Therapeutic selection during an emergency response.

Therapeutic selection in a postdisaster setting is described. Therapeutic selection is the process of assessing a patient's pharmaceutical requirements and selecting the appropriate therapy. Although the primary criteria for drug selection during a disaster response are the same as in usual pharmacy practice, there is a shift in emphasis created by communication and transportation limitations and by changes in the patient's general living environment. The cost of agents is no longer viewed in terms of dollars but in the context of limited inventories. A disaster may exacerbate health problems or make adverse drug effects more common and problematic. Drug administration and patient compliance will be hampered. Pre-established guidelines for appropriate patient care should be reviewed and approved by a group of representative health care providers. General policies for pharmaceutical care should include guidelines for a formulary, prescription refills, dispensing limitations, and prescriber approval. Therapeutic selection should involve obtaining a medical history, selecting a drug regimen, educating and counseling the patient, and documenting the process. Pharmacists should use familiar procedures that they are comfortable with to minimize stress and optimize outcomes. Procedures should be flexible to adjust to circumstances and individual patient needs. Therapeutic selection during a disaster response, although based on the same principles as traditional therapeutic selection, is more complex. Pharmacists will need to tailor their approach to the circumstances and to individual patient needs.

Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine via the Group C protocol mechanism of the National Cancer Institute: a report of 979 patients.

PURPOSE: To provide cladribine (CdA) to physicians for the treatment of patients with previously treated or untreated hairy cell leukemia (HCL), and to determine the response rate, response duration, survival, and toxicity with this agent. PATIENTS AND METHODS: This Group C phase II study was open to all eligible patients whose primary physician obtained written permission from the National Cancer Institute (NCI) to register patients onto this protocol. Of 979 patients registered, 861 were assessable for response and 895 for toxicity. RESULTS: The complete remission (CR) rate was 50% and the partial remission (PR) rate was 37%. At a median follow-up of 52 months, 12% of patients were reported to have progressed and 62 (7%) have died of disease. CONCLUSION: This large experience confirms the excellent response rates and remission duration of CdA in patients with HCL. Nevertheless, the response rates in this setting, which approximates general clinical practice, were lower than in other series. In general, CdA was well tolerated, but the potential increased risk for secondary malignancies requires additional follow-up evaluation. CdA can now be considered as one of the best agents for the treatment of HCL.

Standardizing the expression and nomenclature of cancer treatment regimens. American Society of Health-System Pharmacist (ASHP), American Medical Association (AMA), American Nurses Association (ANA).

Guidelines for describing cancer chemotherapy regimens in all aspects of drug development, including treatment protocols, order forms, and product labels, are proposed. To complement the approaches to reducing medication errors that have been recommended by ASHP and others, pharmacists at the National Institutes of Health and the National Cancer Institute, with the input of oncology pharmacists from diverse areas of practice, developed guidelines for expressing chemotherapy dosage schedules and treatment regimens. The guidelines present standards that are broadly applicable and can be adopted by other institutions. Clear and unambiguous expression of all medication orders and consistency of treatment descriptions are suggested. Written treatment plans and orders should contain enough information to allow health care providers from diverse disciplines to compare them with published treatment descriptions and investigational protocols and must therefore include planned dosages and schedules expressed in patient-specific units. In general, drug dosages should be expressed as the amount of drug administered from a single container. When ordering drugs that are part of complex or combination-drug regimens, prescribers should write as many of the orders at one time as is possible, so that continuity might be preserved. Standard rules are proposed for describing chemotherapy regimens.

Carboxypeptidase-G2, thymidine, and leucovorin rescue in cancer patients with methotrexate-induced renal dysfunction.

PURPOSE: Methotrexate nephrotoxicity can lead to delayed methotrexate elimination and the development of life-threatening toxicity, which may not be preventable with the standard rescue agent leucovorin. In preclinical studies, we previously demonstrated that carboxypetidase-G2 (CPDG2) rapidly hydrolyzes methotrexate to nontoxic metabolites. A protocol for the compassionate use of CPDG2 in patients who develop nephrotoxicity while receiving high-dose methotrexate was therefore developed. The pharmacologic and clinical outcome of CPDG2 rescue administered with thymidine and leucovorin in 20 patients is presented here. METHODS: Patients with high-dose methotrexate-induced renal dysfunction received one to three doses of CPDG2, 50 U/kg body weight intravenously (i.v.), thymidine 8 g/m2/d by continuous i.v. infusion, and standard pharmacokinetically guided leucovorin rescue. Plasma concentrations of methotrexate and its inactive metabolite 4-deoxy-4-amino-N10-methylpteroic acid (DAMPA) were measured before and after CPDG2 using high-pressure liquid chromatography (HPLC). Tolerance of CPDG2 and thymidine, development of methotrexate toxicities, and recovery of renal function were monitored. RESULTS: Twenty patients who received high-dose methotrexate for osteosarcoma (n = 11), lymphoid cancers (n = 8), and gastric cancer (n = 1) developed nephrotoxicity (median serum creatinine, 3.2 mg/dL) and elevated plasma methotrexate concentrations (median, 201 mumol/L at hour 46). CPDG2 and thymidine rescue was well tolerated and resulted in a rapid 95.6% to 99.6% reduction in the plasma methotrexate concentration. Methotrexate-related toxicity was mild to moderate. Serum creatinine returned to normal values at a median of 22 days. CONCLUSION: CPDG2, thymidine, and leucovorin rescue was highly effective in 20 patients at high risk for developing life-threatening methotrexate toxicity after the onset of methotrexate-induced nephrotoxicity and delayed methotrexate excretion.

Cladribine for the treatment of hematologic malignancies.

The mechanism of action, pharmacokinetics, efficacy, adverse effects, storage, dosage and administration, and cost of cladribine are reviewed. Cladribine (2-chloro-2'-deoxyadenosine) is a synthetic purine nucleoside developed for the treatment of hematologic malignancies. It appears that cladribine interferes with lymphocyte proliferation by inhibiting DNA repair. The pharmacokinetics of cladribine best fit a two-compartment, first-order-elimination model. Of the conditions that have been treated with cladribine, hairy cell leukemia (HCL) has shown the most dramatic response. Overall response rates in clinical studies have ranged from 80% to 100%, with a large majority of these being complete remissions; median durations of responses have ranged from about 9 to 16 months. Other conditions that have responded to cladribine are chronic lymphocytic leukemia (CLL), acute leukemia, chronic myeloid leukemia, low-grade lymphomas, Waldenström's macroglobulinemia, and cutaneous T-cell lymphoma. The drug is inactive against solid tumors. The principal dose-limiting adverse effect of cladribine is bone marrow suppression; fever, immunosuppression, renal and neurologic effects, and local skin reactions have also been reported. The drug is typically administered as an extended continuous i.v. infusion. The usual dosage for treating HCL is 0.1 mg/kg/day for seven days. The estimated cost of cladribine for treating an average patient with HCL is $3500. Cladribine has shown efficacy against a variety of hematologic malignancies, notably HCL and CLL.