pharmacokinetic-pharmacodynamics relationships of imatinib (Glivec)].

Imatinib (Glivec) is a specific inhibitor of tyrosine kinase receptor, in particular of the proto-oncogene c-kit. Proto-oncogene c-kit is expressed or mutated in stromal digestive tumors (GIST). Pharmacokinetic (PK) analysis showed that imatinib displayed linear PK in patients with advanced GIST.

Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group.

Purpose: Imatinib is the standard treatment of advanced GI stromal tumors (GISTs). It is not known whether imatinib may be stopped in patients in whom disease is controlled.

Methods: This prospective, randomized, multicentric phase III study was designed to compare continuous (CONT) compared with interrupted (INT) imatinib beyond 1 year of treatment in patients with advanced GIST.

Pharmacokinetic-pharmacodynamic relationships of imatinib and its main metabolite in patients with advanced gastrointestinal stromal tumors.

Purpose: This study explored factors affecting the pharmacokinetic variability of imatinib and CGP 74588, and the pharmacokinetic-pharmacodynamic correlations in patients with advanced gastrointestinal stromal tumors.

Experimental Design: Thirty-five patients with advanced gastrointestinal stromal tumors received 400 mg of imatinib daily. Six blood samples were drawn: before intake, during 1- to 3- and 6- to 9-hour intervals after intake on day 1, and before intake on days 2, 30, and 60.

Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer.

Purpose: To establish the safety, pharmacokinetics, and recommended dose of sunitinib, a novel oral multitargeting tyrosine kinase inhibitor with antiangiogenic and antitumor properties, in patients with advanced malignancies.

Patients And Methods: Sunitinib was given orally for 4 weeks every 6 weeks.

Results: Twenty-eight patients received doses ranging from 15 to 59 mg/m2 (ranging from 50 mg every other day to 150 mg/d).

Phase I and pharmacokinetic study of aplidine, a new marine cyclodepsipeptide in patients with advanced malignancies.

Purpose: To establish the safety, pharmacokinetic parameters, maximum-tolerated dose, and recommended dose of aplidine, a novel marine cyclodepsipeptide, in patients with advanced cancer.

Patients And Methods: Using a modified Fibonacci method, we performed a phase I and pharmacokinetic study of aplidine administered as a 24-hour intravenous infusion every 2 weeks.

Results: Sixty-seven patients received aplidine at a dose ranging from 0.