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Biomedical subjects

D C Tormey

Publications and source records attributed to D C Tormey.

At least 127 records · Page 7Linked to original sources
PubMed1982

A pilot study of mitomycin-C and tamoxifen (MT) versus dibromodulcitol, adriamycin, and tamoxifen (DAT).

The aim of this study was to compare the treatment efficacy of mitomycin-C plus tamoxifen (MT) to adriamycin, dibromodulcitol and tamoxifen (DAT) in previously treated patients with metastatic breast cancer. Thirty-two patients with measurable or evaluable disease were entered on the study. Twenty-three were prospectively randomized to receive DAT (Group 1) or MT (Group 2). Nine patients with prior exposure to adriamycin were directly assigned to receive MT (Group 3). Thirty-one patients were evaluable for response and toxicity. The hematological toxicities were comparable among the three treatment groups. DAT gave more nausea and vomiting than MT. One patient developed irreversible fatal congestive heart failure while receiving DAT. The response for Group 1 was 5/11, Group 2, 3/12, and Group 3, 3/8. The duration of response for patients in Group 1 was 455+, 315, 251, 239, 231 days, in Group 2 it was 328+, 144+, 119, and in Group 3 it was 35+, 84, and 112 days. The median time to treatment failure did not differ significantly between Group 1 (114 days), 2 (83 days) and 3 (61 days) (p = 0.24). The median survival time was similar among the three groups (p = 0.41). This pilot study suggests that MT and DAT are both effective treatment programs in patients with metastatic breast cancer who have failed prior chemotherapy regimens.

Antibiotics, Antineoplastic↗
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

Clinical studies of a fast homoarginine-sensitive alkaline phosphatase in patients with cancer.

The activity of an isoenzyme of alkaline phosphatase (FHAP) was measured in serum samples obtained from 1692 individual subjects. The median FHAP concentration in patients with untreated or recurrent cancer (2.73 IU/liter) was two-fold higher than in hospitalized control patients with illnesses other than cancer (1.17 IU/liter) and three-fold higher than in healthy control subjects (0.93 IU/liter). Among patients with either breast or colorectal cancer who were clinically disease free following their initial therapy, the median FHAP concentration (1.54 IU/liter) was intermediate between the median FHAP concentration in patients with untreated or recurrent cancer and that of healthy control subjects. In order to illustrate the potential clinical application of FHAP as a diagnostic cancer marker, we have selected a serum FHAP concentration of 2.22 IU/liter as a reference value above which only 3% of healthy control subjects would have a "positive" test. Utilizing this reference value, 58% of the patients in the present study with untreated or recurrent cancer would have a positive FHAP test, whereas only 11%, of hospitalized patients with illnesses other than cancer would have a positive test. These data suggest that FHAP may be equivalent to the carcinoembryonic antigen as a diagnostic cancer marker.

Adult↗
PubMed1981

Phase I--II evaluation of combination cyclophosphamide, 5-fluorouracil, hexamethylmelamine, and prednisone in advanced breast cancer.

A four-drug combination of intermittent high-dose cyclophosphamide with 5-fluorouracil, hexamethylmelamine, and prednisone was given to 19 patients with advanced breast cancer. Objective response was documented in 7 of 18 evaluable patients. The median duration of response was 99 days. Response was observed in 6/7 patients without visceral disease and 1/11 patients with visceral disease. Toxicity was acceptable and no life-threatening toxicity was observed. Three patients have received the four-drug combination for more than 1 year without serious side effects. This regimen may serve as an alternative treatment for patients without visceral metastasis who have failed to respond to other combination chemotherapy regimens.

Adenocarcinoma↗
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↗
PubMed1981

Relationship between time to treatment failure and survival and between time to response and response duration in metastatic breast cancer. Implications for treatment.

The hypothesis that longer times to response (TTR) and times to treatment failure (TTF) are associated with a more chronic disease resulting in progressively longer response durations (TRTF) and times from treatment failure to death (TFTD) was evaluated in metastatic breast carcinoma. Data from 553 patients across two similar Eastern Cooperative Group combination chemotherapy trials was utilized to evaluate the relationship between TTR and TRTF, and TTF and TFTD. The TTR did not appear to predict for TRTF, which was approximately 7.6 months irrespective of TTR durations from 1 to 6+ months. The TFTD increased to approximately 8 months as the TTF increased to 6 months; thereafter, the TFTD remained stable up to at least 17 months of TTF. The discordance in the results of the two analyses suggests that the operational hypothesis is not necessarily true. However, these data, along with the subset analyses and previous animal and human studies, were taken as evidence that ultimate survival is selected by the response to the first regimen employed, that the primary therapeutic impact of a regimen is in the first 3-6 months, and that the regimen should maximize therapy early to achieve rapid complete remissions.

Adult↗
PubMed1981

Vindesine. A phase II trial in advanced breast cancer patients.

A phase II trial of vindesine (VDS), a new vinca alkaloid, has been carried out in 40 patients with metastatic breast cancer. Patients entered in the study had been previously treated with an average of two chemotherapy regimens. Treatment was given as a weekly I.V. bolus of VDS at 3 mg/m2. The response rate in 31 evaluable patients was 19%, i.e., one complete response (CR), four partial responses, and one improvement in osseous disease (IMP). In 36 patients evaluable for toxicity, neurological and hematological toxicity was most significant. Half the patients treated had received previous vincristine therapy; this factor did not appear significant with regard to toxicity or response to VDS.

Adult↗
PubMed1981

Phase II study of dibromodulcitol in colorectal, kidney, and other carcinomas.

In a phase II study dibromodulcitol (DBD), an alpha-omega dibrominated hexitol, was used to treat 99 previously treated patients with colon, rectal, kidney, and other tumors. Six patients were ineligible and 10 patients were nonevaluable for response. Aside from thrombocytopenia toxicity was moderate. Twenty-three patients had platelet nadirs of less than 50,000/mm3 and there were three thrombocytopenic-associated drug deaths. One of 21 rectal and 1 of 13 kidney cancer patients entered a remission. All but seven patients had received previous treatment with one or more cytotoxic agents. Previously treated patients with colorectal and kidney cancer appear to be resistant to DBD.

Aged↗
PubMed1980

Biologic markers in breast carcinoma: clinical correlations with urinary polyamines.

Urinary polyamine levels were evaluated in patients with breast carcinoma. The individual levels of putrescine, spermidine, spermine, and cadaverine, and the product/precursor levels of putrescine, spermidine, and spermine were analyzed. Elevations of one or more individual polyamines or of the ratios were found in 50% of patients with metastatic disease, 38.5% of preoperative patients, and 35.7% of 5--24 week postoperative N + patients. Sequential sampling of patients with metastatic disease suggested that changes in elevated polyamine levels tend to reflect the clinical course of the disease, especially for the association of treatment failure with rising elevated values. The presence of one or more elevated parameters prior to treatment of metastatic disease tended to be associated with a higher response rate (85.7 vs. 68.4%) than all normal levels. Five of nine patients who recurred postoperatively had preceding postoperative polyamine elevations. In addition, there was a trend for a shorter disease-free time among patients with one of more elevated polyamine parameters between 5--24 weeks postoperatively than among patients with normal parameters. These data suggest that measurement of urinary polyamine levels, including calculation of the product/precursor levels, may be a useful clinical adjunct in the management of patients with breast carcinoma.

Breast Neoplasms↗
PubMed1980

Biological markers in breast carcinoma--clinical correlations with pseudouridine, N2,N2-dimethylguanosine, and 1-methylinosine.

Urinary levels of the minor nucleosides, pseudouridine (psi),N2, N2-dimethylguanosine (m22G), and 1-methylinosine (m1I), were investigated in patients with breast carcinoma. Elevated levels of psi were observed in 27/131 (20.6%) patients with metastatic disease, 1/14 (7.1%) preoperative patients, and 1/28 (3.6%) postoperative N+ patients. Elevated levels of m22G and M1I were observed, respectively, in 46/131 (35.1%) and 274131 (20.6%) patients with metastatic disease, 3/14 (21.4%) and 3/14 preoperative patients, and 6/28 (21.4%) and 2/28 (7.1%) postoperative N+ patients. There was no correlation between nucleoside levels and involvement of specific organ sites with metastatic disease, nor with chemotherapy response rate or time to treatment failure. During the treatment of metastatic disease there was a tendency for elevated pretherapy psi levels to decrease with attainment of a response and, if the levels subsequently rose to be associated with treatment failure. However, increasing levels of m22G and 71I occurred with both response and disease progression. These results suggest that routine measurement of the level of the urinary nucleosides would be of limited value for following the disease course in patients with breast cancer.

Antineoplastic Agents↗
PubMed1980

Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group.

The prognostic effect of weight loss prior to chemotherapy was analyzed using data from 3,047 patients enrolled in 12 chemotherapy protocols of the Eastern Cooperative Oncology Group. The frequency of weight loss ranged from 31 percent for favorable non-Hodgkin's lymphoma to 87 percent in gastric cancer. Median survival was significantly shorter in nine protocols for the patients with weight loss compared to the patients with no weight loss. Chemotherapy response rates were lower in the patients with weight loss, but only in patients with breast cancer was this difference significant. Decreasing weight was correlated with decreasing performance status except for patients with pancreatic and gastric cancer. Within performance status categories, weight loss was associated with decreased median survival. The frequency of weight loss increased with increasing number of anatomic sites involved with metastases, but within categories of anatomic involvement, weight loss was associated with decreased median survival. These observations emphasize the prognostic effect of weight loss, especially in patients with a favorable performance status or a limited anatomic involvement with tumor.

Activities of Daily Living↗
PubMed1979

Malignant mesothelioma presenting in the pleura and peritoneum.

Malignant mesothelioma presenting in the pleura and peritoneum is described in a middle-aged man. The patient lacked significant asbestos exposure which is not unexpected from both the clinical literature and animal inhalation tumor data. Computerized axial tomographic correlation is provided. Partial remission was achieved with the administration of adriamycin and DTIC.

Adult↗
PubMed1979

Dibromodulcitol.

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Animals↗
PubMed1979

Effects of steroid hormones on phytohemagglutinin-stimulated human peripheral blood lymphocytes.

The interactions of steroid hormones and human peripheral blood lymphocytes (PBLs) have been investigated following glass-wool column separation of PBLs and incubation in a serum-free medium in the presence of phytohemagglutinin (PHA). Addition of hydrocortisone or progesterone above physiological concentrations resulted in inhibition of [14C]2-TdR incorporation. 17beta-Estradiol and 5alpha-dihydrotestosterone inhibited [14C]2-TdR incorporation only at steroid concentrations thousands of times higher than the physiological concentrations. The kinetics of hydrocortisone and progesterone inhibition appeared to be similar and suggested that events occurring early after PHA addition were most sensitive to steroid inhibition and that addition of steroid at 28 hr, at the end of the early prereplicative phase of the cell cycle, inhibited DNA synthesis only at very high concentrations. The PHA-induced increase in RNA synthesis could be prevented by hydrocortisone addition even if delayed for up to 4 hr; morphological transformation was similarly affected. These data, and other investigations showing that progesterone binds to a specific glucocorticoid receptor in PBLs suggest that the progesterone inhibition of macromolecular synthesis in human PBLs is exerted via a glucocorticoid-like mechanism, and that glucocorticoid sensitivity is greatest during the early phases of lymphocyte activation. These results also provide a rationale for the apparent in vivo immunosuppressive capability of progesterone.

Cell Division↗
PubMed1978

Synovial sarcoma of the neck associated with previous head and neck radiation therapy.

Synovial sarcoma is a rare neoplasm that uncommonly arises in the neck. Fourteen years after facial and neck radiation therapy for acne, synovial sarcoma of the neck developed in a young man. Possible radiation-induced benign and malignant neoplasms that arise in the head and neck region, either of thyroid or extrathyroid origin, remain a continuing medical problem.

Acne Vulgaris↗
PubMed1978

The bone marrow examination in breast cancer: diagnostic considerations and clinical usefulness.

Bone marrow examinations were performed on 116 women with primary and metastatic breast cancer and were correlated with the clinical status of the patient and other specific diagnostic modalities. The relative diagnostic efficacy of the marrow biopsy, aspirate smear and clot section was examined, as was the value of serial marrow examinations. A marrow positive for tumor was found in 40% of those with metastatic disease, 55% with positive x-rays, 56% with positive bone scans, but only 4% (1/24) with both scan and x-ray normal. Routine hematologic parameters were of limited usefulness in predicting the finding of a positive marrow. The biopsy was superior to the smear and clot section but aspirated material also had to be analyzed to maximize diagnostic yield. When analyzed qualitatively, i.e., positive or negative for tumor, serial marrow examinations were not useful in assessing the efficacy of antitumor treatment. The potential usefulness of bone marrow examination in patients with breast cancer is discussed.

Biopsy, Needle↗