Palonosetron triggers 5-HT(3) receptor internalization and causes prolonged inhibition of receptor function.

Palonosetron is a 5-HT(3) receptor antagonist that has demonstrated superiority in preventing both acute and delayed emesis when compared to older first generation 5-HT(3) receptor antagonists. The objective of this work was to determine if palonosetron exhibits unique molecular interactions with the 5-HT(3) receptor that could provide a scientific rationale for observed clinical efficacy differences. Previously, we showed that palonosetron exhibits allosteric binding and positive cooperativity to the 5-HT(3) receptor in contrast to ondansetron and granisetron which exhibit simple bimolecular binding.

New approaches to chemotherapy-induced nausea and vomiting: from neuropharmacology to clinical investigations.

Nausea and vomiting are considered to be among the most distressing consequences of cytotoxic chemotherapies. Currently, there are several novel 5-HT(3) receptor antagonists for the treatment of chemotherapy-induced nausea and vomiting (CINV), including ondansetron, granisetron, and dolasetron. These agents provide significant improvement in the management of acute emesis but are ineffective at preventing delayed emesis.

Palonosetron: a unique 5-HT3 receptor antagonist indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting.

Despite the advance in supportive care that occurred with the introduction of selective serotonin subtype 3 (5-HT3) receptor antagonists, control of chemotherapy-induced nausea and vomiting (CINV) with first-generation agents (ondansetron, dolasetron, and granisetron) is less than ideal. Palonosetron is a unique 5-HT3 receptor antagonist whose distinctive pharmacologic characteristics (ie, high 5-HT3 receptor binding affinity, prolonged half-life) result in superior clinical benefit. Superiority of palonosetron over ondansetron and dolasetron in the prevention of both acute and delayed CINV has been observed in each phase III trial conducted.

Rankings and symptom assessments of side effects from chemotherapy: insights from experienced patients with ovarian cancer.

Goals Of Work: Although many patients with ovarian cancer achieve favorable responses to primary chemotherapy, the majority of women will experience recurrence of their cancer. Selection of second- or third-line chemotherapy ultimately depends on patient preferences for different side effects. To better understand this process, we evaluated preferences and symptom distress in patients with ovarian cancer.

Incidence of chemotherapy-induced nausea and emesis after modern antiemetics.

Background: The authors determined the incidence of acute and delayed chemotherapy-induced nausea and emesis (vomiting) (CINV) among patients receiving highly (HEC) or moderately (MEC) emetogenic chemotherapy. They also assessed whether physicians and nurses accurately recognized the incidence of acute and delayed CINV in their own practices.

Methods: A prospective, observational study of adult patients receiving HEC or MEC for the first time was performed.

Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis.

Background: Oral and gastrointestinal (GI) mucositis can affect up to 100% of patients undergoing high-dose chemotherapy and hematopoietic stem cell transplantation, 80% of patients with malignancies of the head and neck receiving radiotherapy, and a wide range of patients receiving chemotherapy. Alimentary track mucositis increases mortality and morbidity and contributes to rising health care costs. Consequently, the Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology assembled an expert panel to evaluate the literature and to create evidence-based guidelines for preventing, evaluating, and treating mucositis.

Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients.

Background: A frequent complication of anticancer treatment, oral and gastrointestinal (GI) mucositis, threatens the effectiveness of therapy because it leads to dose reductions, increases healthcare costs, and impairs patients' quality of life. The Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology assembled an international multidisciplinary panel of experts to create clinical practice guidelines for the prevention, evaluation, and treatment of mucositis.

Methods: The panelists examined medical literature published from January 1966 through May 2002, presented their findings at two separate conferences, and then created a writing committee that produced two articles: the current study and another that codifies the clinical implications of the panel's findings in practice guidelines.

Evidence-based guidelines for managing mucositis.

Objectives: To discuss implementation of evidence-based clinical practice guidelines for mucositis.

Data Source: Published articles, book chapters, web sources, clinical experience, unpublished manuscripts.

Conclusion: Nurses can implement evidence-based guidelines but must include an evaluation component to determine effect on clinical outcomes.

The burdens of cancer therapy. Clinical and economic outcomes of chemotherapy-induced mucositis.

Background: Mucositis is a common but poorly studied problem among patients with solid tumors. The authors examined the clinical and economic outcomes of oral and gastrointestinal (GI) mucositis among patients receiving myelosuppressive chemotherapy.

Methods: A retrospective, random sample of 599 patients who developed chemotherapy-induced myelosuppression was followed for development of oral or GI mucositis and for development of subsequent episodes of bleeding or infection.

Measuring chemotherapy-induced nausea and emesis.

Background: Chemotherapy-induced nausea and emesis (CINE) is one of the most dreaded side effects of cancer therapy. To investigate the influence of these symptoms on a patient's quality of life (QOL), a validated tool measuring many domains is needed.

Methods: A QOL questionnaire consisting of scales from the European Organization for Research and Treatment of Cancer QLQ-C30, the Morrow Assessment of Nausea and Emesis, the Osoba Nausea and Emesis Module, and new items specific to nausea, emesis, and retching was constructed and administered daily for 7-9 days to outpatients receiving emetogenic chemotherapy.

Pharmacoeconomic analysis of oprelvekin (recombinant human interleukin-11) for secondary prophylaxis of thrombocytopenia in solid tumor patients receiving chemotherapy.

Background: Previous research has shown oprelvekin (recombinant human interleukin-11 [rhIL-11]) to be effective in reducing the requirements for platelet transfusions after myelosuppressive chemotherapy in patients who have previously experienced thrombocytopenia. The economic consequences of the routine use of this platelet growth factor and the usual standard of platelet transfusions for prophylaxis of severe chemotherapy-induced thrombocytopenia have not been compared.

Methods: The authors constructed a decision-analytic model to compare the alternatives of rhIL-11 versus usual care using probability, outcome, and cost data from previously published clinical trials and their own institutional sources.

Patient preferences regarding side effects of chemotherapy for ovarian cancer: do they change over time?

Objective: The goals of this study were to: (1) systematically evaluate patient preferences regarding side effects of high-dose chemotherapy with stem cell support for treatment of advanced ovarian cancer; and (2) assess whether patients' preferences changed over time.

Methods: Forty patients with stage III or IV disease were enrolled in this study. Patients' preferences regarding 12 health states (side effects) were assessed using visual analogue scale (VAS) and time trade-off (TTO) methods during mobilization chemotherapy (T(1)) and 6-7 weeks later after high-dose chemotherapy and stem cell transplant (T(2)).

The Bleeding Risk Index: a clinical prediction rule to guide the prophylactic use of platelet transfusions in patients with lymphoma or solid tumors.

Background: The correlation between platelet count and bleeding has been well described, although no formal methods for applying this information to clinical decisions are available. The authors developed a clinical prediction rule to guide the prophylactic use of platelet transfusions among patients with lymphoma or solid tumors.

Methods: The Bleeding Risk Index (BRI) was developed from logistic regression analysis of a randomly selected 750-chemotherapy cycle derivation set using data from Day 1 of cycles.