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Biomedical subjects

J F Foley

Publications and source records attributed to J F Foley.

At least 55 records · Page 3Linked to original sources
PubMed1991

Improving accrual into cancer clinical trials.

It is thought by some that there are inadequate patient entries on high priority national cancer treatment protocols, resulting in intolerable delays in addressing crucial research issues. The North Central Cancer Treatment Group in Rochester, Minnesota generated a questionnaire with possible impediments to patient treatment entry as well as suggested measures for approving accrual. Of 334 questionnaires, 63% were completed and returned by medical oncologists, radiation therapists, surgeons and nurse/data managers. The most frequently listed impediments included patients' advanced age or fragility, inadequate health insurance, and excess travel distance. Protocol concerns included too many tests that were too complex and too costly. Practice concerns included physicians too busy and inadequate help. Suggestions toward improving patient accrual included subsidizing drugs, subsidizing nonessential tests for patient care, and increasing funding for support personnel. Popular suggestions for education efforts included teaching the importance of clinical trials, emphasizing personal benefit to the patient and recognition of physicians and institutions participating. It was felt that protocols should be simplified, be more consistent with practice, and be more flexible. These considerations are relevant not only in the interests of more effective clinical research but also in the interests of appropriate education of residents and oncology fellows involved in clinical trials.

Clinical Protocols↗
PubMed1990

Dose-response relationship between O6-methylguanine formation in Clara cells and induction of pulmonary neoplasia in the rat by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

The relationship between the formation of O6-methylguanine (O6MG) and the induction of lung, liver, and nasal tumors in the Fisher 344 rat by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was examined in a dose-response study. Animals were treated for 20 wk (3 times/wk) with concentrations of NNK ranging from 0.03 to 50 mg/kg to induce tumors. Steady-state concentrations of O6MG were quantitated, and cytotoxicity was assessed in target cells and tissues after 4 wk of treatment with NNK. No cytotoxicity was detected in the lung during treatment with NNK. The formation of O6MG was greatest in Clara cells compared with macrophages, type II cells, small cells, and whole lung at all doses examined. The difference in adduct concentration between the Clara cell and other pulmonary cell types was most pronounced with low doses of carcinogen. The O6MG:dose ratio, an index of alkylation efficiency, increased 29-fold as the dose of NNK was decreased from 50 to 1 mg/kg of carcinogen. In contrast, only a small increase in alkylation efficiency was observed in type II cells and whole lung. A significant number of tumors were induced in the lung at doses of 0.1 to 50 mg/kg with incidences ranging from 10% at the lowest dose up to 87% in the group of animals which received 50 mg/kg of NNK. A linear relationship was observed when the concentration of O6MG in Clara cells as a function of dose was plotted against the corresponding tumor incidence. This relationship was not observed using DNA adduct concentrations in type II cells or whole lung. The development of pulmonary tumors appeared to involve the formation of alveolar hyperplasias which progressed to adenomas and finally to carcinomas. The majority of adenomas were solid, whereas carcinomas were mainly papillary. Examination of the ultrastructure of the hyperplasias, adenomas, and carcinomas revealed morphological structures (e.g., lamellar bodies, tubular myelin) which are associated with type II cells. Thus, these data suggest that the majority of neoplasms in the lung begin as type II cell proliferations with progression to adenomas and carcinomas within the areas of hyperplasia. The lack of agreement between biochemical and morphological findings makes it difficult to hypothesize a cell of origin for the pulmonary neoplasms. In contrast to the lung, tumors were induced in the liver and nasal passages only after exposure to high doses of NNK. Moreover, both the formation of DNA adducts and cytotoxicity appear obligatory for the generation of tumors in these tissues.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

A phase III trial on the therapy of advanced pancreatic carcinoma. Evaluations of the Mallinson regimen and combined 5-fluorouracil, doxorubicin, and cisplatin.

One hundred eighty-seven patients with histologically proven advanced pancreatic adenocarcinoma were randomly assigned to therapy with 5-fluorouracil (5-FU) alone, to the Mallinson regimen (combined and sequential 5-FU, cyclophosphamide, methotrexate, vincristine, and mitomycin C), or to combined 5-FU, doxorubicin, and cisplatin (FAP). Patients with both measurable and nonmeasurable disease were included and the primary study end point was survival. Among 41 patients with measurable disease, objective response rates were 7% for 5-FU alone, 21% for the Mallinson regimen, and 15% for FAP. The median interval to progression for each of the three regimens was 2.5 months. Survival curves intertwined with the median survival times for 5-FU alone and the Mallinson regimen at 4.5 months and for FAP at 3.5 months. Compared with 5-FU alone, both the Mallinson regimen and FAP produced significantly more toxicity. Neither the Mallinson regimen nor FAP can be recommended as therapy for advanced pancreatic carcinoma. Any chemotherapy for this disease should remain an experimental endeavor.

Adenocarcinoma↗
PubMed1989

Randomized trial to evaluate the addition of tamoxifen to cyclophosphamide, 5-fluorouracil, prednisone adjuvant therapy in premenopausal women with node-positive breast cancer.

A randomized clinical trial was performed to determine if the addition of hormonal therapy with tamoxifen to a combination chemotherapy regimen was superior to the chemotherapy alone for adjuvant treatment of premenopausal women after mastectomy for node-positive breast cancer. The chemotherapy regimen utilized consisted of cyclophosphamide (C), 5-fluorouracil (F), and prednisone (P), and the doses employed were: C, 150 mg/m2 IV days 1 to 5; F, 300 mg/m2 IV days 1 to 5; and P, 10 mg orally three times daily on days 1 to 7. A total of ten courses of therapy, given every 6 weeks, was planned. Tamoxifen (T) was given at a dose of 10 mg twice daily and was stopped 6 weeks after the last course of CFP. Four hundred patients are fully eligible and evaluable. With a median observation time of 5.3 years, the proportion of recurrences on each arm were: CFP, 95 of 202 (47%); CFPT, 77 of 198 (39%). The relapse-free survival distribution for CFPT was superior to that for CFP, at a borderline level of significance (two-sided P = 0.06). When significant prognostic factors were considered in covariate analysis, CFPT was not significantly better than CFP (P = 0.43). This marked change in level was due to imbalance in several factors not considered in stratification. Currently, 31% of CFP and 25% of CFPT patients have died, and although there is a slight separation of the survival curves in favor of CFPT, the difference is not significant (P = 0.21). Analysis within receptor subsets also showed no significant advantage for the addition of tamoxifen. This study does not establish a significant advantage for the concurrent administration of tamoxifen with the CFP regimen. It does, however, clearly demonstrate the importance of examination of clinically important prognostic factors, even those not utilized in stratification, and consideration of these factors in covariate analysis if imbalances are present.

Adult↗
PubMed1989

Randomized trial of doxorubicin alone or combined with vincristine and mitomycin C in women with metastatic breast cancer.

A randomized clinical trial was performed to determine if combination therapy with doxorubicin, vincristine, and mitomycin C (DVM) was superior to doxorubicin alone in women with metastatic breast cancer for whom prior chemotherapy had failed. A total of 185 women were randomized to monthly courses of D (60 mg/m2, observation after 500 mg/m2); or D (50 mg/m2, maximum cumulative dose 500 mg/m2), V (1 mg/m2), and M (10 mg/m2, given every other cycle). Patients failing after D alone could receive V (1 mg weekly for 5 weeks, then 1.2 mg/m2 every 5 weeks) plus M (12 mg/m2 every 5 weeks). Objective responses were seen in 24 of 95 patients (25%) on D alone and 39 of 90 patients (43%) on DVM (two-sided p = 0.01). The time to disease progression distribution was significantly better for DVM (two-sided p = 0.02), but the magnitude of the advantage was small with the medians being 2.7 months for D and 4.2 months for DVM. There was no significant difference in survival between the two regimens. The degree of leukopenia was greater for DVM both in terms of median white blood cell nadir (1,300/microL versus 1,700/microL) and percentage of patients with a nadir less than 1,000/microL (33% versus 16%). A total of 45 patients received VM following D alone, and only seven (16%) achieved an objective response. We conclude that, despite a significantly higher response rate and longer time to progression, the degree of clinical benefit is not sufficient to recommend the combination of DVM over D alone as second-line therapy for women with metastatic breast cancer. The level of efficacy seen with VM as tertiary therapy is low and is of such a magnitude to suggest that V adds little but toxicity to M.

Adult↗
PubMed1988

Blood histamine and solid malignant tumors.

A clinical study was performed to determine whether patients with a newly diagnosed solid malignant tumor manifest an alteration in whole-blood histamine levels. Our results indicate that such patients have blood histamine nearly three times greater than either normal, healthy individuals or noncancerous disease controls. Following surgical removal of the tumor, blood histamine levels remained high for 2 months and then dropped close to the normal range 3 months after surgery. Basophil counts did not change significantly in the presence of a malignant tumor. Patients receiving either chemotherapy or radiation therapy, and terminal cancer patients who were no longer receiving any therapy except for pain control had blood histamine within or below the normal range. By analogy with animals studies, we suggest that nascent histamine synthesis is increased in the presence of a developing tumor. The clinical usefullness of this observation remains to be determined.

Basophils↗
PubMed1988

A factor produced by human cells in vitro that changes HeLa cell colonial morphology.

Colonies of HeLa cells cultured in media supplemented with human or bovine serum or both can be morphologically described as three types: diffuse, intermediate, and compact, with their modal distribution depending on the serum or sera added to the growth medium. We have observed that for a particular medium or serum system, the percentage of compact colonies remains fairly constant under normal culture conditions, 0.2%, whereas the diffuse and intermediate colonies vary over a much wider range. The presence of certain substances as trypsin, heparin and Darvan in the medium favor the increase of compact colonies at the expense of other types. Furthermore, we have discovered that colonial morphology is influenced by cocultivation of the HeLa cells with human fibroblastlike cells, the compact colonies increasing as the density of the fibroblast element introduced into the mixed cultures is increased. Subsequent investigation revealed that conditioned medium from confluent fibroblast and HeLa cell cultures contained a factor(s), that significantly increased the percentage of compact colonies. The factor is nondialyzable, heat-stable and can be neutralized by serum. Recorded in this presentation are preliminary observations on the kinetics of colony formation and the interaction among the three HeLa cell colony types, the diffuse, the intermediate, and the compact. The factor's effect on HeLa cell colonial morphology is time dependent and rapidly reversed if the factor(s) is removed and fresh medium added.

Biological Factors↗
PubMed1988

Breast cancer examination experience of medical students and residents.

A survey of fourth-year medical students and residents at three institutions revealed a low experience in examining patients with primary breast cancer. Although the experience was low, there was high confidence in their ability to examine the breast. Changes in learning experiences are necessary.

Breast Neoplasms↗
PubMed1987

Cutaneous necrotizing granulomatous vasculitis with evolution to T cell lymphoma.

The evolution of unusual cutaneous vasculitis to a systemic T cell lymphoma was observed over a 12-year period. Precise classification of the skin biopsy specimens during the course of this patient's illness was difficult. Different observers suggested malignant hemangioendothelioma, malignant lymphoma, regressing atypical histiocytosis, and granulomatous vasculitis. In retrospect, the biopsy specimens likely represented the spectrum of cutaneous lymphomatoid granulomatosis. This condition is yet another example of a reactive lymphoid proliferation proceeding to a malignant lymphoma.

Diagnosis, Differential↗
PubMed1986

Chemotherapy in invasive thymomas: five case reports.

We treated 5 cases of invasive thymomas with single agent and combination chemotherapy. A carcinoid tumor of the thymus had a 13-month objective response to monthly courses of a combination of DTIC, adriamycin, cytoxan, and vincristine. A second case of carcinoid achieved stabilization of disease with a combination of adriamycin, cyclophosphamide, and DTIC for 9 months and subsequently 10 months, with fluorouracil and methotrexate. A case of thymoma had stabilization of disease for 14 months with oral cytoxan and prednisone.

Antineoplastic Combined Chemotherapy Protocols↗
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↗
PubMed1983

Therapeutic management of small cell lung cancer. Fewer toxic reactions with lower chemotherapeutic drug dosages.

A treatment protocol for small cell lung cancer used attenuated drug dosages in an attempt to reduce toxic reactions without compromising effectiveness. Treatment consisted of cyclophosphamide, 50 mg orally daily, methotrexate, 1.25 mg orally daily, procarbazine hydrochloride, 50 mg orally daily, and vincristine sulfate, 10 micrograms/kg intravenously weekly, and was continued until relapse or for two years. Patients with limited disease were given concurrent radiation (4,000 to 5,000 rad, using standard fractionation) to the primary lesion and draining nodes. Fifty patients were evaluable for toxic reactions and survival: 22 with limited and 28 with extensive disease. Fifty-four percent of the patients with extensive disease responded; one (4%) had a complete response. Median survival of the patients with extensive disease was 20 weeks. Ninety-five percent of the patients with limited disease responded; 57% had a complete response. Median survival of these patients was 55 weeks; one-year survival was 59%, and 18-month survival was 36%. Three patients have discontinued therapy without relapse for 48, 22, and seven months. One patient remains disease free after undergoing therapy for 84 weeks. There were no treatment-related deaths, and only 4% of patients experienced WBC count nadirs of less than 1,000/cu mm. Patients with limited disease had long-term survivals comparable with those of other more toxic protocols.

Adult↗
PubMed1983

Therapy of malignant APUD cell tumors. Effectiveness of DTIC.

Eleven patients with malignant APUD tumors, five islet cell carcinomas, five carcinoid tumors and one medullary carcinoma of the thyroid were treated with DTIC. Nine of 11 patients benefitted from treatment. A literature review revealed that other APUD tumors responded when treated with DTIC. DTIC is a useful agent for treatment of malignant APUDomas, and may be the drug of choice for islet cell carcinoma of the pancreas.

Adenoma, Islet Cell↗
PubMed1980

Treatment of breast cancer with oral four-drug chemotherapy.

Seventy patients with advanced metastatic breast cancer were treated with an oral drug regime of prednisone, cytomel, cytoxan, and methotrexate. One half of the cases (50%) had a response. There were complete remissions in 7%, partial remissions in 27%, and arrests in 16%. The median duration of remissions was 8+ months. There was no significant difference in response between patients with predominant visceral or bone disease nor between pre- and post-menopausal women. One third of non-hormonally responsive patients responded to this treatment. Side effects consisted predominantly of glucocorticoid changes, including cushinoid facies and weight gain. The program was relatively bone marrow sparing. This drug regime is very convenient and safe to give on an outpatient basis.

Administration, Oral↗