The efficacy and safety of once-daily Kytril (granisetron hydrochloride) tablets in the prophylaxis of nausea and emesis following fractionated upper abdominal radiotherapy.

This multicenter, randomized, double-blind study compared the efficacy and safety of once-daily oral granisetron 2 mg (n = 134) and placebo (n = 126) as prophylaxis for nausea and emesis in patients receiving upper abdominal fractionated radiotherapy. Patients were scheduled to receive 10-30 fractions of radiotherapy; granisetron (two 1-mg tablets) or placebo was administered 1 hr before radiotherapy on each scheduled treatment day. Treatment comparisons were made at 24 hr and at 10 and 20 fractions. Patients treated with granisetron experienced greater emetic control than those treated with placebo as evidenced by median times to first emesis (35 vs. 9 days, p < 0.001) and first nausea (11 vs. 1 day, p < 0.001). Overall endpoint analysis showed that proportionally more granisetron than placebo patients were emesis free (57.5% vs. 42.1%, p = 0.0047) and nausea free (30.6% vs. 16.7%, p = 0.0042). Furthermore, 25% more granisetron-treated than placebo-treated patients were emesis free and 20% more were nausea free on at least 80% of study treatment days. The most commonly reported adverse experiences in granisetron-treated patients were diarrhea, asthenia, and constipation. These findings demonstrate that a once-daily, 2-mg dose of oral granisetron is well tolerated and significantly more effective than placebo in preventing nausea and emesis induced by fractionated radiotherapy to the upper abdomen.

Oral granisetron for the prevention of acute late onset nausea and vomiting in patients treated with moderately emetogenic chemotherapy.

PURPOSE: To demonstrate the efficacy of oral granisetron 1 mg twice daily for the prevention of late onset nausea and vomiting after moderately emetogenic chemotherapy that includes cyclophosphamide, carboplatin, or doxorubicin. METHODS: Prior to chemotherapy, patients were stratified by gender and randomized to receive oral granisetron (1 mg tablet twice daily) or prochlorperazine (10 mg sustained release capsule twice daily). Study agents were administered 1 h prior to and 12 h after chemotherapy. Antiemetics were administered for seven consecutive days. Efficacy variables were assessed 48 and 72 h after administration of chemotherapy, and included no emesis, no nausea, no moderate or severe nausea, and no antiemetic rescue. Safety analysis included all patients who received medication. RESULTS: A total of 230 patients were included in the intent-to-treat analysis; 119 patients received granisetron and 111 patients received prochlorperazine. Females, and all patients combined, who received granisetron had significantly higher no-emesis rates at 48 h (p =.010 and p =.016, respectively) than patients who received prochlorperazine. No-nausea rates at 48 h were numerically higher for all patients combined and females who received granisetron rather than prochlorperazine. Response rates for no nausea or mild nausea were also numerically higher in females treated with granisetron, compared to prochlorperazine, at 48 h. Significantly more patients (p <.001) and females (p <.001) in the granisetron group than in the prochlorperazine group did not require rescue antiemetics at 48 h. At 72 h, efficacy results were comparable for granisetron and prochlorperazine. CONCLUSION: Oral granisetron is well tolerated and more effective than prochlorperazine in preventing nausea and vomiting for up to 48 h following treatment with moderately emetogenic chemotherapy.

Comparable safety and antiemetic efficacy of a brief (30-second bolus) intravenous granisetron infusion and a standard (15-minute) intravenous ondansetron infusion in breast cancer patients receiving moderately emetogenic chemotherapy.

PURPOSE: For patients receiving chemotherapy, optimization of antiemetic therapy in terms of safety of administration, efficacy, cost, and convenience remains a subject of intense clinical research. In this study, we evaluated and compared the safety and antiemetic efficacy of a single 30-second intravenous bolus infusion of granisetron which those of a standard 15-minute intravenous infusion of ondansetron in chemotherapy-naive breast cancer patients receiving moderately emetogenic chemotherapy. PATIENTS AND MATERIALS: This was a randomized, double-blind, double-dummy, multicenter crossover study of 623 chemotherapy-naive patients (two male, 621 female) receiving moderately emetogenic chemotherapy (cyclophosphamide plus doxorubicin, with or without 5-fluorouracil) for breast cancer. Patients were assigned randomly to receive either granisetron or ondansetron in cycle 1 and the other agent in cycle 2. Granisetron (10 micrograms/kg) was administered as a 30-second intravenous bolus infusion within 5 minutes before the start of chemotherapy, and ondansetron (32 mg) was administered as a 15-minute intravenous infusion beginning 30 minutes before the start of chemotherapy. A total of 573 patients received the two planned chemotherapy cycles. Safety assessment was based on the type and frequency of adverse experiences reported by the patient at 24 and 48 hours after chemotherapy began. Efficacy assessments included the occurrence of nausea or emesis and the proportion of patients who achieved total emetic control at 24 and 48 hours after chemotherapy. RESULTS: Similar proportions of patients in both treatment groups remained free of emesis at the 24-hour assessment period (58.6% and 62.7% of granisetron- and ondansetron-treated patients, respectively) and at 48 hours (42.2% and 45.0% for granisetron vs ondansetron) in both cycles. The proportions of granisetron- and ondansetron-treated patients who remained nausea-free for the first 24 hours after treatment in both cycles were 44.0% and 48.5%, respectively, and at 48 hours were 26.7% and 31.0%, respectively. Statistical analysis demonstrated no significant treatment-by-cycle interaction. The 30-second granisetron infusion and the 15-minute ondansetron infusion were well tolerated. However, administration of ondansetron as a 15-minute intravenous infusion produced abnormal vision (6.28%) in significantly more patients than granisetron (0.35%). DISCUSSION: These two intravenous 5-hydroxytryptamine3-receptor antagonist antiemetics were similarly effective in controlling acute nausea and emesis during two cycles of moderately emetogenic chemotherapy. Granisetron (30 seconds) and the longer infusion of ondansetron (15 minutes) were well tolerated; however, ondansetron was associated with a greater proportion of patients reporting abnormal vision. Granisetron administered as a 30-second bolus infusion allows a considerably shorter waiting time between the end of the antiemetic infusion and the initiation of chemotherapy. This shorter administration time may enhance patient convenience and provider efficiency.

A double-blind comparison of the efficacy of two dose regimens of oral granisetron in preventing acute emesis in patients receiving moderately emetogenic chemotherapy.

BACKGROUND: The purpose of this study was to define an optimal administration schedule of granisetron for patients receiving moderately emetogenic chemotherapy by comparing the antiemetic efficacy and safety of 2 mg of the drug administrated orally. METHODS: In this double-blind, randomized, parallel study, 2-dose regimens of oral granisetron were evaluated in 697 adult cancer patients. Patients were stratified by gender and randomized to receive 2 mg oral granisetron, either as a divided dose given 1 hour prior to chemotherapy and 12 hours after the start of chemotherapy, or as a single dose 1 hour prior to chemotherapy at Cycle 1. The primary efficacy endpoints assessed were the percentage of patients with complete response (no nausea, no emesis, and no additional antiemetic medication during the 24-hour post-chemotherapy interval) and the incidence of emesis and nausea. Following completion of Cycle 1, patients were given the opportunity to receive open-label granisetron (2 mg once daily) on the first day of each remaining cycle of chemotherapy. RESULTS: No statistically significant differences in any of the endpoints were observed between the two treatment groups. Approximately 50% of patients in both treatment groups achieved complete response. The proportion of patients with no episodes of emesis occurred with similar frequency in the two treatment groups. Approximately 52% of patients in either treatment group were free of nausea during the postchemotherapy period. There was no difference between treatment groups regarding the use of antiemetic rescue medication. Finally, the incidence of adverse experiences was similar for both treatment groups. CONCLUSIONS: Both dose regimens of oral granisetron were similarly effective in controlling nausea and vomiting in the 24-hour interval following chemotherapy. Granisetron was well tolerated with few adverse events attributable to the study drug.

Preparation and characterization of a pentaammineruthenium(III) derivative of horse heart ferricytochrome c.

A stable complex between pentaammineruthenium(III) and histidine-33 in horse heart ferricytochrome c is formed in the reaction between aquopentaammineruthenium(II) and the protein at pH 7. HPLC of the tryptic hydrolysate of the modified protein was employed to identify the pentaammineruthenium binding site. Spectroscopic measurements show that the integrity of the native structure in the vicinity of the heme c group is maintained in the ruthenium-modified protein. The reduction potentials are: heme c (Fe3+/2+), 0.26 V; Ru(NH3)5(His-33)3+/2+, 0.15 V (vs. normal hydrogen electrode).

Three-dimensional structure of pinwheel inclusions as determined by analytic geometry.

The three-dimensional ultrastructure of pinwheel inclusions found in two plant virus-host systems was determined by computer-assisted analytic geometry. Data obtained from electron micrographs of serially sectioned pinwheel inclusions were used to generate mathematical equations. The three-dimensional models described by the equations indicated that some pinwheels assume the hourglass shapes of elliptic hyperboloids. Electron micrographs obtained from thick sections of pinwheel inclusions tilted at various angles supported the elliptic hyperboloid models described by the mathematical equations.