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Biomedical subjects

J R Durant

Publications and source records attributed to J R Durant.

At least 37 records · Page 2Linked to original sources
PubMed1983

Hormonal therapy of gynecologic cancers.

Progestins produce objective responses in about 30% of unselected patients with metastatic adenocarcinoma of the uterus. Selection of patients for treatment based on the presence of progesterone receptors may increase the probability of a response. There is little evidence to support a role of hormones as adjuvants in the primary management of poor-risk patients or in combination with chemotherapy. Antiestrogens may have a role as secondary agents in adenocarcinoma of the uterus, and progestins may have a role as secondary agents in ovarian cancer.

Adenocarcinoma↗
PubMed1983

Tumor proliferation and chemotherapy in immunosuppressed mice.

The influences on host immunosuppression by treatment with cyclophosphamide (200 mg/kg), steroid (prednisolone, 12.0 mg/kg for seven doses or 235 mg/kg for one dose), and adult thymectomy on tumor growth were compared. Treatment with cyclophosphamide 24 hr prior to MOPC 104E tumor transplantation produced the greatest facilitation of tumor growth. The role of prednisolone in rendering the MOPC 104E cells more vulnerable to conventional chemotherapy was also investigated. The combination of prednisolone with melphalan added measurably to the cytotoxicity of the treatment and increased the percentage of disease-free survivors. The observed effects of prednisolone might have been due to the increase in the cycling of myeloma cells directly, or the drug may have facilitated growth of the myeloma by blocking host expansion of T-cell immunity. Alterations of the host by adult thymectomy and immunosuppression with cyclophosphamide or prednisolone led to growth facilitation of myeloma. The limited studies reported here point out the usefulness of facilitation of tumor growth to accomplish increased neoplastic cell kill and increased percentage of disease-free survivors.

Animals↗
PubMed1982

A randomized prospective clinical trial of adjuvant C. parvum immunotherapy in 260 patients with clinically localized melanoma (Stage I): prognostic factors analysis and preliminary results of immunotherapy.

A total of 260 patients with clinically localized melanoma (Stage I) from 18 medical institutions in the Southeastern Cancer Study Group were randomized to receive either surgical treatment alone, or surgery plus Corynebacterium parvum immunotherapy. A multivariant analysis (Cox regression model) of nine prognostic factors was performed on 110 patients with a minimum of two years follow-up. The dominant prognostic variables were thickness (P = 0.0007) and anatomic location of the melanoma (trunk versus other, P = 0.015). Disease-free survival curves were then calculated for 204 surgically evaluable patients. Overall, there was no significant difference in three-year survival for the two-treatment arms, which was 81% for the adjuvant immunotherapy group compared to 67% for the surgical control group (P = 0.10). The median follow-up period was 24 months (range, 1-60 months). However, when the data was subgrouped by tumor thickness, an apparent benefit of immunotherapy was observed in 49 patients with melanomas greater than 3 mm in thickness. Only five of 23 such patients relapsed after receiving C. parvum. Their three-year disease-free survival was 73%. In contrast, 13 of 26 patients who did not receive immunotherapy have relapsed so far and their three-year disease-free survival was only 33% (P = 0.01). In the 175 patients with melanomas less than 3 mm in thickness, both treatment arms had identical three-year disease-free survival rates of 83%. No significant differences between the treatment arms were observed using other prognostic variables, including the level of invasion. Toxicity to C. parvum injections was minimal in most patients. It is concluded that a prognostic factor analysis is critically important in adjunctive trials of melanoma to determine which dominant variables should be used for analyzing patient subgroups; that C. parvum immunotherapy appears to be associated with an improved disease-free survival rate in the subgroup of patients with melanomas greater than 3 mm thickness (this early encouraging data must still be confirmed with continued patients accrual and a longer observation period); and that patients with melanomas less than 3 mm thickness have a relatively favorable prognosis after appropriate surgical treatment, and immunotherapy does not improve their survival rates.

Adolescent↗
PubMed1982

Inflammatory fibrous histiocytoma: an important variant of malignant fibrous histiocytoma highly responsive to chemotherapy.

Inflammatory fibrous histiocytoma is a recently recognized variant of malignant fibrous histiocytoma. Patients managed with surgical excision or radiation therapy usually have had multiple recurrences, often with metastases. The disease is insidious but ultimately fatal. Four consecutive patients were treated with inflammatory fibrous histiocytoma with alkylating agents with or without anthracyclines and produced prolonged and sustained remissions. Inflammatory fibrous histiocytoma may be another highly chemotherapeutically responsive tumor that deserves active case identification for aggressive curative therapy.

Adolescent↗
PubMed1982

Chemotherapy for advanced Hodgkin's disease: conclusions from the Southeastern Cancer Study Group.

The Southeastern Cancer Study Group has explored a variety of approaches to the management of advanced Hodgkin's disease. These have largely involved the use of nitrosoureas, especially BCNU (carmustine), alone or in combination with other agents. Initial phase II trials of BCNU as a single agent in patients refractory to mechlorethamine demonstrated considerable antitumor activity. Exploratory experiments with BCNU in combination with alkylating agents, vinca alkaloids, and corticosteroids resulted in the development of the combination BVCPP (BCNU, vinblastine, cyclophosphamide, procarbazine, and prednisone). BVCPP, given only once monthly, produces at least a 65% complete response rate with minimal to moderate toxicity, making it an effective alternative to other regimens such as MOPP. Alternating BVCPP with a non-cross-resistant combination (doxorubicin, DTIc [dacarbazine], and bleomycin) offered no advantage in response rate or survival. Continued research with new agents and/or combined modality approaches is necessary in view of continued primary and secondary treatment failure with all regimens used for the management of advanced Hodgkin's disease.

Antineoplastic Agents↗
PubMed1981

Subcategories of histiocytic lymphoma: associations with survival and reproducibility of classification. The Southeastern Cancer Study Group experience.

Five pathologists reviewed histologic slides from 134 cases of histiocytic lymphoma and subclassified these cases using Lukes-Collins classification system. Of 98 morphologically subclassifiable cases, 85 were distributed among three categories, each presumed to represent a lymphoma of follicular center cell origin. The remaining 12 cases were classified among three additional categories. The cases within the three follicular center cell categories, considered collectively, had a significantly better survival than did the cases within the other three categories considered as a whole. The pathologists classified cases generally as being of a follicular center cell type with a high degree of reproducibility, but their individual classifications varied significantly with respect to more specific morphologic categories. Suboptimal quality of histologic sections was a significant factor contributing to problems in morphologic classification. Ancillary immunologic techniques may be required for definitive subclassification of large cell lymphomas.

Adolescent↗
PubMed1981

Evidence that estrogen-receptor-negative, progesterone-receptor-positive breast and ovarian carcinomas contain estrogen receptor.

A small number of primary metastatic breast carcinomas are estrogen-receptor-negative and progesterone-receptor-positive (ER-, PGR+) under the normal ligand-binding assay or sucrose density gradient conditions. Among more than 500 tumors analyzed in this laboratory over a year and a half, 28 cases fit this category, 18 of which were patients 51 years of age or younger (Group A) and 7 were patients over the age of 56 (Group B), The ages of three patients were unknown (Group C). By treatment of each of those tumor cytosols with dextran-coated charcoal before the assay was done, 13 of group A became positive (ER range 10-87 fmol/mg protein); 1 was borderline (ER 3-9 fmol/mg protein); 1 became positive only on sucrose gradient determination, and 2 remained negative. In comparison, two patients in group B shifted from borderline ER to ER+ and only one ER- became ER+ at 10 fmol/mg protein. The data provide additional rationale for determining both ER and PGR in all patients, and have obvious implications for the need of standard methods of determining ER and PGR in the prognosis of women with breast cancer.

Adult↗
PubMed1981

Thoracic and elective brain irradiation with concomitant or delayed multiagent chemotherapy in the treatment of localized small cell carcinoma of the lung: a randomized prospective study by the Southeastern Cancer Study Group.

A prospective randomized study was carried out to compare the effectiveness of concomitant or delayed multiagent chemotherapy combined with irradiation to the primary tumor and regional lymph nodes and to the brain in a group of 70 patients with histologically proven small cell undifferentiated carcinoma of the lung. Complete and partial response in both groups was comparable, and the overall survival was comparable. However, relapse-free survival was significantly higher in patients receiving concomitant chemotherapy and irradiation in comparison with the radiotherapy alone group. Disease-free survival was higher in the concomitant chemotherapy-radiotherapy patients, although survival was not significantly modified, probably because of suboptimal chemotherapy. The initial intrathoracic failure rate was 40.7% inthe concomitant chemotherapy-irradiation group, compared with 53.8% in the radiotherapy-alone patients. None of the patients receiving delayed chemotherapy following the radiotherapy recurrence showed significant tumor response to the drugs. The incidence of distant metastasis was slightly lower in the chemotherapy groups. Brain metastases were noted in 7% of the patients in both groups. Increased intrathoracic recurrences were noted in patients with lower doses of irradiation. Nine of 13 patients treated with inadequate portals developed intrathoracic recurrences in comparison to 13 of 40 treated with adequate irradiation fields. The study emphasizes the need for intensive chemotherapy and adequate radiation therapy to improve survival of patients with small cell undifferentiated carcinoma of the lung. Additional trials are necessary to assess the role of each modality in the management of these patients.

Aged↗
PubMed1981

Importance of stratification in later stages of clinical trials.

An erroneous assumption is often made in clinical trials that once patients achieve a remission on an early phase of a study, then they can be randomized to various arms of later phases of that trial without stratifying for induction therapy, the contention being that complete remissions imply a homogeneous sample with respect to therapy already received. This short article shows that this is not the case because induction therapies may be equal with respect to the percentage of complete remissions achieved but may differ in overall proportion of patients actually cured. Examples of clinical trials with this flaw are presented. A statistical explanation of the problem, which illustrates specific methodological points, is included.

Animals↗