Biomedical subjects

B Y Yeap

Publications and source records attributed to B Y Yeap.

11 recordsLinked to original sources

PubMed2001

The effect of surgery and grade on outcome of gastrointestinal stromal tumors.

HYPOTHESIS: Gastrointestinal stromal tumors (GIST) are aggressive, rare, and difficult-to-cure gastrointestinal tumors. We believe that the clinical behavior of these tumors can be predicted by reproducible prognostic factors. DESIGN AND SETTING: A retrospective review of all patients (N = 70) with GIST treated at a tertiary care center from 1973 to 1998. PATIENTS: Adequate data for evaluation were available for 69 patients. Male-female distribution was 40:29. Median age was 60 years. Median follow-up duration was 38 months. MAIN OUTCOME MEASURES: Tumor grade, stage, and histologic subtype at presentation; effect of grade, surgery and adjuvant therapy on recurrence, salvage, and survival. RESULTS: Tumor distribution included 61% in the upper, 23% in the middle, and 16% in the lower digestive tract, with a median tumor size of 7.9 cm (range, 1.8-25 cm). Tumors with more than 1 mitosis per 10 high-power fields constituted 57% of neoplasia in the series. Distant disease at initial visit occurred in 49% of patients. Complete gross resection occurred in 59% of patients. After complete resection, the 5-year survival rate was 42%, compared with 9% after incomplete resection (hazard ratio = 0.27, P<.001). Neither radiation nor chemotherapy demonstrated any significant benefit. Among 39 patients who were disease free after complete resection, 2% developed lymph node recurrence, 25% developed local recurrence, and 33% developed distant recurrences (54% liver, 20% peritoneum). By multivariate analysis the risk of local and/or distant metastases was significantly increased for tumors with more than 1 mitosis and size larger than 5 cm (P<.05). Multivariate analysis in all 69 patients revealed that incomplete resection, age greater than 50 years, non-smooth muscle histological feature, tumor with more than 1 mitosis, and tumor size larger than 5 cm significantly decreased survival. CONCLUSION: Complete gross surgical resection is presently the only means of cure for GIST. Tumors with more than 1 mitosis and a size larger than 5 cm have an especially poor prognosis, with decreased survival, and increased local and/or distant recurrence.

Adolescent↗

PubMed2001

Megestrol and tamoxifen in patients with advanced endometrial cancer: an Eastern Cooperative Oncology Group Study (E4882).

To investigate the effect of adding tamoxifen to megestrol in the hormonal therapy for advanced endometrial cancer, 66 patients were entered in this study. Initially, 41 patients were randomized to either the standard progestin therapy of megestrol or to the combination of megestrol and tamoxifen between October 1982 and October 1984. The megestrol arm was terminated because of poor accrual and 25 patients were directly assigned to the combination arm. Among the 20 eligible cases on the megestrol arm, the response rate of 20% consisted of I complete response and 3 partial responses. The response rate on the megestrol plus tamoxifen arm was 19% with 1 (2%) complete response and 7 (17%) partial responses among 42 eligible cases. The median survival times were 12.0 months and 8.6 months, respectively. Only mild and moderate toxicities were observed on megestrol compared with more toxic complications observed on the combination of megestrol and tamoxifen, including a life-threatening case of pulmonary embolism. Although we could not carry out a comparative evaluation as intended, we conclude that the combination of megestrol and tamoxifen offers no clinical advantage over megestrol alone in the treatment of advanced endometrial carcinoma.

Aged↗

PubMed2001

Robust two-stage estimation in hierarchical nonlinear models.

Hierarchical models encompass two sources of variation, namely within and among individuals in the population; thus, it is important to identify outliers that may arise at each sampling level. A two-stage approach to analyzing nonlinear repeated measurements naturally allows parametric modeling of the respective variance structure for the intraindividual random errors and interindividual random effects. We propose a robust two-stage procedure based on Huber's (1981, Robust Statistics) theory of M-estimation to accommodate separately aberrant responses within an experimental unit and subjects deviating from the study population when the usual assumptions of normality are violated. A toxicology study of chronic ozone exposure in rats illustrates the impact of outliers on the population inference and hence the advantage of adopting the robust methodology. The robust weights generated by the two-stage M-estimation process also serve as diagnostics for gauging the relative influence of outliers at each level of the hierarchical model. A practical appeal of our proposal is the computational simplicity since the estimation algorithm may be implemented using standard statistical software with a nonlinear least squares routine and iterative capability.

Air Pollutants↗

PubMed1998

Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomized trials. Advanced Ovarian Cancer Trialists' Group.

The purpose of this systematic study was to provide an up to date and reliable quantitative summary of the relative benefits of various types of chemotherapy (non-platinum vs platinum, single-agent vs combination and carboplatin vs cisplatin) in the treatment of advanced ovarian cancer. Also, to investigate whether well-defined patient subgroups benefit more or less from cisplatin- or carboplatin-based therapy. Meta-analyses were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths. The results suggest that platinum-based chemotherapy is better than non-platinum therapy, show a trend in favour of platinum combinations over single-agent platinum, and suggest that cisplatin and carboplatin are equally effective. There is no good evidence that cisplatin is more or less effective than carboplatin in any particular subgroup of patients.

Antineoplastic Agents↗

PubMed1994

Trimetrexate in advanced hormone-refractory prostate cancer. An ECOG phase II trial.

The antitumor activity and toxicity of trimetrexate (TMTX) was evaluated in measurable, hormone-refractory, advanced prostate cancer patients. Patients were required to have an ECOG performance status < 3, bidimensionally measurable disease, serum creatinine < or = 1.5 mg/dL, normal bone marrow function, and adequate hepatic function. Prior non-hormonal systemic therapy, active infection, third space effusions were exclusion criteria. TMTX 12 mg/m2 daily for five days (8 mg/m2 for patients with any prior radiation therapy or age > or = 75 years) was administered every 3 weeks. There were no responses in the 18 eligible patients. Median time to treatment failure and median survival were 6 and 20 weeks, respectively. Myelosuppression was the most frequent toxicity observed and was mild to severe in all but 4 patients. Two patients whom experienced life-threatening reversible leukopenia and grade 4 thrombocytopenia developed in 2 further patients. Non-hematologic toxicity was also reversible and was mild to severe. TMTX at this dose and schedule is inactive in advanced, hormone-refractory prostate cancer.

Aged↗

PubMed1993

Taxol in advanced, hormone-refractory carcinoma of the prostate. A phase II trial of the Eastern Cooperative Oncology Group.

BACKGROUND: Recent clinical trials have documented activity for combinations of chemotherapeutic agents that target the microtubular apparatus in patients with hormone-refractory prostate cancer. Taxol has a novel antimicrotubular mechanism, acting by stabilizing polymerized tubulin. METHODS: Twenty-three patients with hormone-refractory prostate cancer and bidimensionally measurable disease were treated with Taxol by 24-hour continuous infusion at 135-170 mg/M2 every 21 days for a maximum of 6 cycles. RESULTS: Eighty-five courses of Taxol were administered to 23 patients. One patient (4.3%) experienced a partial response lasting 9 months, and four other patients with radiographically stable disease had minor reductions in the serum prostate-specific antigen (PSA) of 16-24%. Eleven patients (47.8%) had stable disease, and progressive disease developed in 9 patients (39.1%) during therapy. Median survival was 9 months. Leukopenia was the dose-limiting toxicity with 13% of patients having Grade 3 and 61% having Grade 4 toxicity, and granulocytopenic fever developed in 26%. Three patients experienced sudden cardiovascular events while participating in the study, including one patient with a nonfatal, non-Q-wave myocardial infarction that occurred during a taxol infusion, and two patients who had sudden deaths 9 days and 30 days after receiving their last taxol dose, respectively. CONCLUSIONS: In the subset of patients with hormone-refractory prostate cancer and bidimensionally measurable disease, Taxol at this dosage has only minor activity.

Aged↗

PubMed1991

Drug-related pulmonary toxicity in non-Hodgkin's lymphoma. Comparative results with three different treatment regimens.

Pulmonary toxicity may complicate the treatment of non-Hodgkin's lymphoma (NHL). The possible drug-related cause of pulmonary toxicity was investigated retrospectively in 207 NHL patients treated between 1981 and 1988 with three regimens containing cyclophosphamide with and without methotrexate or bleomycin: methotrexate, calcium, leucovorin, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) (n = 134); methotrexate, calcium, leucovorin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-ACOD) (n = 43); or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (n = 30) chemotherapy. These regimens contained the same drugs and were administered in the same schedule; the regimens differed primarily in the addition of bleomycin or methotrexate. Pulmonary toxicity occurred in 24 of 134 (18%) m-BACOD-treated and in six of 43 (14%) m-ACOD-treated patients (P = 0.65). Chest radiography revealed diffuse pulmonary infiltrates in 16 (67%) and six (100%) of the m-BACOD-treated and m-ACOD-treated patients with pulmonary toxicity, respectively. None of the CHOP-treated patients had pulmonary toxicity. The clinical features of pulmonary toxicity and the amount of chemotherapy administered before it occurred did not differ in patients treated with m-BACOD or m-ACOD, although the toxicity tended to be more severe in the m-BACOD group. Open lung or transbronchial biopsies done in six (38%) of the m-BACOD-treated and three (50%) of the m-ACOD-treated patients with pulmonary infiltrates revealed nonspecific pneumonitis compatible with drug-related toxicity. In summary, these results showed that pulmonary toxicity during m-BACOD and m-ACOD therapy occurred with similar frequency and clinicopathologic features. This suggested that bleomycin was not responsible uniquely for the pulmonary toxicity in m-BACOD-treated patients. That pulmonary toxicity was not observed in patients treated with CHOP suggested that methotrexate may play an important role in the pathogenesis of the pulmonary toxicity.

Adult↗

PubMed1991

Value of follow-up procedures in patients with large-cell lymphoma who achieve a complete remission.

Salvage therapy for relapsed large-cell lymphoma (LCL) is more effective in patients with minimal disease, suggesting that early detection of relapse might increase the chance of long-term survival. To determine whether current follow-up procedures are effective in identifying preclinical disease, we analyzed patterns of relapse in 139 LCL patients who achieved a complete remission (CR) with high/moderate-dose methotrexate with leucovorin, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (M/m-BACOD). The timing and results of all posttreatment follow-up tests were examined in the 36 patients who relapsed from complete remission (CR) and 46 controls who remain in CR. Despite conscientious posttreatment follow-up, only two of the 36 relapses (6%) were detected before the development of symptoms. Sixty-seven percent of patients relapsed in new disease sites (42% in new and old sites, and 25% in new sites only). Consistent with this observation, the tests most sensitive to clinical relapse were those not targeted to specific sites of disease: gallium scan (sensitivity, 90%), physical examination (80%), and lactate dehydrogenase (LDH) (65%). Of screening tests performed, only LDH was successful in detecting preclinical relapse, with a sensitivity of 42% and specificity of 85% for impending symptomatic relapse. These results indicate that conventional screening was ineffective in detecting preclinical relapse in LCL patients. We recommend prospective evaluation of a strategy that (1) screens with a frequency appropriate to a patient's risk of relapse, (2) uses sensitive test(s) not targeted to specific sites, and (3) limits aggressive screening to those high-risk patients eligible for potentially curative salvage therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Treatment of low-grade and intermediate-grade lymphoma with intensive combination chemotherapy results in long-term, disease-free survival.

To define the role of intensive combination chemotherapy in the treatment of low-grade or intermediate-grade lymphomas, the authors report results in 49 patients treated with intermediate-dose or high-dose methotrexate, bleomycin, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cytoxan (cyclophosphamide), vincristine, and dexamethasone (m/M-BACOD) with long-term follow-up. The complete response rate was 59% (29 of 49), including 67% (eight of 12) with low-grade and 57% (21 of 37) with intermediate-grade disease. The median survival for the entire group was 81 months. The 29 complete responders had a long median survival of 131 months. Forty-five percent (13 of 29) of the complete responders, 27% of the entire group, continue in remission with a median disease-free survival of 76 months. This includes five of 19 patients with diffuse poorly differentiated lymphoma, a disease generally characterized by early relapse. Twelve patients achieved a partial response and had a shorter median survival of 53 months, whereas nonresponders survived a median of less than 5 months. Late relapse was noted in patients with low-grade and intermediate-grade disease. Age (younger than or older than 60 years) was the only predictor of long-term survival. These data indicate very long disease-free survival can be achieved in low-grade and intermediate-grade lymphomas after attaining a complete remission. Intensive doxorubicin containing chemotherapy can be considered as an option for patients with advanced low-grade lymphoma but can only be proven to be superior to single-agent chemotherapy or no initial therapy by controlled randomized trails.

Adult↗

PubMed1990

The m-BACOD combination chemotherapy regimen in large-cell lymphoma: analysis of the completed trial and comparison with the M-BACOD regimen.

One hundred thirty-four assessable patients with stage II-IV large-cell lymphoma (LCL) were treated with the combination chemotherapy regimen methotrexate with leucovorin, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) between July 1981 and May 1986. The m-BACOD regimen substituted moderate-dose methotrexate (200 mg/m2 x 2) for the high-dose methotrexate used in the preceding M-BACOD regimen; all other drugs were administered as with m-BACOD. Eighty-two patients (61%) in the completed m-BACOD trial achieved a complete response (CR). With a median follow-up of 3.6 years, 62 patients (76%) continue in CR. Predicted survivals of 1, 3, and 5 years for the entire m-BACOD group are 80%, 63%, and 60%, respectively, with a 5-year disease-free survival (DFS) of 74% for the patients who achieve CR. The results obtained with m-BACOD are comparable with those obtained in the preceding M-BACOD trial, which now has a median follow-up of 8.0 years. The reduction in methotrexate dosage in m-BACOD patients was not associated with an increased incidence of CNS relapse. Long-term follow-up of the 215 M/m-BACOD patients indicates that the regimens are not associated with an increased incidence of secondary malignancy. Prolonged follow-up also indicates that advanced-stage patients have a persistent rate of late relapse of about 7.0% per year for years 2 to 5 of their follow-up and that stage II patients have an approximate 2.1% per year rate of late relapse. Application of the previously described prognostic factor model to the 215 M/m-BACOD patients from the completed trials identifies a high-risk group of patients with a CR rate and predicted 5-year survival (38% and 24%, respectively) that are significantly worse than those of the group as a whole (65% and 57%, respectively).

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1987

The m-BACOD combination chemotherapy regimen in the treatment of diffuse large cell lymphoma.

The m-BACOD regimen attempted to lower the dose of methotrexate in the M-BACOD (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone) program. Between July 1981 and January 1985, 87 previously untreated or minimally treated patients with diffuse large cell lymphoma were treated with the m-BACOD regimen (methotrexate 200 mg/m2 on days 8 and 15, bleomycin 4.0 mg/m2 on day 1, doxorubicin 45 mg/m2 on day 1, cyclophosphamide 600 mg/m2 on day 1, vincristine 1.0 mg/m2 on day 1, and dexamethasone 6 mg/m2 on days 1 to 5; leucovorin was given 24 hours after methotrexate at 10 mg/m2 every six hours for eight doses orally). Of 86 evaluable patients, 59 (68.5%) had a complete remission (CR). Partial response was seen in 21 patients with six still surviving (5 to over 15 months). Of the seven patients who had no change, all have died. The median duration of follow-up for the entire series was 30 months (range, 2 to 61). Relapse from CR occurred in 15 of 59 (25%). Currently, 56 of 87 patients (64%) survive; all but 12 are in their first remission. Overall survival was 84% for those achieving an apparent CR. The major toxic effect of the m-BACOD regimen was myelosuppression with severe leukopenia and fever, which required hospitalization for about 33% of patients. Mucositis occurred in 39 patients; 19 had severe mucositis. No significant difference in overall survival was seen between the high-dose methotrexate M-BACOD and the low-dose m-BACOD regimens.

Adult↗