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Biomedical subjects

A Surbone

Publications and source records attributed to A Surbone.

44 records · Page 3Linked to original sources
PubMed1990

Phase I and pharmacokinetic study of arabinofuranosyl-5-azacytosine (fazarabine, NSC 281272).

A Phase I clinical trial of 1-beta-D-arabinofuranosyl-5-azacytosine (ara-AC or fazarabine) given as a 72-h continuous infusion on a 21-day cycle was conducted in 27 adult patients with refractory cancer. The major toxicity was reversible granulocytopenia and thrombocytopenia. Dose-limiting toxicity was observed at a dose rate of 1.96 mg/m2/h in which Grade IV leukopenia (WBC less than 1,000/mm3) occurred in 4 of 11 patients and Grade IV thrombocytopenia (platelets less than 25,000/mm3) occurred in 3 of 11 patients. Plasma steady-state levels ranged from 0.13 to 0.6 microM for doses of 1.25 to 5.94 mg/m2/h. Mean total body clearance was 647 ml/min/m2. Minor clinical responses were seen in one patient with testicular cancer, one patient with colon cancer, one patient with breast cancer, and one patient with acute nonlymphocytic leukemia. Another patient with adenocarcinoma of unknown primary had stable disease during 13 cycles of therapy. Based on the results of this study, the recommended dose for Phase II studies of 1-beta-D-arabinofuranosyl-5-azacytosine administered as a 72-h continuous infusion is 2.0 mg/m2/h (48 mg/m2/day).

Adult↗
PubMed1988

Residual abdominal masses in aggressive non-Hodgkin's lymphoma after combination chemotherapy: significance and management.

When patients with aggressive lymphoma present with intraabdominal disease, a stable residual mass is frequently detected radiographically at the time of the clinical complete remission. To discern the optimal management for this clinical problem, we reviewed 241 patients with aggressive lymphoma treated at the National Cancer Institute (NCI) from 1977 to 1986. Seventy-two/241 patients (30%) had an abdominal mass at diagnosis and 29/72 (40%) were left with a radiographically detectable residual mass at clinical complete remission. The likelihood of a residual mass was much higher for patients with bulky disease (P2 less than .0003) (two-tailed test [P2]). Twenty-nine patients had radiologically stable residual masses after therapy, and of 22 (76%) with pathologic evaluations, 21 had negative specimens (95%) and one was positive (5%). None of the patients with negative pathologic evaluation has relapsed in the abdominal site (median follow-up, 31 months). Seven patients were observed clinically without laparotomy: five are alive, without evidence of disease, at 2 to 9 years; two relapsed with disseminated disease within 2 months of chemotherapy. Initial tumor size and size of the residual mass did not correlate with residual disease, since residual masses identified by radiographic examination did not usually harbor viable lymphoma cells. Aspiration cytology was negative for residual tumor in 15/16 cases. One negative result was not confirmed at laparotomy, presumably due to sampling error. The one positive aspiration was followed by a negative laparotomy, possibly due to subsequent tumor necrosis. Restaging laparotomy has a low yield. In most patients with aggressive lymphoma who have otherwise completely responded to carefully administered full-dose combination chemotherapy, stable residual abdominal masses can be closely followed clinically without surgical exploration.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Treatment of the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex with a regimen of 3'-azido-2',3'-dideoxythymidine (azidothymidine or zidovudine) and acyclovir. A pilot study.

On the basis of observation that acyclovir potentiates the in-vitro antiviral activity of 3-azido-2',3'-dideoxythymidine (also known as azidothymidine or zidovudine) against human immunodeficiency virus (HIV), we administered a regimen of azidothymidine and acyclovir to eight patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. An oral regimen of 100 mg of azidothymidine and 800 mg of acyclovir every 4 hours was in general well tolerated, with the principal toxicity being megaloblastic erythroid changes. The pharmacokinetics of the two drugs were independent of each other. Six patients received the drug combination for at least 10 weeks; all had increased numbers of T4+ lymphocytes (P = 0.028), and two of three assessable patients had reversal of anergy. Two patients tested positive for serum HIV p24 antigen at entry, but became negative with treatment. Data for this small group suggest that this drug combination can be tolerated in patients with severe HIV infections; this study can be used as a basis for larger studies of this drug combination.

AIDS-Related Complex↗
PubMedDate not supplied

Spontaneous release of interferon as a predictor of clinical evolution in HIV-positive subjects.

In order to establish a correlation with disease progression we prospectively evaluated ten clinical and immunologic parameters in 102 consecutive HIV-positive subjects. The eight immunologic variables were: in vitro spontaneous interferon release by peripheral blood monocytic cells, alpha- and gamma-interferon production induced by Newcastle Disease Virus and PHA, Multitest Mérieux score, PHA- and CON-A-induced lymphocyte transformation, absolute number of CD4+ cells and CD4/CD8 ratio, respectively. The two baseline clinical variables were risk factor and disease presentation. Generalized Wilcoxon analysis indicated a significant correlation of one clinical (disease presentation at entry) and three immunologic variables (spontaneous interferon release, CD4+ cell number, Multitest Mérieux) with disease progression. Baseline spontaneous release of alpha, acid-labile interferon showed the best correlation with disease progression, and appeared to be significantly associated with CD4+ cell loss. Spontaneous release of acid-labile alpha interferon by mononuclear cells in vitro could be highly predictive of disease evolution in HIV-Ab positive, AIDS-free subjects.

Evaluation Studies as Topic↗
PubMedDate not supplied

An experimental analysis of classically conditioned nausea during cancer chemotherapy.

This study investigated classical conditioning in women undergoing outpatient adjuvant chemotherapy for breast cancer. Breast cancer chemotherapy outpatients were randomly assigned either to an Experimental Group (exposed to a distinctive stimulus before each infusion of chemotherapy) or to a Control Group. After repeated infusions of chemotherapy, patients' responses to the experimental stimulus were assessed in a location not associated with chemotherapy. Experimental Group patients had increased nausea (self-reported on a visual analog scale) following the presentation of the experimental stimulus at this test trial, whereas Control Group patients did not. Two other measures of nausea corroborated these results. Post hoc statistical analyses confirmed predictions based on conditioning theory. This conditioning model of anticipatory nausea bears witness to the relevance of classical conditioning in clinical medicine.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

[Autotransplantation in lymphomas: is it effective?].

Recent data suggest that intensive chemotherapy, with or without radiation, followed by a bone marrow autotransplant is effective in advanced intermediate and high-grade non-Hodgkin lymphoma (predominantly large-cell lymphoma). We analyzed 12 studies of the autotransplants to determine outcomes. The results were compared to data from 29 chemotherapy studies. Complete remissions were reported in 53 percent of autotransplant recipients versus 17 percent of persons receiving chemotherapy. Two-year disease-free survival was 16 percent and 3 percent, respectively. It is uncertain whether these differences reflect subject selection or time to treatment (time censoring) biases in the autotransplant cohort. A randomized trial is needed to determine if autotransplants are superior to chemotherapy. Also unknown is whether similar results might not be obtained with higher doses of chemotherapy without an autotransplant.

Antineoplastic Agents↗
PubMedDate not supplied

[Kinetics of breast neoplasms].

Breast cancer is a disease moderately responsive to chemotherapy. While its curability is inversely related to the tumor burden, a relevant number of patients still progress to metastatic disease even after adjuvant chemotherapy. Also, high-dose chemotherapy appears promising, but can not yet be considered ultimately curative of breast cancer. Different variables, biological, kinetic and treatment-related, account for the clinical behaviour of this disease. In order to improve its curability, they will all need to be taken into account in planning future treatment strategies. One of the most effective ways to understand and predict the clinical behaviour of breast cancer is the development of appropriate mathematical models explaining its growth-patterns. Aim of this paper is to review the two fundamental models, the exponential and the Gompertzian. The exponential model is at the basis of the Skipper-Schabel and the Goldie-Coldman hypotheses, while the Norton-Simon hypothesis has been formulated from the gompertzian model. The latter appears to better fit the vast amount of clinical data which are presently available: from Bloom's analysis of untreated breast cancer patients, to the results of large clinical trials, to the data emerged from the recent meta-analysis. Characteristic of a gompertzian growth pattern is that exponential growth is matched by exponential retardation of growth. In 1943 Delbruck and Luria demonstrated that random mutations could account for the development of virus resistance in bacteria and were able to estimate the rate of mutation as a function of the growth rate of bacteria. Shortly after Law demonstrated that resistance to methotrexate in murine leukemia occurred similarly. The concept of combination chemotherapy actually derived from the idea that cancer cells could be resistant to chemotherapy even before exposure to it. Goldie and Coldman applied the Delbruck/Luria model to hypothesize the use of non cross-resistant alternating combination chemotherapy as a better way to eliminate the risk of resistance. They also suggested that many different drugs were to be used as soon as possible, when the tumor size is still small. Most of their predictions were based on the Skipper/Schabel model of the exponential growth of cancer and on its deriving log-kill model. A large amount of clinical data are now suggesting that the behaviour of breast cancer is best described by gompertzian growth: in particular, gompertzian growth is a tenable model of breast cancer growth for both the unperturbed and the perturbed (by treatment) states.(ABSTRACT TRUNCATED AT 400 WORDS)

Breast Neoplasms↗