A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study.

Interest in high-dose cytarabine (HDAC) for both induction and postremission therapy for acute myeloid leukemia (AML) prompted the Southwest Oncology Group (SWOG) to initiate a randomized trial comparing HDAC with standard-dose cytarabine (SDAC) for remission induction of previously untreated AML and to compare high-dose treatment versus conventional doses for consolidation therapy. Patients less than 65 years of age with de novo or secondary AML were randomized for induction between SDAC 200 mg/ m2/d for 7 days by continuous infusion or HDAC at 2 g/ m2 intravenously every 12 hours for 12 doses; both groups received daunorubicin (DNR) at 45 mg/m2/d intravenously for 3 days. Complete responders to SDAC were randomized to receive either two additional courses of SDAC plus DNR or one course of HDAC plus DNR. Complete responders to HDAC were nonrandomly assigned to receive one additional course of HDAC plus DNR. Of patients randomized between SDAC (n = 493) and HDAC (n = 172) induction, 361 achieved complete remission (CR). The CR rate was slightly poorer with HDAC: 55% versus 58% with SDAC for patients aged less than 50, and 45% (HDAC) versus 53% (SDAC) for patients aged 50 to 64 (age-adjusted one-tailed P = .96). With a median follow-up time of 51 months, survival was not significantly better with HDAC (P = .41); the estimated survival rate at 4 years was 32% (HDAC) versus 22% (SDAC) for those aged less than 50, and 13% (HDAC) versus 11% (SDAC) for those aged 50 to 64. However, relapse-free survival was somewhat better following HDAC Induction (P = .049): 33% (HDAC) versus 21% (SDAC) at 4 years for those aged less than 50, and 21% (HDAC) versus 9% (SDAC) for those aged 50 to 64. Induction with HDAC was associated with a significantly increased risk of fatal (P = .0033) and neurologic (P < .0001) toxicity. Among patients who achieved CR with SDAC, survival and disease-free survival (DFS) following consolidation randomization were not significantly better with HDAC compared with SDAC (P = .77 and .46, respectively). Patients who received both HDAC induction and consolidation had the best postremission outcomes; however, the proportion of CR patients who did not go on to protocol consolidation therapy was more than twice as high after HDAC induction compared with SDAC. Induction therapy with HDAC plus DNR was associated with greater toxicity than SDAC plus DNR, but with no improvement in CR rate or survival. Following CR induction with SDAC, consolidation with HDAC increased toxicity but not survival or DFS. In a nonrandomized comparison, patients who received both HDAC induction and consolidation had superior survival and DFS compared with those who received SDAC induction with either SDAC or HDAC consolidation.

A prospective evaluation of the roles of allogeneic marrow transplantation and low-dose monthly maintenance chemotherapy in the treatment of adult acute myelogenous leukemia (AML): a Southwest Oncology Group study.

Between February 1982 and December 1986, the Southwest Oncology Group conducted a prospective study in patients with newly diagnosed acute myeloid leukemia (AML) with two objectives: to evaluate the role of allogeneic marrow transplantation for patients in first remission, and to evaluate the role of low-dose monthly maintenance therapy in those patients not transplanted in first remission. Among 522 evaluable patients, 295 (57%) achieved complete remission (CR), including 70% of patients age 49 or less. Twenty-four patients (15%) age 49 or less in CR were not HLA-typed, mostly because of financial constraints. HLA-identical donors were found for 39% of patients, of whom two-thirds were transplanted in first CR. The 5-year disease-free survival among those transplanted in first CR, those with donors not transplanted in first CR, and those less than age 50 without donors was 41, 42, and 29%, respectively (P = 0.60). A total of 150 eligible patients were randomized to receive late intensification alone or late intensification plus monthly maintenance. In multivariate analyses, treatment with maintenance was associated with prolonged disease-free survival (P = 0.028), but not improved overall survival (P = 0.27). Factors associated with improved overall survival included younger age, lower white blood count (WBC) at diagnosis, having leukemia of M3 morphology, and being of white race. In this study, a diagnosis of M3 AML was particularly favorable, with disease-free and overall survivals of 75 and 56%, respectively, at 7 years.

Phase II trial of didemnin-B in advanced epithelial ovarian cancer. A Southwest Oncology Group study.

A Phase II study of Didemnin-B, a marine cyclic depsipeptide, was undertaken in patients with progressive epithelial ovarian cancer. The starting dose was 2.6 mg/m2. Fifteen patients received the drug, of whom twelve were evaluable. There were no responses observed in the twelve patients. The two most frequent toxicities were nausea and vomiting and anemia. On the basis of this trial, Didemnin-B is not felt to have significant effect with epithelial ovarian cancer.

Clinical cancer research in Louisiana.

The Ochsner Medical Institutions of New Orleans and Baton Rouge, the Louisiana State Medical Centers in New Orleans and Shreveport, and the Tulane Medical Center of New Orleans are all actively involved in the conduct of National Cancer Institute approved and sponsored clinical trials. Through the efforts of investigators at these institutions, avant-garde, state-of-the-art cancer clinical trials are being made available to the citizens of the state of Louisiana.

A comparison of metoclopramide vs. droperidol/phenobarbital for emesis induced by chemotherapy.

Chemotherapy-induced nausea and vomiting cause morbidity and poor compliance among patients receiving intensive cancer chemotherapy. High-dose antiemetic regimens, while effective, add significantly to the cost of treatment. This study compares the efficacy and cost of high-dose metoclopramide with a combination of phenobarbital and droperidol. All patients treated were naive to prior chemotherapy, and all patients received treatment regimens containing cisplatinum. Both antiemetic regimens proved equally efficacious in suppressing emesis, but the phenobarbital/droperidol combination achieved a 100-fold decrease in cost.

Institutional performance in application of the FAB classification of acute leukemia. The Southwest Oncology Group experience.

Institutional performance in application of the French-American-British (FAB) classification of acute leukemia in The Southwest Oncology Group is presented, demonstrating a disparity between institutional and expert performance. A significant improvement is shown with an educational effort coupled with experience in use of the classification, and the importance of cytochemistry in the use of the classification is illustrated. A simplification of the classification, merging M1, M2, and M4 as M7, is proposed. This simplification improves institutional performance in use of the classification, while preserving distinctions that appear clinically important.

Reproducibility of the French-American-British classification of acute leukemia: the Southwest Oncology Group Experience.

After initial French-American-British (FAB) diagnosis by a multiinstitutional Southwest Oncology Group panel, slides of acute leukemia cases were recirculated to panel members for second review. The reproducibility of the FAB classification is analyzed. The classification is reproducible in the 70% range in panel reviewer hands and allows remarkable reproducibility in the morphologic and cytochemical distinction of acute lymphoid leukemia (ALL) from acute myeloid leukemia (AML). The limitations of a morphologic and cytochemical classification of acute leukemia are discussed. A simplification of the FAB system, merging M1, M2, and M4 as M7, is proposed; this simplification improves the system's reproducibility.

Genetic studies in multiple myeloma. 1. Association with HLA-Cw5.

Human leukocyte antigens (HLA) were identified in 22 black Americans with multiple myeloma. No significant association was observed between antigens at either the A or the B locus. At the C locus, in contrast, HLA-Cw5 was more prevalent in the patient group, four of 22 having it, compared with the control group, in which two of 138 individuals possessed it. All four patients with HLA-Cw5 were males. Those results suggest that genetic factors, perhaps in conjunction with an environmental change, may be responsible for the recent increase in incidence in myeloma in black Americans, especially in males.

Doxorubicin and ifosfamide combination chemotherapy in previously treated acute leukemia in adults: a Southwest Oncology Group pilot study.

The Southwest Oncology Group did a limited institutional pilot study of the combination of doxorubicin and ifosfamide in the treatment of previously treated adult patients with acute leukemia. Thirty-four patients received one or two courses of the combination. All patients had received prior chemotherapy and 32 had received prior anthracycline chemotherapy. Three patients died before their responses could be fully evaluated. Fourteen patients achieved complete remission (41%) and one patient achieved partial remission. The complete remission rate was 27% for patients with acute myeloblastic leukemia (myelomonoblastic leukemia, monoblastic leukemia, and erythroleukemia) and 89% for patients with acute lymphocytic and undifferentiated leukemia (ALL). Toxic effects included severe hematologic reactions in 33 of 34 patients, hematuria in six patients, altered sensorium in one patient, and congestive heart failure in one patient. The safety of the combination was established and toxic side effects of this therapy were tolerable. The 89% complete remission rate for previously treated patients with ALL suggests that the combination of doxorubicin and ifosfamide may be particularly effective in ALL.