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T P Miller

Publications and source records attributed to T P Miller.

At least 19 recordsLinked to original sources
PubMed1998

Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma.

BACKGROUND: Patients with clinically localized, intermediate- or high-grade non-Hodgkin's lymphoma usually receive initial treatment with a doxorubicin-containing regimen such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Pilot studies suggest that eight cycles of CHOP alone or three cycles of CHOP followed by involved-field radiotherapy are effective in such patients. METHODS: We compared these two approaches in a prospective, randomized, multi-institutional study. The end points were progression-free survival, overall survival, and life-threatening or fatal toxic effects. Two hundred eligible patients were randomly assigned to receive CHOP plus radiotherapy, and 201 received CHOP alone. RESULTS: Patients treated with three cycles of CHOP plus radiotherapy had significantly better progression-free survival (P=0.03) and overall survival (P=0.02) than patients treated with CHOP alone. The five-year estimates of progression-free survival for patients receiving CHOP plus radiotherapy and for patients receiving CHOP alone were 77 percent and 64 percent, respectively. The five-year estimates of overall survival for patients receiving CHOP plus radiotherapy and for patients receiving CHOP alone were 82 percent and 72 percent, respectively. The adverse effects included one death in each treatment group. Life-threatening toxic effects of any type were seen in 61 of 200 patients treated with CHOP plus radiotherapy and in 80 of 201 patients treated with CHOP alone (P=0.06). The left ventricular function was decreased in seven patients who received CHOP alone, whereas no cardiac events were recorded in the group receiving CHOP plus radiotherapy (P=0.02). CONCLUSIONS: Three cycles of CHOP followed by involved-field radiotherapy are superior to eight cycles of CHOP alone for the treatment of localized intermediate- and high-grade non-Hodgkin's lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Cognitive and noncognitive symptoms in dementia patients: relationship to cortisol and dehydroepiandrosterone.

We investigated the relationship between basal cortisol and dehydroepiandrosterone (DHEA) levels and impairment in different cognitive and noncognitive measures and the possible interaction of DHEA with hypercortisolemia in dementia in 27 patients diagnosed with Alzheimer's disease (AD). There were 17 men and 10 women. Patients were mildly to moderately cognitively impaired at the time of the initial cortisol measures. Patients were administered the Alzheimer's Disease Assessment Scale (ADAS) and Folstein Mini-Mental State Examination (MMSE) at approximately 6-month intervals. Cortisol and DHEA were determined using conventional 125I radioimmunoassay procedures. Pearson product-moment correlations among cortisol and DHEA measures and both initial and longitudinal clinical measures were calculated. There was a relationship between baseline 8 a.m. cortisol levels and cognitive function at the initial testing as measured by the ADAS cognitive measure, with higher cortisol levels being associated with a greater level of impairment. We did not document a relationship between cortisol or DHEA levels and noncognitive measures. There was a significant correlation between both the initial MMSE and ADAS cognitive measures and initial DHEA level, with lower DHEA levels unexpectedly being associated with better performance on these measures. The initial DHEA levels did not predict decline in cognitive function over time. These findings bring into question the potential usefulness of DHEA as a therapeutic agent.

Aged↗
PubMed1998

A phase I/II trial of paclitaxel for non-Hodgkin's lymphoma followed by paclitaxel plus quinine in drug-resistant disease.

Patients with non-Hodgkin's lymphoma (NHL) recurrent after chemotherapy exhibit clinical characteristics compatible with the phenomenon of multidrug resistance (MDR) and frequently have detectable levels of P-glycoprotein (P-gp). Paclitaxel has been used in recurrent NHL with limited success. To test whether clinical resistance to paclitaxel can be reversed, we treated patients having paclitaxel-resistant NHL with paclitaxel plus quinine and measured the effects of quinine on paclitaxel pharmacokinetics. Eligible patients had recurrent and measurable NHL. Patients initially received paclitaxel, 120 mg/m2 (dose determined by a phase I trial of paclitaxel plus quinine), as a 20-24 h infusion every 3 weeks until there was evidence of clinical resistance. Patients then received paclitaxel at the same dose rate plus oral quinine at a fixed dose rate of 400 mg three times each day. Paclitaxel pharmacokinetics were studied in each patient using paired samples from plasma obtained at the end of the 24 h paclitaxel infusion as an estimate of the steady-state drug level. Of 14 patients treated with paclitaxel alone, one patient obtained a partial response (7%). At the time of disease progression, one patient (same patient) obtained a partial response with paclitaxel plus quinine (7%). Steady-state paclitaxel levels were obtained in 12 patients. In 11 of 12 patients the steady-state paclitaxel level was substantially lower with the addition of quinine. The average ratio of end of infusion plasma levels (paclitaxel alone/paclitaxel plus quinine) was 0.6 (range 0.31-0.97) indicating a 40% decrease in paclitaxel levels with the addition of quinine (p=0.001). We conclude that paclitaxel given by this dose and schedule has modest activity in recurrent NHL. The addition of quinine to paclitaxel also has limited activity, but the combination did reverse paclitaxel resistance in one patient, adding support to the hypothesis that clinical drug resistance can be overcome with chemosensitizers in individual patients. Pharmacokinetic studies indicate that the reversal of drug resistance in this study cannot be attributed to changes in clearance of paclitaxel (which appears to increase with quinine), but more likely to the sensitization of lymphoma cells.

Adolescent↗
PubMed1998

New REAL clinical entities.

PURPOSE: In 1994, the International Lymphoma Study Group proposed a "Revised European-American Lymphoma (REAL) Classification of Lymphoid Neoplasms." This classification system was developed because (1) new lymphoid disease entities have been recognized that are not part of the National Cancer Institute Working Formulation (WF) and (2) there was a need to develop a common classification system that could be used internationally. The REAL classification itself had never been tested, however, to determine whether it was reproducible or defined distinct clinicopathologic entities. Therefore, in the past two years, two studies were conducted by the South-west Oncology Group (SWOG) Lymphoma Committee and the Non-Hodgkin's Lymphoma (NHL) Classification Project to validate the REAL classification. PATIENTS AND METHODS: The SWOG Lymphoma Committee reviewed the pathology and clinical course of 376 previously untreated patients with stage III or IV disease within WF categories A, B, C, D, or E who received full-dose cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) in SWOG studies 7204, 7426, and 7713. No patients in this database had localized mucosa-associated lymphoid tissue (MALT) lymphoma. The NHL Classification Project performed a retrospective study of 1,403 consecutive patients with previously untreated NHL seen between 1988 and 1990 at nine sites around the world. Five expert hematopathologists reached a consensus diagnosis on every case by using histologic, clinical, and immunophenotypic data, and 20% of all cases were randomly reviewed. RESULTS: The most common diagnosis was diffuse large B-cell lymphoma (31%), which combines the large-cell and immunoblastic WF categories (WF G/H). The next most common diagnosis was follicular lymphoma (22%; WF B, C, and D). Marginal zone B-cell (including MALT), peripheral T-cell, small B-lymphocytic, and mantle cell lymphoma each constituted between 5% and 10% of diagnoses. Primary mediastinal large B-cell, anaplastic large T/null cell, high-grade B-cell, Burkitt-like, and precursor T-lymphoblastic lymphoma made up the remaining 10 most frequent diagnoses. CONCLUSIONS: The analyses conducted by the SWOG Lymphoma Committee and the NHL Classification Project have demonstrated that the REAL classification does define "real" clinical entities that can be diagnosed by expert hematopathologists. The understanding gained from study of "real" entities should permit hematologists/oncologists to better predict the clinical course of their patients and also to develop improved therapy.

Helicobacter Infections↗
PubMed1997

A Southwest Oncology Group perspective on the Revised European-American Lymphoma classification.

In recent years several new morphologic entities and a new classification system, Revised European-American Lymphoma Classification (REAL), have been proposed which affect the nomenclature and classification of lymphoid malignancies. This article reviews some of the features of the more common new entities, places these entities in immunologic context, explores the clinical utility of these entities, and provides a working clinical organization to the names.

Evaluation Studies as Topic↗
PubMed1997

Follicular lymphomas: do histologic subtypes predict outcome?

There has been a long history of debate as to whether histologic subtypes of follicular lymphoma are associated with unique outcomes. The controversy has been fueled by studies of small patient groups having heterogeneous prognostic factors followed for short intervals, and by a new proposal for the classification of lymphomas (REAL). The current report provides insight into the controversy by using a large group of patients of similar stage and treatment followed for up to 25 years.

Adult↗
PubMed1995

A clinical analysis of two indolent lymphoma entities: mantle cell lymphoma and marginal zone lymphoma (including the mucosa-associated lymphoid tissue and monocytoid B-cell subcategories): a Southwest Oncology Group study.

The objectives of this study were (1) to determine the clinical presentation and natural history associated with two newly recognized pathologic entities termed mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL), including the mucosa-associated lymphoid tissue (MALT) and monocytoid B-cell subcategories, and (2) to determine whether these entities differ clinically from the other relatively indolent non-Hodgkin's lymphomas with which they have been previously classified. We reviewed the conventional pathology and clinical course of 376 patients who had no prior therapy; had stage III/IV disease; were classified as Working Formulation categories A, B, C, D, or E; and received cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) on Southwest Oncology Group (SWOG) studies no. 7204, 7426, or 7713. All slides were reviewed by the three pathologists who reached a consensus diagnosis. Age, sex, performance status, bone marrow and/or gastrointestinal involvement, failure-free survival, and overall survival were compared among all the categories. We found that (1) MCL and MZL each represent approximately 10% of stage III or IV patients previously classified as Working Formulation categories A through E and treated with CHOP on SWOG clinical trials; (2) the failure-free survival and overall survival of patients with MZL is the same as that of patients with Working Formulation categories A through E, but the failure-free survival and overall survival of the monocytoid B-cell patients were higher than that of the MALT lymphoma patients (P = .009 and .007, respectively); and (3) the failure-free survival and overall survival of patients with MCL is significantly worse than that of patients with Working Formulation categories A through E (P = .0002 and .0001, respectively). In conclusion, patients with advanced stage MALT lymphomas may have a more aggressive course than previously recognized. Patients with MCL do not have an indolent lymphoma and are candidates for innovative therapy.

Adolescent↗
PubMed1994

Low-dose involved field radiation after chemotherapy in advanced Hodgkin disease. A Southwest Oncology Group randomized study.

OBJECTIVE: To determine if low-dose involved field radiation after complete remission induction with chemotherapy is effective in preventing relapse and improving survival in patients with stage III or IV Hodgkin disease. DESIGN: A randomized controlled trial with a median follow-up time of 8.1 years. SETTING: A Southwest Oncology Group multi-institutional study. Patients were entered from university- and community-based practices. PATIENTS: 278 adults with clinical or pathologic stage III or IV Hodgkin disease, who achieved complete responses after 6 cycles of MOP-BAP (nitrogen mustard, vincristine, prednisone, bleomycin, doxorubicin, and procarbazine) and who agreed to be randomly assigned to either radiation or no further treatment. INTERVENTION: Patients were assigned to either no further treatment or low-dose radiation to all initially involved sites (radiation dose, 2000 cGy to lymph node areas and 1000 to 1500 cGy to other involved organ sites). MEASUREMENTS: Differences in remission duration, relapse-free survival, and survival. RESULTS: Remission duration, relapse-free survival, and overall survival were similar for the two groups (P = 0.09, P > 0.2, and P = 0.14, respectively). Factors that predicted shorter remission duration in a multivariate analysis were nodular sclerosis histology, bulky disease, and receipt of less than 85% of planned chemotherapy. Low-dose radiation improved remission duration in the subgroups of patients with nodular sclerosis and bulky disease. For the 169 patients with nodular sclerosis, the 5-year remission-duration estimate was 82% for the low-dose radiation group and 60% for the no further treatment group (P = 0.002). For all patients with bulky disease, the 5-year remission-duration estimate was 75% for the low-dose radiation group and 57% for the no further treatment group (P = 0.05). No difference in overall survival was noted between low-dose radiation and no further treatment in all patients or major subgroups. The 5-year survival was 86% for all patients who had a complete response as well as for patients in the nodular sclerosis subgroup. CONCLUSIONS: Low-dose involved field radiation after MOP-BAP chemotherapy in patients with stage III or IV Hodgkin disease did not prolong remission duration or overall survival in randomized patients. However, remission duration was prolonged in several subgroups of patients, most prominently in those with nodular sclerosis histology.

Adolescent↗
PubMed1994

Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas: a prospective Southwest Oncology Group trial.

The growth fraction of tumors from patients with non-Hodgkin's lymphomas (NHL) has been shown to correlate with survival in retrospective studies. The growth fraction can be evaluated using immunohistochemical techniques employing the Ki-67 monoclonal antibody (MoAb) that marks a nuclear protein present in cycling cells. The purpose of this study was to evaluate the clinical utility of the Ki-67 MoAb for predicting survival. Using a prospective trial design in a multi-institutional cooperative trials group, the proliferative index, clinical outcome, and statistical correlations were independently assessed for previously untreated patients with advanced stages of intermediate- and high-grade histologies of NHL treated on Southwest Oncology Group study (SWOG 8516, Intergroup 0067). The proportion of Ki-67-positive cells was determined on snap-frozen thin tissue sections. A proliferative index of 80% or greater, as determined from prior retrospective studies, identified a group of patients (18%) who had a poor outcome. Overall survival was significantly reduced in these patients with a high Ki-67-associated proliferative index compared with those with a low proliferative index (P = .001). One-year survival estimates were 82% (low proliferative index) versus 18% (high proliferative index). A multivariate regression analysis incorporating commonly used clinical prognostic features confirmed the independent effect of proliferation on survival (relative risk estimate 5.9; 95% confidence interval, 2.2, 16.1). The Ki-67 MoAb identifies a group of patients with rapidly fatal NHL for whom currently available chemotherapy is inadequate.

Adult↗
PubMed1994

Phase II evaluation of mitoxantrone plus cis-platinum in patients with advanced breast cancer. A Southwest Oncology Group study.

The Southwest Oncology Group studied the response rate and toxicity of mitoxantrone (7.5 or 10 mg/m2 to 12.0 mg/m2) and cis-platinum (100 mg/m2) in 30 patients with advanced breast cancer as second-line therapy. There were 2 partial responses in 29 eligible patients. Toxicity was considerable, with 27 patients having grade 3 or 4 toxicity. Grade 3-4 toxicity included vomiting, thrombocytopenia, granulocytopenia, leukopenia and anemia. The combination of mitoxantrone plus cis-platinum has minimal activity as second-line therapy in metastatic breast cancer.

Adult↗
PubMed1994

A phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B in patients with intermediate- or high-grade non-Hodgkin's lymphoma: results of SWOG-8516 (Intergroup 0067), the National High-Priority Lymphoma Study.

BACKGROUND: CHOP is a four-drug, first-generation combination chemotherapy regimen that has cured approximately 30% of all patients with advanced stages of intermediate- or high-grade non-Hodgkin's lymphoma in national cooperative group trials. Initial single-institution studies of third-generation regimens such as m-BACOD, ProMACE-CytaBOM, and MACOP-B suggested that 55%-60% of these patients might be cured. PATIENTS AND METHODS: In order to make a valid comparison between these regimens, the Southwest Oncology Group and the Eastern Cooperative Oncology Group initiated a randomized phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B. Endpoints of the study were response rate, time to treatment failure, overall survival, and severe or life-threatening toxicity. Received dose intensity calculations and subset analyses were also performed. RESULTS: 1138 patients were registered on this clinical trial. Each treatment arm contained between 218 and 233 eligible patients. Known prognostic factors were equally distributed. The initial results of this study were recently published. There were no significant differences in either the partial or complete response rates between treatment arms. Now after a median follow-up of 49 months and a maximum follow-up of 84 months, there is still no difference in time to treatment failure (p = 0.40) or overall survival (p = 0.68). No subset of patients was found to have significantly improved survival with the third-generation regimens. The received dose intensity data were comparable to previously published data for these regimens. Fatal toxicity was 1% for CHOP, 3% for ProMACE-CytaBOM, 5% for m-BACOD, and 6% for MACOP-B. CONCLUSION: Based on similar failure-free and overall survival with lower cost and lower severe toxicity, CHOP remains the standard chemotherapy for patients with advanced-stage, intermediate- or high-grade non-Hodgkin's lymphoma. New treatment strategies need to be developed to improve the prognosis of these patients.

Aged↗
PubMed1994

The presence of bcl-1 and bcl-2 gene rearrangements in diffuse small cleaved-cell lymphoma. A disease with diverse molecular and immunophenotypic findings.

Clonal rearrangements of the bcl-1 and bcl-2 protooncogenes are found in many B-lineage non-Hodgkin's lymphomas (NHL) and may play a role in their pathogenesis. We investigated rearrangements of the bcl-1 and bcl-2 protooncogenes in 13 cases of B lineage diffuse small cleaved-cell lymphoma (DSCL), and correlated the results with clinical history, immunophenotype, and outcome. Six cases showed bcl-2 rearrangements, including four patients with an antecedent follicular small cleaved-cell lymphoma (FSCL). Two patients had a bcl-1 rearrangement, including one with a previous FSCL. Of the five patients who lacked detectable bcl-1 or bcl-2 rearrangements, one had an FSCL history. Similar to the lack of correlation between clinical history and genotype, there was no correlation between genotype and immunophenotype. Our results indicate that although DSCL is a morphologically uniform disease, different molecular genetic pathways are involved in its genesis. Follow-up showed four of the six DSCL patients with bcl-2 rearrangements were alive with a median survival of 56 months, whereas the median survival of the seven patients lacking a bcl-2 rearrangement was 17 months and included only one survivor. Thus bcl-2 rearrangements in DSCL may define a patient subset with a more indolent genetic abnormality and prolonged survival.

Adult↗
PubMed1993

Radiation therapy salvage of Hodgkin's disease following chemotherapy failure.

PURPOSE: This study evaluates the efficacy of comprehensive salvage radiation therapy, with or without chemotherapy, in selected patients with Hodgkin's disease who have failed primary combination chemotherapy. METHODS AND MATERIALS: Between 1972 and 1991, 28 patients with advanced Hodgkin's disease failing intensive combination chemotherapy in previously unirradiated nodal and/or pulmonary sites were treated with salvage radiotherapy with curative intent. Treatment consisted of comprehensive extended field radiotherapy to all known areas of disease. Total radiation doses ranged from 17.0 to 50.0 Gy, with only five patients (18%) receiving < 30.0 Gy to any field. Twelve patients also received chemotherapy as part of their salvage regimen. RESULTS: Twenty-six patients (93%) achieved a complete response and 14 (50%) remain in continuous complete remission at 14 to 133 months. In addition, three patients (11%) who failed salvage radiotherapy are now without evidence of disease following additional therapy. With a median follow-up of 47 months (range 14+ to 198+), actuarial median relapse-free survival and overall survival are 46 and 97 months, respectively. Actuarial 5-year relapse-free survival and overall survival are 40% and 63%, respectively. Patients with an initial complete response to chemotherapy had a significantly longer actuarial relapse-free survival than those with an initial partial response (p = 0.02). Salvage therapy was generally well-tolerated and resulted in no treatment-related deaths. CONCLUSION: Comprehensive salvage radiotherapy is of significant benefit in selected patients and should be considered an option for patients with advanced Hodgkin's disease following chemotherapy failure.

Adolescent↗
PubMed1993

Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma.

BACKGROUND: CHOP is a first-generation, combination-chemotherapy regimen consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone that has cured approximately 30 percent of patients with advanced stages of intermediate-grade or high-grade non-Hodgkin's lymphoma in national cooperative-group trials. However, studies at single institutions have suggested that 55 to 65 percent of such patients might be cured by third-generation regimens such as ones consisting of low-dose methotrexate with leucovorin rescue, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD); prednisone, doxorubicin, cyclophosphamide, and etoposide, followed by cytarabine, bleomycin, vincristine, and methotrexate with leucovorin rescue (ProMACE-CytaBOM); and methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B). METHODS: To make a valid comparison of these regimens, the Southwest Oncology Group and the Eastern Cooperative Oncology Group initiated a prospective, randomized phase III trial. The study end points were the response rate, time to treatment failure, overall survival, and incidence of severe or life-threatening toxicity. Dose intensity was calculated and analyzed. RESULTS: Of the 1138 patients registered for the trial, 899 were eligible. Each treatment group contained at least 218 patients. Known prognostic factors were equally distributed among the groups. There were no significant differences among the groups in the rates of partial and complete response. At three years, 44 percent of all patients were alive without disease; there were no significant differences between the groups (41 percent in the CHOP and MACOP-B groups and 46 percent in the m-BACOD and ProMACE-CytaBOM groups; P = 0.35). Overall survival at three years was 52 percent (50 percent in the ProMACE-CytaBOM and MACOP-B groups, 52 percent in the m-BACOD group, and 54 percent in the CHOP group; P = 0.90). There was no subgroup of patients in which survival was improved by a third-generation regimen. Fatal toxic reactions occurred in 1 percent of the CHOP group, 3 percent of the ProMACE-CytaBOM group, 5 percent of the m-BACOD group, and 6 percent of the MACOP-B group (P = 0.09). CONCLUSIONS: CHOP remains the best available treatment for patients with advanced-stage intermediate-grade or high-grade non-Hodgkin's lymphoma.

Adolescent↗