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Biomedical subjects

T R Fleming

Publications and source records attributed to T R Fleming.

At least 91 records · Page 5Linked to original sources
PubMed1984

Bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for adenocarcinoma confined to the prostate.

A total of 519 patients with clinical stage B disease underwent radical prostatectomy from 1966 to 1981: 65 (12.5 per cent) had pathologic stage D1, 72 (14.0 per cent) pathologic stage C and 382 (73.5 per cent) pathologic stage B disease. Of the 519 patients 320 with pathologic stage B1 (239) or B2 (81) adenocarcinoma of the prostate and no prior hormonal or radiation therapy underwent complete pelvic lymphadenectomy and radical retropubic prostatectomy. Stage, grade and size of tumor were associated significantly with interval to disease progression but not with survival. The probable explanation for this observation is that only 2 per cent of 186 patients who were followed for 5 years and 2 per cent of 46 who were followed for 10 years died of prostatic carcinoma within these intervals. The over-all survival of patients who had intracapsular prostatic carcinoma was not different from that of an age-matched surgical control group (men undergoing total hip arthroplasty during the same interval). These observations suggest that although morbidity from alternative therapies may vary no other treatment modality offers survival superior to that observed for pelvic lymphadenectomy and radical retropubic prostatectomy in patients with pathologic intracapsular prostatic cancer.

Adenocarcinoma↗
PubMed1984

Designs for group sequential tests.

Several authors have proposed group sequential procedures to satisfy the ethical need in clinical trials for interim analyses. We propose here an alternative procedure that offers a good opportunity for early termination when initial results are extreme, while essentially maintaining the power provided by the procedure that applies when the corresponding test statistic is computed only at the predetermined time of final analysis. The new design is also sufficiently flexible to readily allow one to increase the maximum number of analyses for certain reasons such as unexpectedly slow accrual into the study, although not for reasons arising from consideration of outcomes observed at interim analysis.

Clinical Trials as Topic↗
PubMed1984

Randomized study of systemic chemotherapy following complete excision of nonosseous sarcomas.

Between June 1975 and April 1981, 61 of the 177 eligible patients whose nonosseous sarcomas of extremity or trunk origin had been completely excised primarily or after local recurrences agreed to participate in a randomized study of adjuvant chemotherapy. Dermatofibrosarcoma, lymphomas, myeloma, Kaposi's sarcoma, and embryonal rhabdomyosarcoma were excluded as were patients with significant second primary cancers and those who received either preoperative or postoperative radiation therapy. After stratification by anatomic status of disease, site of origin, and histologic grade, a random one half of the 61 participants began alternating courses of vincristine/cyclophosphamide/dactinomycin, and vincristine/doxorubicin/dacarbazine at six-week intervals for one year. The control group was evaluated at six-week intervals without adjuvant chemotherapy, but these patients were offered this chemotherapy later if they had progressive disease excised. Although 30% of the 61 patients experienced local recurrence of disease within the first five years after randomization, and only 54% were continuously disease free for five or more years, 82% were surviving at five years (Kaplan-Meier calculations) with a median follow-up of 64.3 months. Partial suppression of distant metastasis by adjuvant chemotherapy was apparent in the overall study, in the extremity tumor category, and in the subgroup of patients who had received limb-sparing surgery; however, no survival advantage for chemotherapy-treated patients was demonstrated. The 30 adjuvant chemotherapy-treated patients received a total of three thoracotomies as compared with 17 salvage thoracotomies for the 31 control patients; however, salvage surgery for local recurrences has been similar in the two groups. Recent improvement in the survival of patients with soft-tissue sarcomas is not necessarily a result of adjuvant chemotherapy or radiation therapy.

Adolescent↗
PubMed1984

Comparison of combination chemotherapy programs in advanced adenocarcinoma-large cell carcinoma of the lung: a North Central Cancer Treatment Group study.

One hundred and six patients with advanced adenocarcinoma and large cell carcinoma of the lung with no prior chemotherapy were entered in a prospectively randomized trial comparing cyclophosphamide, doxorubicin, and cisplatin versus methotrexate, doxorubicin, cyclophosphamide, and lomustine. The two regimens resulted in nearly identical regression probabilities (36% vs 34%), distributions of time to progression, and survival distributions. The major toxic effects from both regimens consisted primarily of myelosuppression and nausea and vomiting, with severe vomiting occurring more frequently in patients treated with cyclophosphamide, doxorubicin, and cisplatin (43% vs 19%).

Adenocarcinoma↗
PubMed1983

Course of localized adenocarcinoma of the prostate treated by radical prostatectomy.

Among 562 patients with histologic stage B-1, B-2, or C adenocarcinoma of the prostate treated by radical prostatectomy and pelvic lymphadenectomy, analysis revealed that increasing histologic stage, tumor size, degree of capsular invasion, seminal vesicle involvement, and histologic grade all were highly correlated with both local and systemic progression (log-rank two-sided P less than or equal to 0.0001). No variable correlated with survival--a result that may reflect appropriate adjuvant therapy given at the time of progression. The death rate from prostatic cancer did appear to rise progressively with increase of stage. Overall, the projected 10-year survival was 76%.

Adenocarcinoma↗
PubMed1983

Hormonal treatment at time of radical retropubic prostatectomy for stage D1 prostate cancer.

We classified 70 prostatic cancers as stage D1 at the time of pelvic lymphadenectomy and radical prostatectomy. For retrospective analysis after 1 to 14 years of followup, the patients were divided into 32 in whom endocrine therapy had been given immediately postoperatively and 38 in whom it had not. These 2 groups did not differ substantially in patient age, Gleason grade, pathologic stage, tumor volume or seminal vesicle involvement. The mean number of involved nodes per patient was higher in the hormone-treated group (2.9 versus 1.8). According to Kaplan-Meier projections 88 per cent of such patients without hormonal treatment will have progression within 5 years, compared to only 14 per cent of those given hormonal treatment immediately. However, projected survival differed little between the groups, most likely since 17 of the 18 patients with progression in the nontreated group were given hormonal treatment as soon as progression was substantiated. Definitive assessment of the impact of the timing of endocrine therapy on patient survival and time to disease progression awaits a randomized trial with long-term followup.

Adenocarcinoma↗
PubMed1982

A clinical trial of amygdalin (Laetrile) in the treatment of human cancer.

One hundred seventy-eight patients with cancer were treated with amygdalin (Laetrile) plus a "metabolic therapy" program consisting of diet, enzymes, and vitamins. The great majority of these patients were in good general condition before treatment. None was totally disabled or in preterminal condition. One third had not received any previous chemotherapy. The pharmaceutical preparations of amygdalin, the dosage, and the schedule were representative of past and present Laetrile practice. No substantive benefit was observed in terms of cure, improvement or stabilization of cancer, improvement of symptoms related to cancer, or extension of life span. The hazards of amygdalin therapy were evidenced in several patients by symptoms of cyanide toxicity or by blood cyanide levels approaching the lethal range. Patients exposed to this agent should be instructed about the danger of cyanide poisoning, and their blood cyanide levels should be carefully monitored. Amygdalin (Laetrile) is a toxic drug that is not effective as a cancer treatment.

Adolescent↗
PubMed1982

Cyclophosphamide plus cis-platinum in combination: treatment program for stage III or IV ovarian carcinoma.

A randomized prospective comparison of treatment with cyclophosphamide and that with cyclophosphamide and cisplatinum, each in 21 patients with advanced ovarian cancer, has shown that the time to progression of tumor and the duration of survival were markedly improved in the patients receiving the combination chemotherapy. Cytoreductive surgery was performed in most of the patients in the study before the chemotherapy regimen was initiated. Second-look surgery was performed after a year of chemotherapy. The chemotherapy was administered on an outpatient basis, without excessive toxicity. At 2 years, 52.4% of the patients receiving combination therapy had no progression of tumor, whereas 9.5% had no progression of tumor inthe group of patients receiving a single alkylating agent. Survival at 2 years was 61.9% for the combination chemotherapy group and 19.0% for those treated with cyclophosphamide alone. The study demonstrates a striking superiority of combination chemotherapy over single-agent chemotherapy in patients with advanced ovarian cancer.

Adult↗
PubMed1982

One-sample multiple testing procedure for phase II clinical trials.

Commonly, the central objective of Phase II clinical trials is the assessment of the antitumor 'therapeutic efficacy' of a specific treatment regimen. It is of interest to formulate test procedures which can be employed in these trials to decide whether or not this therapeutic efficacy warrants further investigation. For ethical reasons, these procedures should allow for early termination if initial results are extreme. In this paper, a one-sample multiple testing procedure is proposed which employs the standard single-stage test procedure at the last test, and which both allows for early termination and essentially preserves the size, power and simplicity of the single-stage procedure.

Clinical Trials as Topic↗
PubMed1981

Evaluation of alternating chemotherapy and sites and extent of disease in extensive small cell lung cancer.

Sixty-six patients were entered into a prospective, randomized clinical trial evaluating the use of alternating noncross-resistant chemotherapy in patients with extensive small cell carcinoma of the lung. Sixty-five were evaluable. One regimen utilized cyclophosphamide, VP-16, vincristine, cisplatin alternating with doxorubicin (Adriamycin) and DTIC (CVVP-AD). The second regimen utilized doxorubicin, VP-16, vincristine, and cisplatin alternating with cyclophosphamide and DTIC (AVVP-CD). There was no statistically significant difference between the two chemotherapeutic programs in terms of regression rate, time to progression, or survival. Overall regression rate for CVVP/AD was 91% (29/32) including five complete regressions (CRs). For AVVP-CD, the total regression rate was 82% (27/33) including nine CRs. Combined, the overall regression rate was 86% with a CR rate of 22%. Time to progression for CVVP-AD and AVVP-CD was 28 and 26 weeks, respectively. The median survival time of CVVP-AD and AVVP-CD regimens was 40 and 42 weeks, respectively. Prognostic variables significantly correlated with survival were performance score and extensive liver metastases at diagnosis. Correlations between initial sites of disease led to the observation that patients with no central nervous system (CNS) metastases at diagnosis were more likely to have more extensive liver and lung involvement. Further analysis revealed the lung to be the most common site of first progression (46%) and liver second (28%). Patients with extensive involvement of the liver or lung progressed sooner in these sites than those with a lesser tumor extent. At some point in the study, 40% of the patients experienced CNS metastases. The efficacy of these two alternating regimens is comparable to most current regimens reported in extensive SMCLC. Whether cyclophosphamide or doxorubicin is used first seemed to make little difference. The alternate noncross-resistant regimen was rarely effective in producing tumor regression following initial progression.

Antineoplastic Agents↗
PubMed1981

Chemotherapy for advanced head and neck cancer with the combination adriamycin, cyclophosphamide, and cis-diamminedichloroplatinum (II): preliminary assessment of a one-day vs. three-day drug regimen.

Fourteen patients with advanced head and neck carcinomas received a monthly intravenous regimen of Adriamycin, 40 mg/m2, day 1; cyclophosphamide, 400 mg/m2, day 3; and cis-diamminedichloroplatinum, 20 mg/m2/1 hour, days 1-3 (CAP-3). A regression rate of only 7% (0/12 squamous cell carcinomas; 1/2 adenocarcinomas) and a median survival of five months for all patients was accompanied by considerable gastrointestinal toxicity. These results strikingly diverge from a prior study that achieved a 64% (16/25) regression rate using comparable doses of each agent but was administered by rapid infusion on one day each month (CAP-1). Admittedly, the relatively impaired performance scores of the CAP-3 participants may have had some impact on these discouraging results. On the other hand, the maximum therapeutic efficacy of the combination Adriamycin, cyclophosphamide, and cis-platinum may well depend upon subtle interactions of cell cycle kinetics and dosage and schedule of each agent.

Adenocarcinoma↗
PubMed1981

Radical retropubic prostatectomy and pelvic lymphadenectomy for high-stage cancer of the prostate.

A series of 340 patients with adenocarcinoma of the prostate treated by bilateral pelvic lymphadenectomy and radical retropubic prostatectomy was reviewed to determine the factors that influence survival and time to progression of disease. Follow-up ranged from 1-12 1/2 years. Factors evaluated were grade, stage, and bulk of tumor; influence of seminal vesical involvement and number of pelvic nodes involved; age of patient; and year of surgery. Tumor grade was the only factor related significantly to patient survival. However, grade, stage, and bulk of tumor were all significantly associated with interval between surgery and disease progression. Furthermore, in Stage C disease, seminal vesical involvement (C+) was an adverse factor for disease progression, particularly among patients with low-grade tumor. This is in contrast to the finding that, among patients with Stage D1 disease, those with seminal vesical involvement experienced more favorable survival times and times to progression of disease when compared with patients without seminal vesical involvement. Overall, patient survival compared favorably with an age-matched control group for all stages, A through D1. Patients with few pelvic nodes involved had a survival experience nearly comparable with that of an age-matched control group. This suggests that pelvic lymphadenectomy might have a therapeutic value and that patients with pelvic nodal disease only, without evidence for metastatic disease, should not be denied radical surgery. The influence of concomitant hormonal manipulation or radiotherapy (or both) on patient survival and disease progression is not conclusively answered in this report.

Adult↗
PubMed1981

Cyclophosphamide, adriamycin, and cis-diamminedichloroplatinum (II) in the treatment of patients with advanced head and neck cancer.

Twenty-seven patients with measurable or evaluable, regionally advanced or metastatic head and neck cancer were given a combination of cyclophosphamide (C), Adriamycin (A), and cis-diamminedichloroplatinum (II) (P). Most patients had received extensive prior surgery and/or radiation therapy. Among 25 evaluable patients, the overall response rate was 64% (16/25) with 3/25 complete responders and 13/25 partial responders. The median survival for the entire group of 25 patients and the median response duration for the subset of 16 patients experiencing tumor regression were 8.1 and 7.0 months, respectively. Responders lived significantly longer than nonresponders (11 months vs. six months, P less than 0.01). According to covariate analysis, the difference seems to reflect the influence of response to treatment and not other confounding variables. Almost all patients experienced anorexia, nausea, vomiting, and a pervasive feeling of ill-health. In fact, six patients declined further treatment and five of these had objective tumor regressions. Recurrent disease was detected three months following discontinuation of chemotherapy in four of these five patients and seven months later in the fifth. Myelosuppression was clinically acceptable and there was in this dosage and schedule no evidence of hepatic or renal impairment. Although the CAP regimen has substantial antitumor activity, the program is clinically rigorous and should remain an investigational treatment modality at the present time.

Adolescent↗
PubMed1981

An evaluation of low-dose cisplatin as part of combined modality therapy of limited small cell lung cancer.

Sixty-two patients with previously untreated limited stage small cell lung cancer were treated in a prospectively randomized trial comparing thoracic irradiation plus combination chemotherapy with VP-16-213, vincristine (Oncovin), cyclophosphamide, and Adriamycin (VOCA) or those same four drugs plus low-dose (40 mg/m2) cisplatin (VOCAP). The addition of the cisplatin in eight courses of planned chemotherapy did not significantly improve either time to tumor progression of survival or alter sites of disease progression. It did, however, worsen the degree and frequency of nausea, vomiting, and myelosuppression. We did not identify any benefit from the usage of low-dose cisplatin as employed in this study.

Adult↗