palonosetron and Glioblastoma

Chemotherapy-induced nausea and vomiting (CINV) is a side effect related to administration of the adjuvant temozolomide (TMZ) in patients affected by glioblastoma. After chemoradiotherapy, adjuvant TMZ is administered as an oral multiple-day regimen, and TMZ-associated CINV may interfere with the continuation of chemotherapy, with potentially negative consequences on clinical efficacy. The aim of the present study was to investigate the efficacy of palonosetron for prevention of CINV-induced by adjuvant TMZ.. From March 2007 to August 2008, 33 patients with confirmed glioblastoma and eligible for adjuvant treatment with TMZ were enrolled in the study. All patients with responding or stable disease after concomitant radiotherapy plus daily TMZ (75 mg/m(2)) received a single i.v. bolus 0.25 mg of palonosetron 30 min before the beginning of adjuvant TMZ (150-200 mg/m(2)/day for five consecutive days every 4 weeks). The primary endpoint was the percentage of patients with complete response (CR), defined as no emetic episodes and no rescue medication during the overall phase (0-168 h). Secondary endpoints included CR during the 0-120 h and 0-168 h phases and complete control (CC; CR and no more than mild nausea) during the 0-120 h, 120-168 h, and 0-168 h phases.. Thirty-three patients were enrolled in the study (median age 57.6 years, 23 male and 10 female, median Karnofsky Performance Status = 80). Each patient was receiving fixed doses of dexamethasone (range 2-8 mg/day). CR in the 0-120 h, 120-168 h, and 0-168 h phases was seen in 91% of patients. CC was observed in 88%, 91%, and 88% of cases during the 0-120 h, 120-168 h, and 0-168 h phases, respectively. Anti-emetic prophylaxis with palonosetron was well tolerated and the most frequent adverse event was grade 1-2 headache reported by seven patients (21%).. A single dose of palonosetron before the initiation of multiple oral doses of TMZ, in patients on treatment with steady doses of dexamethasone, provides a high protection against CINV throughout the overall phase (0-168 h). The pharmacological profile of palonosetron, compared to first-generation 5-HT3 receptor antagonists, may have an impact on its clinical efficacy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents, Alkylating; Chemotherapy, Adjuvant; Combined Modality Therapy; Dacarbazine; Dexamethasone; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Glioblastoma; Humans; Isoquinolines; Male; Middle Aged; Nausea; Palonosetron; Quinuclidines; Serotonin Antagonists; Temozolomide; Vomiting

A quality improvement project was implemented to improve adherence to evidence-based antiemetic guidelines for malignant glioma patients treated with moderately emetic chemotherapy (MEC). Poorly controlled chemotherapy-induced nausea and vomiting (CINV) reduce cancer treatment efficacy and significantly impair cancer patients' quality of life (QOL). A review of Duke University Preston Robert Tisch Brain Tumor Center (PRTBTC)'s usual practice demonstrates a high incidence (45%) of CINV, despite premedication with short-acting 5-HT3-serotonin-receptor antagonists (5-HT3-RAs). National Comprehensive Cancer Network (NCCN)'s evidence-based guidelines recommend the combination of the long-acting 5-HT3-RA palonosetron (PAL) and dexamethasone (DEX) for the prevention of acute and delayed CINV with MEC. Low adherence (58%) to antiemetic guidelines may have explained our high CINV incidence.. One-sample binomial test, quasi-experimental design, evaluated a combination intervention that included a provider education session; implementation of risk-assessment tool with computerized, standardized antiemetic guideline order sets; and a monthly audit-feedback strategy. Post-implementation adherence to evidence-based antiemetic order sets and patient outcomes were measured and compared to baseline and historical data. Primary outcome was the guideline order set adherence rate. Secondary outcomes included nausea/vomiting rates and QOL.. Adherence to ordering MEC guideline antiemetics increased significantly, from 58% to a sustained 90%, with associated improvement in nausea/vomiting. In acute and delayed phases, 75 and 84% of patients, respectively, did not experience CINV. There was no significant change in QOL.. Combination intervention and audit-feedback strategy to translate evidence into oncology practice improved and sustained adherence to antiemetic guidelines. Adherence corresponded with effective nausea/vomiting control and preserved QOL in patients with malignant gliomas.

Topics: Adult; Antiemetics; Antineoplastic Agents; Brain Neoplasms; Dexamethasone; Female; Glioblastoma; Humans; Isoquinolines; Male; Medication Adherence; Middle Aged; Nausea; Neoplasms; Palonosetron; Quality of Life; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Translational Research, Biomedical; Treatment Outcome; Vomiting