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Biomedical subjects

R Gelman

Publications and source records attributed to R Gelman.

At least 109 records · Page 6Linked to original sources
PubMed1982

Comparison of induction chemotherapies for metastatic breast cancer. An Eastern Cooperative Oncology Group Trial.

Patients with advanced breast carcinoma and no prior chemotherapy were prospectively evaluated to assess the induction capabilities of cyclophosphamide, methotrexate and 5-fluorouracil (CMF), Adriamycin and vincristine (AV), and CMF plus prednisone (CMFP). The crossover responsiveness from CMF or CMFP to AV and of AV to CMF were also assessed. A disproportionate randomization led to 166 analyzable cases on AV, 79 on CMF were also assessed. A disproportionate randomization led to 166 analyzable cases on AV, 79 on CMF and 86 on CMFP induction. One hundred and twelve patients were evaluated on crossover. Induction response rates were similar with 56% on AV, 57% on CMF and 63% on CMFP. Crossover response rates ranged from 32% to 41%. CMFP and AV were superior to CMF in terms of response duration (P = 0.05), and CMFP was superior to either in terms of time to treatment failure (P = 0.04), and survival (P = 0.03). Treatment failures occurred in only the on-study organ sites of disease in 73% of the patients and did not appear to be related to the response achieved. CMF was associated with more thrombocytopenia than either AV or CMFP (P = 0.03). AV was associated with fewer infections than CMFP (P = 0.02), less diarrhea than CMFP (P = 0.04), more emesis than CMF (P = 0.02), and more neurologic toxicity than either CMF or CMFP (P less than 0.0001). There was also more emesis with CMF than with CMFP (P = 0.006). CMFP was associated with greater delivery of CMF than was the CMF regimen despite a similar day 1 leukocyte distribution. These results strongly suggest that CMF(P) and AV are clinically noncross-resistant regimens, that AV and CMF are essentially equivalently active induction regimens, and that CMFP is superior to CMF and AV.

Aged↗
PubMed1982

Quality control for estrogen receptor quantification by dextran-coated charcoal assay: a single laboratory's experience.

Wide fluctuations in results obtained by different laboratories for the content of estrogen receptors from a single source of tissue powder were reported by several investigators at the 1979 NCI Consensus Committee Meeting for Steroid Receptors in Breast Cancer and were further supported by data collected by our laboratory for the Eastern Cooperative Oncology Group. In a multilab study the inconsistency in the receptor content is a product of the variations associated with the assay procedures used by different laboratories and those due to unavoidable daily changes in the experimental conditions within each laboratory. In this report we present data on the variation of estrogen receptor measurements obtained by a single laboratory for any single source of tissue powder repeatedly analyzed. A retrospective analysis of the data collected on the receptor content of several different batches of calf uteri analyzed on different days (inter-assay variation) under uniform conditions revealed a coefficient of variation averaging +/- 35% (standard deviation divided by mean X 100). Experiments showed that the fluctuations in the receptor yield from aliquots of the same tissue powder are primarily an effect of the homogenization step that precedes cytosol preparation. Therefore, for establishing quality control, distribution of lyophilized cytosols should precede lyophilized powders to test the efficiency of performance of laboratories. A homogenizer designed to minimize thermal denaturation is also essential.

Animals↗
PubMed1982

Corrected group prognostic curves and summary statistics.

A method is presented for correcting distribution function estimators for distortions in the joint distribution of covariates in the subsamples receiving different treatments. This form of standardization is useful for depicting multivariate analyses and predicting population behavior. Furthermore, it also proves useful for comparing two trials which differ in patient mix and for adjusting estimates for know imbalances in patient characteristics. Standardization though important, is not often used in clinical trials because of the complexities introduced by multiple covariates. The proposed method overcomes these difficulties in a wide class of analyses.

Age Factors↗
PubMed1982

Randomized evaluation of combination chemotherapy vs. observation alone following response or stabilization after oophorectomy for metastatic breast cancer in premenopausal women.

Premenopausal patients with progressive measurable metastatic breast cancer who demonstrated either stable or responsive disease 12 weeks following oophorectomy were randomized either to receive cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) combination chemo-therapy (20 patients) or to continue under observation alone (14 patients). Since the study began in 1974, data on receptor status were not required for entry into the study. Stratification for randomization was based on the nature of the oophorectomy response (stable vs. response), dominant metastatic site (visceral vs. osseous vs. soft tissue), and disease-free interval (greater than 2 years vs. lesser than 2 years). Three (21%) of the 14 patients under observation alone continued to improve whereas 6 of 18 (33%) of the patients given CMF improved further, an insignificant difference. The median time to failure from oophorectomy was 17.5 months for the CMF group and 6.1 months for the observation group (p = 0.01). Using a multivariate proportional hazards model, visceral disease (p = 0.05) and breast involvement (p = 0.001) were also associated with significantly shorter times to failure. After the randomization, the fraction of observation patients progressing within 8 weeks was significantly greater than that of the CMF patients (5/14 vs. 0/21, p = 0.01). With 9 of the 14 observation patients and 11 of the 20 CMF patients dead, the estimated median survivals are similar at 40.4 and 41.3 months, respectively. We conclude that the addition of CMF chemotherapy to patients with stable-disease or objective response following oophorectomy significantly increases the median duration to treatment failure, whereas there appears to be no survival advantage for such therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1981

Phase II trials of Baker's antifol, bleomycin, CCNU, streptozotocin, tilorone, and 5-fluorodeoxyuridine plus arabinosyl cytosine in metastatic breast cancer.

A total of 202 patients with advanced breast cancer were entered into two prospectively randomized Phase II trials conducted by the Eastern Cooperative Oncology Group, in an effort to identify promising agents and combinations for previously treated cases. Patients in Study 1 received bleomycin, CCNU, or streptozotocin and those in Study 2 received tilorone, Baker's antifol, or a combination of 5-fluorodeoxyuridine plus arabinosyl cytosine. Partial responses were seen only with bleomycin, Baker's antifol, and 5-fluorodeoxyuridine plus arabinosyl cytosine. The median times to treatment failure ranged from 3.6 weeks to 5.7 weeks, and the median survival times, from 8 weeks to 25 weeks for tilorone and bleomycin, respectively. Toxic reactions was primarily hematologic and gastrointestinal, but skin, neurologic, respiratory, and renal abnormalities were noted in some treatment arms. The treatment schedules outlined and the toxic effects noted provide background information that might prove useful in designing complex new chemotherapeutic programs, since there is pharmacological rationale for incorporating some of the agents tested into present standard combination chemotherapy regimens.

Antineoplastic Agents↗
PubMed1981

A prospective evaluation of chemohormonal therapy remission maintenance in advanced breast cancer.

From October 1973 to October 1977 the ECOG prospectively evaluated cyclophosphamide, methotrexate, and fluorouracil (CMF) versus CMF plus fluoxymesterone (CMFH) maintenance therapies in responders to 6 months of induction therapy which consisted of either CMF, CMF plus prednisone (CMFP), or adriamycin plus vincristine (AV). Following the maintenance randomization 12% of the patients converted from a PR to a CR status. The median time from randomization to treatment failure was 9.5 months for CMFH and 6.7 months for CMF (p = 0.03). This difference was observed only for partial responders (p = 0.01) and not for complete responders. Patients receiving CMFH tended to maintain higher hemoglobin, leukocyte, and platelet levels, and receive a higher dosage of each of the cytotoxic drugs. The results are taken as evidence that the addition of fluoxymesterone to a maintenance CMF regimen provides a therapeutic advantage. It is hypothesized that this effect is due at least in part to fluoxymesterone associated maintenance of improved marrow function resulting in greater myelosuppressive drug delivery.

Aged↗
PubMed1981

Prolonged cryopreservation of human bone marrow.

We tested the viability of human bone marrow stored for 40 to 42 months in the vapor phase of liquid nitrogen. A median of 2 X 10(10) nucleated cells obtained from eight patients were concentrated to 1.3 X 10(10) using discontinuous centrifugation. These were stored in polyolefin bags in volumes of 100 to 500 ml using 10% dimethyl sulfoxide (DMSO) as cryoprotectant. Cell number and granulocyte - monocyte colony - forming cell (CFU-c) plating efficiency were determined before freezing and after thawing, after dilution and removal of DMSO, and after 2 to 4 hr of additional incubation. The median difference in cell number and CFU-c plating efficiency after this prolonged storage was -9 and +2%, respectively. Dilution, washing, and a 2-hr incubation were associated with cell losses of 24, 24, and 19% and increases in CFU-c plating efficiency, ranging from 22 to 79%. The number of viable CFU-c was never significantly lower than the number of CFU-c stored or initially thawed. Vapor phase storage appears to be adequate for prolonged human bone marrow cryopreservation using CFU-c viability as a determinant.

Adult↗
PubMed1981

Prolonged disease-free survival in advanced breast cancer treated with "super-CMF" adriamycin: an alternating regimen employing high-dose methotrexate with citrovorum factor rescue.

Sixty-six patients were treated with the combination "super-CMF" as follows: cyclophosphamide 100 mg/m2 po days 2 through 14; methotrexate 3.0 g/m2 iv days 1 and 8; 5-fluorouracil 600 m g/m2 iv days 1 and 8; citrovorum factor rescue 10 mg/m2 iv days 2 and 9 and po days 2 through 4 and 9 through 11; and Adriamycin 70 to 90 mg/m2 iv day 29. This cycle was repeated at 49-day intervals. The single-agent activity of high-dose methotrexate with rescue was first evaluated in breast cancer patients in a truncated phase II study; 3 of 19 had a partial response (greater than 50% regression of measurable lesions) after 2 to 6 weekly courses and another 6 to 19 had some objective evidence of response (greater than 25%, less than 50%). The response rate to the combination "super-CMF" was: complete response (CR) 15 of 55 evaluable patients (27%) and partial response (PR) 28 of 55 (51%). The median duration of response was 24.5 months and the median time to treatment failure was 21.6 months. Nineteen of these patients have completed 12 to 18 months of drug treatment and have been followed in continuing remission for 1 to 28 months without further therapy. The total response rate and the CR rate achieved with this regimen are substantial, and the durability of the responses appears to be considerably greater than that obtained with other drug combinations.

Adult↗
PubMed1981

Adriamycin plus vincristine alone or with dibromodulcitol or ICRF-159 in metastatic breast cancer.

A total of 268 patients with metastatic breast cancer were prospectively randomized to receive Adriamycin-vincristine (AV) alone, AV plus dibromodulcitol (AVD), or AV plus ICRF-159 (AVI). Two hundred thirty were eligible and had received prior chemotherapy. The objective response rates were 27%, 23%, and 16% for AV, AVD and AVI, respectively, and an additional 44% had stabilization of disease. Duration of responses ranged from 4.1 to 4.6 months and the times to treatment failure from 2.9 to 3.8 months. Median survivals ranged from 7.1 to 8.3 months. Performance status and the presence of liver or brain metastases were significant prognostic variables for outcome. These studies show that AVI is inferior to AV with respect to survival when prognostic variables are taken into account in a multivariate model, whereas AVD which utilizes a lower dose of Adriamycin appears to have comparable antitumor activity to AV. This does not appear to offer any benefit to patients previously treated with chemotherapy, as in this trial, but it may be an advantage to previously untreated patients since Adriamycin can be administered to responding patients over a longer period of time before an unacceptable total cumulative dose is reached.

Aged↗
PubMed1980

Combination chemotherapy with adriamycin-cyclophosphamide for advanced ovarian carcinoma.

Combination chemotherapy with Adriamycin-cyclophosphamide was employed after surgical treatment in 60 women with Stage III-IV ovarian adenocarcinoma. Of 53 evaluable patients, objective response was noted in 34 of 41 (83%) without prior cytotoxic therapy but in only two of 12 (17%) who had failed a single alkylating agent or radiotherapy (P < .005). Complete response was confirmed by a negative biopsy at the site(s) of prior disease in 12 patients. Eleven of the 12 biopsy-confirmed complete responses were achieved in patients without pretreatment palpable tumor. Twenty-four out of 41 patients with palpable masses responded but only one was confirmed as complete. Confirmed complete responses had a median duration of 24 months, whereas the median duration of all other responses was only seven months. The median survival for patients in whom Adriamycin-cyclophosphamide was the initial chemotherapy was 24 months. The median survival in patients with palpable tumor exceeds that of historical controls matched for age, tumor cell type, and grade (P = .05); the median survival for the confirmed complete responders has not been reached. The toxicity of this regimen was acceptable at doses of Adriamycin and cyclophosphamide of 45 mg and 500 mg/M2 body surface area, respectively. Extensive excision of tumor followed by effective combination chemotherapy offers the best current approach toward improved patient survival in advanced ovarian cancer.

Adenocarcinoma↗
PubMed1980

Preschoolers' understanding of simple object transformations.

The ability of 3- and 4-year-old children to reason about the components of event sequences involving simple transformations was tested in 2 experiments. In Experient I children saw picture "stories" of the form object, instrument, and transformed object, with 1 item deleted. They filled in the missing position from 3 choice cards. Children in both groups correctly filled in all positions and therefore could: (1) predict the transformed state of an object, (2) retrieve the initial state of an object, and (3) understand the implicit actions that mediate 2 object states. This was true for transformations that (1) either altered or restored an object, and (2) represented familiar or unusual events. In Experiment II only the instrument item was deleted. Children demonstrated an ability to represent reciprocal transformations (e.g., break-fix); they chose the 2 of 4 instruments that altered and restored the same object. The younger children were less able to describe the events and found it somewhat easier to reason about transformations that altered objects.

Child, Preschool↗