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.

Treatment of refractory chronic lymphocytic leukemia with fludarabine phosphate via the group C protocol mechanism of the National Cancer Institute: five-year follow-up report.

PURPOSE: To provide fludarabine to physicians for the management of patients with advanced refractory chronic lymphocytic leukemia (CLL) and to determine the response rate and duration, toxicity, and survival with this agent. PATIENTS AND METHODS: This phase II protocol was open to all eligible patients whose local physicians obtained written permission from the National Cancer Institute (NCI) to register patients onto this protocol. Of 791 national and international enrolled patients, 724 with a median age of 65 years received fludarabine, of which 703 were assessable for response. RESULTS: Thirty-two percent of assessable patients responded (95% confidence interval [CI], 29% to 36%), with 21 patients (3%) obtaining a complete response and 205 (29%) a partial response. The median duration of response was 13.1 months and the median survival time from registration was 12.6 months. Age, performance status (PS), and Rai stage correlated with survival (P < .01). Grade 4 hematologic toxicity was reported in 43% and was associated with infection in 22%. Neurotoxicity (primarily grade 1 motor dysfunction) was reported in 14% patients and correlated with age. CONCLUSION: This study describes the toxicity and activity of fludarabine in refractory CLL in a setting that more closely resembles clinical practice than most published trials. The low response rate may be related to advanced stage (89% Rai high-risk), disease-related symptoms (63% had B symptoms), and/or degree of prior treatment. Other contributing factors inherent in a group C treatment protocol included lack of central pathology review, variable supportive care, and a tendency to use this mechanism at a later stage in the disease.

Current Status of U.S. Clinical Trials in Chronic Lymphocytic Leukemia.

Current therapies for chronic lymphocytic leukemia (CLL) have not substantially improved the survival of these patients (pts). As a result treatment has been primarily palliative. One major obstacle in designing innovative therapies has been a lack of new and effective agents. Recent interest in clinical trials has been stimulated by the impressive activity in pts with CLL of three unique purine analogues; fludarabine (FLUDARA), 2'-deoxycoformycin (DCF) and 2-chlorodeoxyadenosine (CDA). Of the three, the largest experience in CLL is with FLUDARA. More than 1200 CLL patients have received FLUDARA either on clinical trials or through the NCI-Group C protocol mechanism. In contrast to the published data, preliminary analysis of the first 87 evaluable Group-C patients revealed only 2% complete and 37% partial responses; this discrepancy can be explained by the fact that most patients were still receiving treatment at the time of the analysis, and many were continuing to respond (9 of 12 patients who received treatment for > 6 cycles responded); there was no central pathology review to confirm the diagnosis, 89% were Rai "high risk", and most patients had received extensive prior therapy. An updated analysis of response in the first 300 cases is underway. Of 497 pts evaluable for toxicity, 41% developed infections which were serious in 17%, and there were episodes of serious neurotoxicity in 9%. Based on the high level of activity and relative tolerability of FLUDARA, a national U.S. phase III trial is underway comparing chlorambucil (CLB) vs FLUDARA vs CLB + FLUDARA in untreated patients with advanced disease. A comparison of FLUDARA vs CDA in relapsed/refractory pts is being planned. Combination regimens are being piloted in relapsed/refractory CLL including DCF + FLUDARA, DCF + CLB, FLUDARA + CDA, FLUDARA + interferon-alpha, FLUDARA + gallium, FLUDARA + cyclophosphamide. Since FLUDARA achieves true complete responses in a substantial number of previously untreated pts, it is being considered as part of an induction program prior to autologous bone marrow transplantation. FLUDARA has a high degree of bioavailability in dogs, and an oral preparation is being evaluated in clinical trials. Hopefully, new purine analogue-based combination regimens will improve the response rate and survival in patients with CLL.