Marilyn Raney

Treatment of chronic lymphocytic leukemia using chlorambucil and prednisone with or without cycle-active consolidation chemotherapy .A southeastern cancer study group trial

Patients with untreated chronic lymphocytic leukemia (CLL) received protocol treatment with 6 months of chlorambucil (CB) (30 mg/M2) and prednisone (P) (80 mg/d × 5) every 2 weeks. Complete and partial responders (CR, PR) were then randomized to consolidation with six more courses of CB and P or to four courses of cytosine arabinoside (25 mg/M2 every 12 hours × 8, subcutaneously) and cyclophosphamide (25 mg/M2 every 12 hours × 8, orally) every three weeks. Of the 178 eligible patients entered, 138 (78%) were evaluable for induction therapy which produced a 22% hematologic CR and an overall response rate (CR + PR) of 74%. Eighty‐two patients received adequate consolidation, at the end of which 43 were in CR. No difference was seen in response or survival between the two consolidation treatments. Responders had longer survival than nonresponders (P = 0.0001) even when a 6‐month ‘guarantee time’ was excluded, but there was no survival difference between CR and PR. Thus, intermittent CB and P is a well‐tolerated, useful therapy for CLL but the addition of cyclophosphamide and cytosine arabinoside does not improve results.

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.

Long-term survival in adult acute lymphoblastic leukemia: follow-up of a Southeastern Cancer Study Group trial.

Current observation was obtained for adults treated on a protocol for acute lymphoblastic leukemia, which was open from 1972 to 1978, in order to determine the long-term outcome and to evaluate potential prognostic factors. Long-term survival (five + years) was seen in 32% (25/79) of patients who achieved complete remission; 16/79 remain in first remission and 2/79 are currently in second remission. Young age (less than 40) and female sex were significant prognostic factors for long-term survival, but the basis for this advantage is unclear. Further improvements in chemotherapy are needed.

Alternating sequential combination chemotherapy in the management of advanced hodgkin's disease a southeastern cancer study group trial

The Southeastern Cancer Study Group has explored the use of alternating sequential combination chemotherapy in advanced Hodgkins disease. Two hundred twelve evaluable patients were randomly assigned to treatment with the six‐drug combination, BCNU, cyclophosphamide, vinblastine, procarbazine, prednisone, and bleomycin (BCVPP‐Bleo) or with the same drugs alternating in monthly cycles with doxorubicin, dacarbazine, and bleomycin. Both regimens produced complete response rates of approximately 73%. The duration of remission and survival were similar for the two treatment regimens. Although our sequence of combinations does not rigorously meet the criteria for “non‐cross‐resistant” our results do not lend support to the hypothesis that alternating sequential non‐cross‐resistant drug combinations improves the outcome in advanced Hodgkins disease.

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 <4% blasts in the marrow had significantly longer remission durations than those with blasts ≥1% (P < 0.01). Those with hypercellular marrows had significantly shorter remission (P < 0.05) and survival (P < 0.01). The transient presence of more than 3% blasts in the blood also was suggestive of a shorter remission duration and survival.

Treatment of Residual Disease in AML: Interim Analysis of a Southeastern Cancer Study Group Prospective Randomized Clinical Trial

Therapeutic results for patients with acute myelogenous leukemia have improved dramatically over the past decade. The effective use of cytosine arabinoside (Ara-C) combined with anthracycline antibiotics as induction therapy has resulted in complete remission rates of 60–75% (1–3). Several series of patients from individual institutions or collaborating institutions testing novel chemotherapy strategies have demonstrated that up to 50% of their patient populations can achieve prolonged disease free survival (4–8). Among the strategies reported to be successful in prolonging remission duration are the use of prolonged intensive cytotoxic therapy (4), brief intensive therapy using multiple non-cross resistant drugs (8), consolidation with high dose Ara-C (7), intensive timed sequential therapy with daunorubicin and Ara-C (6), and consolidation with intensive chemoradiotherapy followed by allogeneic or syngeneic bone marrow transplantation (9–14). When the data is viewed in the aggregate, allogeneic bone marrow transplantation during first remission has resulted in a higher proportion and a greater number of long term survivors than any other treatment strategy. A recent update from the International Bone Marrow Transplantation Registry indicates that 45% of 418 patients transplanted in first remission, or 188 patients have a probability of being alive at 3 and 4 years (15).

Phase II evaluation of teniposide (VM-26) in metastatic breast carcinoma - A Southeastern Cancer Study Group trial

The Southeastern Cancer Study Group performed a Phase II study of teniposide in previously treated patients with metastatic breast cancer. No responses were observed in 11 evaluable patients who received teniposide 60 mg/m2 by IV infusion for five consecutive days every three weeks. Toxicity was primarily gastrointestinal and hematologic and was frequently severe. This study demonstrated no therapeutic activity for teniposide when given in this dose and schedule to patients with heavily pretreated metastatic breast cancer.