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T R Fleming

Publications and source records attributed to T R Fleming.

At least 73 records · Page 4Linked to original sources
PubMed1989

Weighted Kaplan-Meier statistics: a class of distance tests for censored survival data.

A class of statistics based on the integrated weighted difference in Kaplan-Meier estimators is introduced for the two-sample censored data problem. With positive weight functions these statistics are intuitive for and sensitive against the alternative of stochastic ordering. The standard weighted log-rank statistics are not always sensitive against this alternative, particularly if the hazard functions cross. Qualitative comparisons are made between the weighted log-rank statistics and these weighted Kaplan-Meier (WKM) statistics. A statement of null asymptotic distribution theory is given and the choice of weight function is discussed in some detail. Results from small-sample simulation studies indicate that these statistics compare favorably with the log-rank procedure even under the proportional hazards alternative, and may perform better than it under the crossing hazards alternative.

Biometry↗
PubMed1988

Surgical adjuvant therapy of rectal cancer.

Surgery is the preferred method of curative therapy for carcinoma of the rectum. However, in spite of complete gross tumor resection, many patients with locally advanced tumors will experience recurrence of malignant disease in the pelvis and/or distant metastases. This article summarizes the roles of radiotherapy and chemotherapy, administered alone and in combination, as surgical adjuvant treatment for patients with resectable rectal cancer. A biostatistical overview is presented. It is concluded that strong evidence exists supporting the efficacy of combined postoperative radiotherapy and chemotherapy. Further clinical trials are indicated to determine the optimum chemotherapy regimen, sequence, and duration of the therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

5-Fluorouracil and folinic acid in the treatment of metastatic colorectal cancer: a randomized comparison. A Southwest Oncology Group Study.

In order to determine the clinical applicability of the in vitro observation of enhanced cytotoxicity of 5-fluorouracil (5-FU) in the presence of excess reduced folates, the Southwest Oncology Group (SWOG) performed a randomized trial evaluating two dose schedules of 5-FU and folinic acid (FA) in 128 patients with metastatic colorectal cancer. Of 125 eligible patients, 62 were randomized to receive bolus FA (200 mg/m2 days 1 through 4) in addition to 5-FU (1,000 mg/m2 days 1 through 4) by continuous four-day infusion (infusion arm), while 63 were randomized to receive bolus FA (200 mg/m2 days 1 through 5) in addition to 5-FU (325 mg/m2 days 1 through 5) by bolus injection (bolus arm). The toxicities of the two schedules differed, with stomatitis being more severe in the infusion arm and leukopenia being more severe in the bolus arm. The response rates and survival data for the two arms are nearly identical. The median survival of patients on the infusion arm is 11.0 months and of patients on the bolus arm, 10.3 months. The infusion arm produced one complete response (CR) and 12 partial responses (PRs), for a major response rate of 21% of eligible patients. The bolus arm produced three CRs and 11 PRs, for a major response rate of 22% of eligible patients. The response rate produced is minimally superior to recent cooperative group studies of colorectal cancer, but the response rate and survival experience are within the range of experience for treatment with 5-FU alone.

Adenocarcinoma↗
PubMed1987

Policies for study monitoring and interim reporting of results.

Interim analyses of comparative trials are necessary in order to monitor for extreme therapeutic results. However, closing studies and reporting results whenever "trends" appear increases the probability of a false conclusion to well over the desired .05 level. Guidelines for early stopping of comparative trials must be carefully defined to avoid this problem. In addition, to avoid inappropriate early closure of studies due to declining accrual (as investigators draw their own conclusions from early unreliable data), it is recommended that access to interim data be limited to a multidisciplinary monitoring committee responsible for (1) performing and reviewing interim analyses, and (2) deciding when early termination should be considered. Accrual and reporting of studies from two clinical trials groups, one with a policy of limited access to interim data and one without, are compared. The group without monitoring committees had a higher incidence of accrual and reporting problems than the group with monitoring committees.

Clinical Trials as Topic↗
PubMed1987

Cisplatin, vinblastine, and mitoguazone in squamous cell carcinoma of the esophagus: a Southwest Oncology Group Study.

Forty patients with locally extensive or metastatic squamous cell carcinoma of the esophagus were registered onto a phase II trial employing cisplatin, vinblastine, and mitoguazone. Of 36 eligible patients, four (11%) had partial responses. None had received prior chemotherapy or radiation therapy. Toxicity was mild to moderate and consisted mostly of nausea and vomiting. The activity of this regimen at the doses and schedule used was minimal. More aggressive use of therapy should be considered for further trials.

Aged↗
PubMed1985

Trial of penicillamine in advanced primary biliary cirrhosis.

A total of 227 patients with histologically advanced primary biliary cirrhosis entered a double-blind, randomized, controlled trial to determine whether penicillamine (1 g per day) was therapeutically effective; 111 patients received the drug, and 116 received placebo. The two groups were highly comparable at entry with regard to clinical, biochemical, and histologic features. Penicillamine therapy did not result in an overall improvement in survival as compared with placebo. Clinical symptoms and serial hepatic laboratory values reflected the progressive nature of the disease and were similar in both groups. There were no substantial differences between treatment groups in the morphologic features of sequential biopsy specimens. The development of major side effects led to permanent discontinuation of penicillamine in 22 per cent of the patients taking the drug. We conclude that penicillamine is not useful for patients with histologically advanced primary biliary cirrhosis. The trial is being continued in patients with early histologic disease whose better prognosis necessitates longer follow-up.

Clinical Trials as Topic↗
PubMed1985

A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma. Fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin.

Three hundred five patients with advanced pancreatic and gastric carcinoma were randomly assigned to treatment with fluorouracil, fluorouracil plus doxorubicin (Adriamycin) (FA), or fluorouracil plus doxorubicin plus mitomycin (mitomycin C) (FAM). All regimens were equivalent with regard to patient survival. There is no reasonable likelihood that either the FA or FAM regimen could produce a meaningful survival advantage over fluorouracil alone. Interval to disease progression, objective response rates, and palliative effects (improved performance, body weight, or symptoms) were essentially equivalent among the three regimens. With regard to toxicity, the FAM regimen produced more anorexia, nausea, vomiting, leukopenia, thrombocytopenia, and cumulative bone marrow suppression. Fluorouracil alone produced more stomatitis and diarrhea. Because of a failure to produce improved survival or palliation, unrewarded toxicity, and excessive cost, neither the FA nor FAM regimen can be recommended for the treatment of advanced pancreatic or gastric cancer.

Adenocarcinoma↗
PubMed1985

High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison.

It has been claimed that high-dose vitamin C is beneficial in the treatment of patients with advanced cancer, especially patients who have had no prior chemotherapy. In a double-blind study 100 patients with advanced colorectal cancer were randomly assigned to treatment with either high-dose vitamin C (10 g daily) or placebo. Overall, these patients were in very good general condition, with minimal symptoms. None had received any previous treatment with cytotoxic drugs. Vitamin C therapy showed no advantage over placebo therapy with regard to either the interval between the beginning of treatment and disease progression or patient survival. Among patients with measurable disease, none had objective improvement. On the basis of this and our previous randomized study, it can be concluded that high-dose vitamin C therapy is not effective against advanced malignant disease regardless of whether the patient has had any prior chemotherapy.

Aged↗
PubMed1985

A controlled evaluation of recent approaches to biochemical modulation or enhancement of 5-fluorouracil therapy in colorectal carcinoma.

Three hundred thirty-five previously untreated patients with advanced colorectal carcinoma were randomly assigned to treatment with 5-fluorouracil (5-FU) alone, 5-FU plus N-(phosphonacetyl)-L-aspartic acid (PALA), 5-FU plus high-dose thymidine, 5-FU plus levamisole, or 5-FU plus methyl CCNU, vincristine, and streptozotocin (MOF-Strept). Dosages were designed to produce definite toxicity in the majority of patients, although the nature of dose-limiting reactions varied considerably among regimens. 5-FU alone and 5-FU plus levamisole produced mucocutaneous reactions, diarrhea, and leukopenia; 5-FU plus PALA produced primarily mucocutaneous reactions and diarrhea; 5-FU plus thymidine produced leukopenia with occasional neurotoxicity and hypotension; and MOF-Strept produced substantial nausea and vomiting with both thrombocytopenia and leukopenia. Objective response rates among patients with measurable disease varied from 12% (5-FU plus PALA) to 34% (MOF-Strept), but none of the regimens were significantly superior to 5-FU alone. Both interval to progression and survival were comparable among the five regimens with no reasonable chance that any combination regimen could produce as much as a 50% improvement when compared with 5-FU alone. Whereas we observed definite modulation of 5-FU dose--toxicity relationships, particularly with the thymidine and PALA combinations, this did not result in a detectable improvement in therapeutic effect. None of the combination regimens, administered in the dosages and schedules we used, can be recommended as standard therapy of advanced colorectal carcinoma.

Aged↗
PubMed1985

A controlled evaluation of combined 5-fluorouracil, doxorubicin, and mitomycin C (FAM) for the treatment of advanced non-small-cell lung cancer.

One hundred eighty-six patients with advanced non-small-cell lung cancer were randomly assigned to treatment with combined 5-fluorouracil, doxorubicin, and mitomycin C (FAM) or combined methotrexate, doxorubicin, cyclophosphamide, and lomustine (MACC). Respective objective regression rates were comparable at 20% and 16%. Distribution of intervals to progression (overall median, 2.8 months) and survival times (overall median, 5.0 months) were essentially identical between the two regimens. The comparability of therapeutic effect was also evident within the subset of 81 patients who had adenocarcinoma cell type, although MACC showed a small advantage in survival after covariate analysis. In large-cell carcinoma, MACC showed a higher regression rate than that of FAM as well as a small advantage in survival. In squamous-cell carcinoma, however, FAM was superior to MACC in regression rates (32% v 4%) and also provided somewhat longer survival. With regard to toxicity, MACC produced a higher incidence of nausea and vomiting, whereas FAM produced more frequent and severe thrombocytopenia. From an overall standpoint, the therapeutic accomplishments of both regimens were disappointing. Our study does, however, provide additional evidence that mitomycin C-containing regimens may be selectively effective for squamous-cell carcinoma of the lung.

Adenocarcinoma↗
PubMed1985

Comparison of cyclophosphamide plus cisplatin versus hexamethylmelamine, cyclophosphamide, doxorubicin, and cisplatin in combination as initial chemotherapy for stage III and IV ovarian carcinomas.

Among 187 women with stage III and IV ovarian carcinoma who participated in this comparative clinical trial, 181 were eligible for analysis. Of these patients, 89 received monthly treatment with CP [cyclophosphamide (1 g/m2) plus cisplatin (60 mg/m2)] and 92 received monthly treatment with HCAP [hexamethylmelamine (150 mg/m2/day X 7), cyclophosphamide (400 mg/m2), doxorubicin (30 mg/m2), and cisplatin (60 mg/m2)]. All treatments were administered iv on Day 1 of each monthly treatment cycle, except for hexamethylmelamine, which was administered orally on Days 2-8. With a median follow-up time of 30 months, survival curves for the two treatment groups were almost identical, as were their times to progression [estimated median survival, 24.6 months (Kaplan-Meier)]. Patient characteristics which significantly influenced survival were age, degree of histologic differentiation, extent of residual disease, stage of disease, and histologic type. Results of posttreatment laparotomies have been equal for the two treatment groups. Toxic effects of the two regimens have been similar, except for more frequent, more severe, and earlier neurotoxicity among patients treated with HCAP. Of the two regimens, CP has the better therapeutic index.

Adult↗
PubMed1984

Risk of local urethral recurrence after radical cystectomy for bladder cancer.

Radical cystectomy and urinary diversion were performed on 349 patients with transitional cell cancer of the bladder. Followup for 4 to 13 years revealed that 91 and 83 per cent of the patients were free of urethral recurrence 5 and 10 years after cystectomy, respectively. Statistical elimination of urethral recurrences did not improve the over-all survival rate significantly. It appears that supplementation of cystectomy with simultaneous urethrectomy may not be justified if the urethra is not involved by the cancer.

Adult↗