Ann M. Hesketh

Dose-ranging evaluation of the antiemetic efficacy of intravenous dolasetron in patients receiving chemotherapy with doxorubicin or cyclophosphamide

Selective 5-HT3 antagonists have proven to be safe and effective for the prevention of chemotherapy-induced nausea and vomiting. Dolasetron is a new highly selective addition to this class of antiemetics that has been shown to have significant antiemetic activity in patients receiving cisplatin-containing regimens. This pilot study was designed to evaluate the antiemetic efficacy of dolasetron in cancer patients receiving doxorubicin and/or cyclophosphamide. This study used an openlabel, non-randomized design to evaluate the efficacy and safety of intravenous dolasetron in the prevention of emesis in patients receiving doxorubicin (25–75 mg/m2) and/or cyclophosphamide (400–1200 mg/m2). Sixty-nine patients received a single, intravenous dose of dolasetron over 15–20 min beginning 30 min prior to the start of chemotherapy. Dose levels of dolasetron studied were: 0.3, 0.6, 1.2, 1.8 and 2.4 mg/kg. Patients were monitored for emesis, nausea and adverse events for 24 h after the start of chemotherapy. Overall, 61% of patients experienced complete control of emesis. No significant trend towards increased antiemetic efficacy (P = 0.076) or nausea control with increasing dolasetron dose was noted, although the power to detect significant differences was limited by the small number of patients on the 0.3-mg/kg and 2.4-mg/kg dose levels. Age, gender, and type of chemotherapy were significant predictors of complete antiemetic control. Adverse events were generally mild and included headache, chills, light-headedness, fever, diarrhea, dizziness, and asymptomatic prolongation of ECG intervals. Intravenous dolasetron is safe and effective in the prevention of emesis induced by doxorubicin and/or cyclophosphamide.

Prospective evaluation of antiemetic outcome following high-dose chemotherapy with hematopoietic stem cell support

Considerable progress has been made in improving the control of chemotherapy-induced emesis. The impact of available antiemetic options for patients receiving stem cell transplants is unclear, as few prospective data have been collected. We prospectively evaluated antiemetic outcome in patients receiving stem cell transplantation over a 7-day period following the initiation of chemotherapy. The primary endpoints were the number of emetic episodes and the extent of nausea measured on a four-point scale. Eighty-two patients were evaluated. Ninety-five percent of patients had nausea during the first week of treatment; 80% had at least one emetic episode. The percentage of patients with emesis was as follows: day 1: 13%, day 2: 21%, day 3: 30%, day 4: 38%, day 5: 44%, day 6: 39%, day 7: 18%. In multivariate analysis, gender, emesis with prior chemotherapy, history of morning or motion sickness, type of transplant (auto vs allo), use of total body irradiation, or use of dexamethasone did not effect emesis control. Most patients receiving high-dose chemotherapy experience incompletely controlled emesis. Control of nausea and emesis progressively worsened with each subsequent day following initiation of chemotherapy, reaching a nadir on day 5. New treatment approaches are needed to improve emesis control in this patient population.Bone Marrow Transplantation (2001) 28, 1061–1066.

Control of high-dose-cisplatin-induced emesis with an all-oral three-drug antiemetic regimen

Abstract In this pilot trial, the antiemetic efficacy and tolerability of an all-oral antiemetic combination in the prevention of both acute and delayed nausea and vomiting following high-dose cisplatin was evaluated. Fifty-two patients receiving cisplatin (median dose 100 mg/m2) were entered. Patients received (1) 60 min prior to cisplatin: prochlorperazine spansule 15 mg, dexamethasone 20 mg, granisetron 2 mg; (2) 12 h after cisplatin: prochlorperazine spansule 15 mg, dexamethasone 10 mg; (3) on days 2 and 3: prochlorperazine spansule 15 mg b.i.d., dexamethasone 8 mg b.i.d.; (4) on days 4 and 5: dexamethasone 4 mg b.i.d. All antiemetics were administered orally. The study period was the 120 h after cisplatin administration. The primary efficacy end-point was complete control (no vomiting, retching or antiemetic rescue) of delayed emesis (24–120 h after cisplatin). Complete control of delayed emesis was achieved in 26 patients (53%). Nineteen patients (39%) noted no delayed nausea. Complete control of acute emesis (24 h after cisplatin) was attained in 44 patients (86%). The no nausea rate during the first 24 h was 74%. Overall, 39 patients (80%) were satisfied or very satisfied with their outcome. Treatment was well tolerated with infrequent and minor adverse events. In conclusion, an all-oral combination of granisetron, dexamethasone and prochlorperazine is a highly effective and well-tolerated regimen for preventing acute cisplatin-induced emesis. Control of delayed emesis was not better than with current standard treatment, and more effective approaches are needed.

Treatment of advanced non-small cell lung cancer with very high-dose cisplatin combined with etoposide and mitomycin C

Background. Treatment options for advanced non‐small‐cell lung cancer are inadequate. There remains a critical need for more effective systemic therapies.