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Biomedical subjects

J M Bennett

Publications and source records attributed to J M Bennett.

At least 217 records · Page 12Linked to original sources

Adjuvant CMFP versus CMFP plus tamoxifen versus observation alone in postmenopausal, node-positive breast cancer patients: three-year results of an Eastern Cooperative Oncology Group study.

After mastectomy, 265 postmenopausal patients with node-positive breast cancer were stratified according to pathologic nodal status and estrogen-receptor (ER) status and randomized to receive either 12 cycles of cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP), or CMFP plus tamoxifen (CMFPT), or observation alone. Patients entered the study between March 1978 and July 1981. Cox regression analysis indicated that, compared to observation alone, chemotherapy (CMFP and CMFPT groups combined) led to a significant reduction in relapses by the end of the first year of study in every examined prognostic subgroup. However, after the first year the relapse-free survival curves of all treatment groups tended to merge, so that by three years 52% of the observation group and 51% of the chemotherapy groups remained disease free. Chemotherapy continued to show a significantly superior relapse-free survival rate for three years only in the subgroup of patients with ER-negative tumors (the subgroup with the largest relapse-free survival advantage at one year). The addition of tamoxifen produced no benefit or harm in any prognostic subcategory examined. ER status was prognostically important for predicting early relapse only in those patients not receiving chemotherapy, due to the greater effectiveness of this chemotherapy to prevent early relapse in the ER-negative subgroup. Treatment has had no early effect on survival. As breast cancer continues to recur even after ten or more years, later relapse patterns may alter these results.

Antineoplastic Combined Chemotherapy Protocols↗

Criteria for the diagnosis of acute leukemia of megakaryocyte lineage (M7). A report of the French-American-British Cooperative Group.

For the diagnosis of M7, the bone marrow aspirate shows a leukemic cell infiltrate that comprises 30% or more of all cells. These cells are identified as being of megakaryocyte lineage by the platelet peroxidase reaction on electron microscopy or by tests with monoclonal or polyclonal platelet-specific antibodies. Myelofibrosis or increased bone marrow reticulin are a prominent aspect in most patients with M7. In patients with increased reticulin, the bone marrow sample may be difficult to obtain and the counts done on the marrow films may be misleading. In these patients, the diagnosis of M7 should be based on excellent bone marrow biopsy sections that show an excess of blasts and, at times, increased numbers of maturing megakaryocytes; and on the presence of unequivocal megakaryoblasts in the peripheral blood or bone marrow (or both) as shown by immunologic techniques.

Acute Disease↗

Effectiveness of acute nonlymphocytic leukemia induction chemotherapy in acute lymphocytic leukemia.

Twelve adults with newly diagnosed acute lymphocytic leukemia (ALL) received a combination of daunorubicin, cytarabine, and 6-thioguanine (DAT) as induction chemotherapy. Eleven patients (91%) gained complete remission (ten patients after a single course of treatment). Because DAT alone seems effective in ALL, the combination of vincristine, prednisone, and DAT could improve the complete remission rate. Moreover, the resulting early leukemic cytoreduction could enhance remission duration in adults with ALL.

Adult↗

3-[18F]Acetylcyclofoxy: a useful probe for the visualization of opiate receptors in living animals.

A fluoro-analogue of the potent narcotic antagonist, naltrexone, was synthesized and shown to bind with high affinity to opiate receptors in vitro. 3-[18F]acetylcyclofoxy was prepared via a one-step triflate displacement reaction with the positron emitting 18F ion from tetraethylammonium [18F] fluoride. 3-[18F]acetylcyclofoxy accumulation in opiate receptor rich brain regions of both rat and baboon is shown to be completely displaced by the active enantiomer of naloxone [-)-naloxone) while the identical dose of the pharmacologically inert (+)-naloxone has no detectable effect. Moreover, both rat and baboon brain showed the well documented, typical opiate receptor distribution so that basal ganglia and thalamus are clearly visible in the living baboon brain up to 95 min after intravenous injection of 3-[18F] acetylcyclofoxy. We expect that 3-[18F )acetylcyclofoxy will be a useful probe for visualizing opiate receptors in living humans.

Animals↗

Thrombolysis by intracoronary streptokinase infusion in patients with acute ischaemic syndromes.

Intracoronary streptokinase was administered to 40 patients with acute myocardial ischaemic syndromes in an effort to restore antegrade flow in the affected vessel by thrombolysis. This was successful, with total occlusion of the vessel, in 66% of cases. Restoration of antegrade flow by the intracoronary administration of nitroglycerin was successful in only 1 case (2%). Subsequent study showed that re-occlusion of an initially patent vessel had occurred in 43% of cases and that recanalization had occurred in 62% of cases in which the vessel had initially remained occluded. Complications comprised reperfusion arrhythmias (55%), serious haemorrhage (8%) and reinfarction (8%). Intracoronary thrombolysis with restoration of antegrade flow was safely achieved in the majority of cases.

Adult↗

High-dose amsacrine (AMSA) therapy of relapsed and refractory adult acute nonlymphocytic leukemia. A phase II study.

Amsacrine (AMSA) has been shown to be an effective therapeutic agent in the treatment of adult acute nonlymphocytic leukemia (ANLL). The Eastern Cooperative Oncology Group studied the efficacy and toxicity of high-dose amsacrine (200 mg/m2/day for 5 days) in 38 adult patients with refractory and relapsed ANLL. The complete remission rate was low (8%). This dose level of amsacrine caused severe mucositis in 24% of patients and marked liver function abnormalities in 11%. Seizures did not occur, and two reversible cardiac events were not clearly attributable to amsacrine administration. Escalation of amsacrine beyond currently recommended total doses of 600-750 mg/m2 is unlikely to be of benefit.

Acute Disease↗

A phase II trial of VP 16-213 in adults with refractory acute myeloid leukemia. An Eastern Cooperative Oncology Group study.

VP-16-213 was studied in 38 adult patients with relapsed or refractory acute myeloid leukemia as part of a randomized trial in an ECOG master protocol. In this group of heavily pretreated patients, an overall response rate of 18% was achieved (5% CR, 13% PR). Toxicity was mild, and aplasia was rarely observed. Responses were seen in all of the FAB myeloid subtypes. Patients who had never achieved remission status responded as well as patients who had relapsed.

Adult↗

A critical comparison of allogeneic bone marrow transplantation and conventional chemotherapy as treatment for acute nonlymphocytic leukemia.

Published data from two centers conducting bone marrow transplantation on patients with acute nonlymphocytic leukemia in first remission were pooled and compared with results from an Eastern Cooperative Oncology Group (ECOG) study in which patients were treated with conventional chemotherapy. A series of adjustments were made to the ECOG sample to account for selection factors that restrict access of patients to transplantation. The transplant sample exhibits considerably higher disease-free survival when compared to the adjusted ECOG series (53% versus 21% at three years). The transplant series is somewhat younger than the ECOG series (median, 24 years versus 28 years). The impact of age on the disease-free survival results is difficult to assess because of the relatively small samples in the different age groups. However, by defining a suitable control group, methodology for making a critical comparison between the two modalities is presented which, if applied to larger samples of patients, should help to resolve the issue. In the absence of data from a large, prospective randomized study, a critical retrospective comparison of available data is essential in the assessment of treatment options.

Acute Disease↗

Full dose versus attenuated dose daunorubicin, cytosine arabinoside, and 6-thioguanine in the treatment of acute nonlymphocytic leukemia in the elderly.

Between July 1, 1981 and November 1, 1982, 45 patients with acute nonlymphocytic leukemia (age, greater than or equal to 70 years) were randomly assigned to receive induction chemotherapy using either daunorubicin, cytosine arabinoside, and 6-thioguanine in full dosage (F DAT) or an attenuated schedule of the same drugs (At DAT) as part of an Eastern Cooperative Oncology Group controlled trial. Forty patients were deemed evaluable, 20 on each arm. The overall complete remission (CR) rate for all patients in both arms was 28% (11/40). There was no significant difference in CR rates between the two arms. There were 12 early deaths (less than 60 days) in the F DAT arm compared with only five early deaths on the At DAT arm (P = .05). Due primarily to this early death rate, the median survival for the F DAT group was 29 days v 159 days for the At DAT groups (P = .02). The range of survival of the patients in CR for the At DAT group given either one or two cycles of induction therapy was 121 to 414 days, while the survival range for the F DAT CR patients was 121-186 + days. The median survival for those not achieving CR was 14 days for the F DAT group v 80 days for the At DAT (P less than .02). Fifty-nine percent of the At DAT patients spent greater than 100 days out of the hospital v 12% for the F DAT group. Attenuated chemotherapy with lower doses of DAT is the preferred induction regimen for elderly patients with acute nonlymphocytic leukemia since it causes fewer early deaths, allows a better quality of life, and yields survival times as durable as intensive therapy.

Acute Disease↗

A randomized study of the efficacy of consolidation therapy in adult acute nonlymphocytic leukemia.

The Eastern Cooperative Oncology Group conducted a randomized study to determine the efficacy of consolidation therapy in prolonging the duration of complete remission (CR) in adults with acute nonlymphocytic leukemia (ANLL). Induction chemotherapy with daunorubicin, cytosine arabinoside, and 6-thioguanine (DAT) yielded CR in 65% of 283 patients with ANLL, aged 16-69. For patients aged 60-69, the CR rate was 58%. Of 184 patients in CR, 146 patients were then randomized to receive either maintenance therapy with weekly cytosine arabinoside and 6-thioguanine alone (69 patients) or two courses of reduced doses of DAT 1 mo apart, before commencing the same maintenance program (77 patients). Consolidation therapy resulted in hematologic toxicity, but was not lethal in any of the eligible patients. Patients receiving consolidation plus maintenance therapy experienced a longer CR duration (40 wk) and disease-free survival at 2 yr (28%) than did those patients receiving maintenance therapy alone (34 wk and 14%, respectively). These differences are not statistically significant. These results suggest that approaches to consolidation therapy employing reduced doses of the induction therapy regimen can have, at best, only a small benefit. For consolidation therapy to provide substantial improvement in CR duration, intensive regimens with non-cross-resistant drugs will be required.

Acute Disease↗