Maintenance Treatment Of Adult Patients Research Articles

Niraparib: First Global Approval.

Oral niraparib, a highly-selective, potent poly(ADP-ribose) polymerase (PARP)-1 and PARP-2 inhibitor, is approved in the USA for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. It is also under regulatory review in the EU for use in maintenance treatment in patients with platinum-sensitive, recurrent epithelial ovarian cancer who are in response to platinum-based chemotherapy. In the multinational, phase 3 NOVA trial in adult patients with platinum-sensitive, recurrent ovarian cancer, niraparib significantly prolonged median progression-free survival, irrespective of the presence or absence of a germline BRCA (gBRCA) mutation and irrespective of the presence or absence of homologous recombinant deficiency. Niraparib is also in development for use in other solid tumours, including breast and prostate cancer. This article summarizes the milestones in the development of niraparib leading to its first global approval for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer.

ISY-5-2 - HBOC management in PARP inhibitor development: Japanese perspective

BRCA1 and BRCA2 mutations are responsible genes which give an autosomal-dominant inherited trait predisposing women to both breast cancer (BC) and ovarian cancer (OC). We call the BRCA deficient disease group as hereditary BC and OC (HBOC). Poly (ADP-ribose) polymerase (PARP) is one of the enzymes which involved in DNA-damage repair. PARP inhibition produce synthetic lethal in BRCA1/2 mutated tumors with defective DNA repair via homologous recombination. Phase I and II clinical trials show that PARP inhibitors have shown promising activity in patients with HBOC patients. Olaparib, an oral, small molecule, PARP inhibitor, has recently been the approved for ovarian cancer therapy by the FDA and EMA. An Indication is maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete response or partial response to platinum-based chemotherapy. Phase III trial of olaparib vs. placebo in patients with the similar population with standard first line treatment, combining with platinum-Taxane chemotherapy and bevacizumab has just started (PAOLA). For BRCA-mutated breast cancer, phase III trials are ongoing in the adjuvant (OlympiA) and metastatic settings (OlympiAD). Some triple negative breast cancer (TNBC) has similar biological characteristics with HBOC, including high grade, p53 mutation, EGFR or cytokeratin 5/6 positive, chemo-sensitivity. Combination phase I/II study of olaparib with eribulin mesylate, a novel microtubule, for advanced TNBC has been conducted as investigator initiated trial in Japan. Currently, multiple PARPis are in various stages of clinical development, including in combination with other treatment modalities such as radiation, molecular targeted agents, and cytotoxic chemotherapies. In this session, I am going to focus the future strategy of the PARP inhibitors and clinical management of HBOC.

Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer.

Olaparib (Lynparza™) is a first-in-class, orally-active, small molecule, poly (ADP-ribose) polymerase inhibitor that induces synthetic lethality in homozygous BRCA-deficient cells. In the EU, the capsule formulation of olaparib is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive, relapsed, BRCA-mutated (germline and/or somatic), high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. This approval was based on the results of study 19, a randomized phase II trial in 265 patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer (HGSOC) who had received two or more platinum-based regimens and who had a partial or complete response to their most recent platinum-based regimen. Study 19 met its primary endpoint by demonstrating a significant improvement in progression-free survival in patients receiving olaparib compared with those receiving placebo. Moreover, a preplanned retrospective analysis identified those patients with a BRCA mutation (who comprised one-half of the overall study population) as being the subgroup that derived the greatest clinical benefit from olaparib. Single-agent olaparib was generally well tolerated, with the majority of adverse events being of mild to moderate severity and not requiring interruption of treatment. Fatigue, anaemia and neutropenia were the most frequently reported severe (grade ≥3) adverse events. An as yet unapproved tablet formulation of olaparib that has a lower pill burden than the capsule formulation is currently being investigated in phase III clinical studies.

Industry Update: the Latest Developments in Therapeutic Delivery

This update covers the period March 2013, with information sourced from company press releases, regulatory and patent agencies. This month saw approvals for therapeutics featuring drug-delivery technologies: Biogen Idec’s first-line oral multiple sclerosis drug Tecfidera™ and Novartis’ TOBI Podhaler™ for cystic fibrosis. Titan Pharmaceutical received positive news from the US FDA advisory board regarding its product for the maintenance treatment of adult patients with opioid dependence, Probuphine®. On the merger and acquisitions front, AstraZeneca paid a staggering US$240 million upfront to gain access to Moderna’s early-stage mRNA technology. Shire acquired Swedish company Premacure allowing it access to the neonatal therapeutic area.

Prevalencia y factores asociados a la no adherencia en el tratamiento farmacológico de mantenimiento en adultos con trastorno afectivo bipolar

IntroductionThis study aims to determine the prevalence and factors associated with non-adherence in maintenance treatment of adult patients diagnosed with bipolar disorder. MethodsCross sectional study with 124 patients. Adherence to treatment was evaluated by the Morisky-Green Test. A structured questionnaire was applied. It included variables associated with demographics factors and factors related to the patient, illness, treatment, family, therapeutic relationship, and health system. The Global Impression Scale Modified for Bipolar Disorder (CGI-BPM) and Family Apgar were used as well. ResultsThe prevalence of non-adherence to maintenance drug treatment was 29.8%. It was greater in women (64.9%) than men (35.1%), although this difference was not statistically significant (p = 0.17). The factors statistically significant associated with non-adherence factors were: Increased severity of the disease (OR 1.9), history of non-adherence (39% P=0,001), negative perception of the psychiatrist (100%, P=0.001), less insight (87%, RP4.65), greater stigma (50%, RP 6.2), having no family member to remind taking the drug (73%, P=0.001). ConclusionsThe prevalence was inside the range found in other studies. The statistically significant factors associated with non-adherence were: Severity of disease, history of non-compliance, stigma, no family support, poor insight, smoking habit, and negative perception of the psychiatrist.

Profile of olanzapine long-acting injection for the maintenance treatment of adult patients with schizophrenia

Olanzapine long-acting injection (OLAI) is a crystalline salt composed of olanzapine and pamoic acid, which permits a depot intramuscular formulation of olanzapine. The half-life of olanzapine pamoate is 30 days, and its steady state is reached approximately at 12 weeks. Oral supplementation of olanzapine is not required during OLAI initiation, according to Eli Lilly recommendations, although a study indicated that ≥60% of D2 receptor occupancy was reached only by the fifth injection cycle. To date, a short-term, placebo-controlled study of 8 weeks in acutely ill patients and a long-term, controlled trial of 24 weeks in stabilized patients have been conducted. In both the studies, efficacy and safety were similar to those of oral olanzapine, with the exception of an acute adverse effect, the so-called inadvertent intravascular injection event, which occurred 1–3 hours after the injection with an incidence rate of 0.07% per injection. It consisted of symptoms that are similar to those reported in cases of oral olanzapine overdose. The most significant studies published to date, on the use of olanzapine pamoate in schizophrenia, are reviewed in this article. The pharmacodynamic and pharmacokinetic profile and related side effects of OLAI are reported.