Therapy of acute myelogenous leukemia in patients over the age of 50: a randomized Southeastern Cancer Study Group trial.

In a randomized trial, 299 evaluable patients with acute myelogenous leukemia, age greater than or equal to 51, were initially randomized to cytosine arabinoside, 100 mg/m2/day, by continuous intravenous infusion for seven days, plus either daunorubicin 45 mg/m2/day x 3 (DA), or m-AMSA 200 mg/m2/day x 3 days (MA). Complete remission (CR) rates were not significantly different, 47% for DA and 42% for MA. Toxicities were similar except that severe hepatic toxicity, serum bilirubin greater than or equal to 7 mg/dl, was more frequent in patients receiving MA (10%) than in patients receiving DA (4%), p less than 0.05. Deaths during induction were significantly more frequent in patients receiving MA (38%) than in patients receiving DA (25%), p = 0.018. Patients achieving a CR received thioguanine, cytosine arabinoside, and daunorubicin (TAD) for three cycles as consolidation. Among evaluable patients, 82/102 (80%) stayed in CR during these three cycles. Patients were then randomized to either no maintenance or to DA every 13 weeks x 4 cycles, at a dose slightly lower than used for induction. Remission duration was similar for the two maintenance programs, 10.7 months for no maintenance and 8.5 months for DA. The percentage of patients evaluable for maintenance achieving three year relapse-free survival was similar for the two maintenance programs, 28% for no maintenance and 21% for DA. However, overall survival was significantly greater (40 vs 12 months, p = 0.007) for patients receiving no maintenance therapy, due to greater survival after recurrence in these patients. At each phase of the study there were substantial numbers of non-evaluable cases, often due to incomplete evaluation of remission status. Of the 379 patients initially entered into the trial, 35% obtained a complete remission. Of all the patients who achieved a complete remission, 61% were both evaluable and in remission upon completion of the maintenance phase. Of these patients who completed the maintenance phase in remission, 15% were relapse free survivors three years following initiation of maintenance therapy. Overall, only 3.2% of patients who entered the trial (35% x 61% x 15%) were continuous relapse-free survivors three years into the maintenance phase.

Prognostic significance of blood and marrow findings in acute myelogenous leukemia in remission. A Southeastern Cancer Study Group report.

Bone marrow and peripheral blood findings at the time of complete remission were analyzed in 333 patients with acute myelogenous leukemia to determine if any variables were predictive for remission duration and survival. Patients were categorized as to percentage of blasts, promyelocytes, erythroid precursors and lymphocytes in the marrow and hemoglobin concentration, leukocyte and platelet counts, and percentage of granulocytes and blasts in the blood. Additionally, the degree of cellularity in the marrow aspirate and biopsy were analyzed. Patients with less than 1% blasts in the marrow had significantly longer remission durations than those with blasts greater than or equal to 1% (P less than 0.01). Those with hypercellular marrows had significantly shorter remission (P less than 0.05) and survival (P less than 0.01). The transient presence of more than 3% blasts in the blood also was suggestive of a shorter remission duration and survival. The presence of less than 1% blasts in the marrow, normal or decreased biopsy cellularity, and no anemia at the time of remission defined a "good" prognostic group. The quality of remission should be assessed in evaluating the results of therapy and assigning further treatment.

A randomized comparison of postremission therapy in acute myelogenous leukemia: a Southeastern Cancer Study Group trial.

The Southeastern Cancer Study Group conducted a post-remission induction randomized trial in adult acute myelogenous leukemia to assess the efficacy of alternate drug therapy during consolidation and of immunotherapy during maintenance. Of 508 evaluable patients entered into the study, 335 (66%) achieved a complete remission treated with a 7-day infusion of cytosine arabinoside at a dose of 100 mg/sq m/day and 3 days of daunorubicin at a dose of 45 mg/sq m/day. Those in remission were randomized to receive 3 courses of 1 of 3 consolidation regimens: (A) a continuous infusion of 5-azacytidine, 150 mg/sq m/day for 5 days; (B) 5-azacytidine plus beta-deoxythioguanosine, 300 mg/sq m/day for 5 days; or (C) cytosine arabinoside, 100 mg/sq m/day intravenously, and thioguanine, 100 mg/sq m orally every 12 hr, plus daunorubicin, 10 mg/sq m every 24 hr daily for 5 days. There was no difference in relapse rate among the 3 arms. Those completing consolidation and remaining in remission were randomized to 1 of 3 maintenance regimens: (D) chemotherapy, 5-day infusion of cytosine arabinoside and 2 days of daunorubicin (same doses as induction) given every 13 wk for 1 yr; (E) BCG given twice weekly for 1 mo and then monthly for 1 yr; or (F) the combination of regimens D and E. The median duration of remission was significantly better on regimen D (17.4 versus 9.4 and 9.5 mo), and median survival was 29 mo compared to 21 mo for the other regimens. Those given different drugs during consolidation than used for induction (regimens A and B) and subsequent chemotherapy for maintenance (regimen D) had the longest remission durations and survival. Immunotherapy was not as good as intensive chemotherapy for maintenance.

Physicians' opinions of expanded clinical pharmacy services.

A statistical interaction model explaining 27 per cent of the variation in physicians' attitudes toward clinical pharmacy among 180 Alabama physicians is presented. Young primary care physicians who prescribe drugs with a low risk of adverse reactions are the most favorable toward pharmacists practicing clinical tasks. Older solo-practice physicians who lack exposure to clinical pharmacy are the least favorable. The implications for the wider acceptance of clinical pharmacy are discussed in terms of its resources of professional power. (Am J Public Health 1983; 73:96-101.)

Effect of exposure on physicians' attitudes toward clinical pharmacists.

The effect of exposure to clinical pharmacists on physicians' favorability toward clinical pharmacy was studied. Questionnaires were sent to 576 physicians belonging to a county medical society. The survey measured the extent to which physicians agreed that hospital pharmacists should: (1) maintain drug profiles, (2) monitor prescribing patterns of physicians to preempt adverse reactions, (3) counsel patients at bedside, (4) decide on the frequency of use and dosage forms of physician-prescribed drugs, and (5) independently choose the drug to be prescribed based in the physician's diagnosis. A Guttman scale of task favorability was computed and compared four respondent groups: (1) physicians unaware of clinical tasks being practiced in hospitals, (2) physicians aware of clinical services but not knowing the clinical pharmacists, (3) physicians knowing the pharmacists but not working with them, and (4) physicians working with clinical pharmacists. There were 180 usable responses. While all groups were unfavorable to pharmacists independently choosing drugs, the physicians in groups exposed to pharmacists were favorable toward pharmacists counseling patients (p less than 0.001) and deciding on frequency of use and dosage forms of physician-prescribed drugs (p less than 0.05). More than 90% of the physicians working with clinical pharmacists ranked their quality of work as good or excellent. Exposure was related to specialty, risk of malpractice claim, and participation in hospital meetings. Exposure had a positive effect on the favorability of physicians toward clinical pharmacists and their services.

Medical role-task boundary maintenance: physicians' opinions on clinical pharmacy.

Mailed questionnaires were analyzed for 100 physicians concerning their favorability toward allowing clinical pharmacists to perform role tasks which potentially encroach on the physician's role. A Guttman Scale of Task Favorability was computed and revealed that physicians were unfavourable to those pharmacy tasks that allow pharmacists to make independent technical-therapy decisions. Physicians were favorable toward clerical and patient-management tasks, but only as adjunct tasks to the physician's role. Generally, older physicians, those with a high risk of malpractice suit and those who write a large number of prescriptions, were least favorable to pharmacists expanding their roles. Younger physicians, those who spend a high proportion of their practice time in hospitals and those who have had previous experience with clinical pharmacists were most favorable. The analysis was framed in the theoretical context of professional power and professional role-boundary maintenance.