Assuring the optimal use of serotonin antagonist antiemetics: the process for development and implementation of institutional antiemetic guidelines at Memorial Sloan-Kettering Cancer Center.

PURPOSE: The need to foster the appropriate and cost-effective use of serotonin-antagonist antiemetic drugs spurred the creation of guidelines. The process by which institution-wide guidelines at Sloan-Kettering were developed, implemented, assessed, and modified is described. METHODS: A multidisciplinary group working with disease-specific management teams assigned the emetic potential of chemotherapy programs to one of five categories. Antiemetic regimens, including a specified dose and schedule of a serotonin-antagonist and dexamethasone, were assigned to each emetic category. The information was collated by disease site and chemotherapy program into hospital-wide antiemetic regimen recommendations. Quality assessment was conducted initially and repeated each time the guidelines were modified. RESULTS: Patient surveys demonstrated a high level of satisfaction with emetic control, which was similar to reported results. Data from the latest survey showed zero emetic episodes in 93% and 87% of participants given moderate and highly emetogenic chemotherapy, respectively. Compliance with the guidelines, initially in 73%, has been improved using a standardized chemotherapy order "check box" labeled, "Antiemetics as per Guidelines." Antiemetic drug expenditures decreased from a projected $2.8 million to $1.3 million annually. CONCLUSION: The guidelines became an educational tool that ensured the delivery of optimal antiemetic therapy chosen by professionals with the greatest knowledge of both the particular chemotherapy regimen and cancer site. Implementation of the guidelines resulted in substantial savings while treating more patients. The guidelines were easily modified as new chemotherapeutic agents and antiemetic drugs became available.

Continuous infusion fluorouracil/leucovorin and bolus mitomycin-C as a salvage regimen for patients with advanced colorectal cancer.

BACKGROUND: No effective systemic salvage therapy exists for patients with advanced colorectal cancer who progress after receiving bolus fluorouracil (FU) and leucovorin (LV) chemotherapy. In vitro data suggest that bolus FU resistance can be overcome by continuous infusion (CI) FU, and that the cytotoxic effects of Mitomycin-C (MMC) and FU are synergistic. Based on this data, a Phase II trial of CI FU and LV with bolus MMC in patients with advanced colorectal carcinoma who progressed on only one previous chemotherapy regimen was performed. METHODS: Twenty-eight patients with advanced colorectal carcinoma who had progressed after one previous chemotherapy regimen of bolus FU/LV were treated with bolus MMC 10 mg/m2 every 6 weeks and CI FU 200 mg/m2/day admixed with LV 10 mg/m2/day given 14 days on/7 days off. RESULTS: The partial response rate in 24 evaluable patients was 17% (95% confidence interval, 2-32%) with a median response duration of 9.5 months (range, 4.2-12.0 months). Twelve (50%) additional patients achieved disease stabilization. Median survival was 9.9 months in the whole group (28 patients) and 11.5 months in the 24 evaluable patients. The major toxicities were grade 4 diarrhea occurring in two patients and grade 3 mucositis occurring in five patients. There was minimal myelosuppression (grade 3 thrombocytopenia in one patient) and no occurrences of hand-foot syndrome or cardiotoxicity. CONCLUSIONS: This regimen demonstrates modest activity with acceptable toxicity in colorectal cancer patients who have failed a single-bolus FU/LV regimen. Modifications of this and other infusional FU-based chemotherapy regimens should be explored as potential salvage chemotherapy regimens in advanced colorectal cancer.

Systemic absorption of a leucovorin mouth wash: a pharmacologic study.

Mucositis is one of the major problems encountered after the administration of systemic chemotherapy. Leucovorin, routinely used as a rescue agent for methotrexate may reduce toxicity, but may also reduce the effectiveness of the chemotherapeutic agent. If leucovorin is administered as a mouth wash, local toxicity may be reduced without loss of methotrexate efficacy. In order to study this, 15 normal human volunteers were given leucovorin mouth wash and then had plasma determinations of 5-methyl-tetrahydrofolate and citrovorum factor. Small but statistically significant increases in plasma levels of 5-methyl-tetrahydrofolate were observed with no increase in levels of plasma citrovorum factor. It is concluded therefore that a small amount of leucovorin is absorbed systemically when administered as a mouth wash, but such an amount would most likely not be significant enough to reduce the effect of methotrexate therapy, but may reduce mucositis.

Stability of refrigerated and frozen solutions of doxorubicin hydrochloride.

The stability of refrigerated and frozen solutions of doxorubicin hydrochloride was studied. Vials of doxorubicin hydrochloride with lactose (Adriamycin) were reconstituted with Sterile Water for Injection, USP, to provide a drug concentration of 2 mg/ml. Samples were refrigerated (4 C) for up to one year and frozen (-20C) for 30 days then assayed by high-performance liquid chromatography. One sample was assayed then refrozen each test period. Refrigerated and frozen samples showed no substantial loss of potency after six months and one month of storage, respectively. Filtration through a 0.22-micron filter did not affect potency. Degradation products were not detected, except for an unidentified small peak detected in the sample refrigerated for one year. Doxorubicin hydrochloride, when reconstituted with sterile water for injection, may be refrigerated for six months or frozen for one month without loss of potency.