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Biomedical subjects

J Wolter

Publications and source records attributed to J Wolter.

At least 19 recordsLinked to original sources
PubMed1994

Treatment of metastatic breast cancer with a split-course high-dose chemotherapy regimen and autologous bone marrow transplantation.

PURPOSE: We investigated the role of high-dose chemotherapy and autologous bone marrow transplantation (ABMT) as the initial systemic treatment in patients with hormone-unresponsive metastatic breast cancer. We studied a regimen involving a split-course schedule using sequential administration of two pairs of alkylating agents separated by 5 days of rest. The rest period was intended to provide time for recovery from the treatment-immediate adverse effects, thereby allowing further dose escalation. PATIENTS AND METHODS: The treatment consisted of thiotepa 225 to 300 mg/m2/d (days - 11 to -9), cisplatin 50 to 100 mg/m2/d (days - 11 and -3), and cyclophosphamide 60 mg/kg/d (days - 3 and -2). Dose escalation was performed in the initial 15 patients before reaching dose-limiting toxicities. When feasible, responding patients received posttransplant irradiation to sites of residual or prior bulky disease. Patients with bone marrow or CNS involvement, prior pelvic irradiation, or age greater than 55 years were excluded. RESULTS: Thirty-nine patients with measurable or assessable tumor were enrolled: 23 with visceral metastases, 11 with only soft tissue disease, and five with skeletal involvement. Twenty-five patients had received no chemotherapy for metastatic disease before transplantation. The dose-limiting toxicities of this therapy were renal and gastrointestinal. Six patients died from complications: four of a fungal infection and two of hemorrhage. A complete response was achieved in 14 patients (36%), three of whom are free of disease at 79+, 55+, and 40+ months after transplantation. Ten of 25 patients not treated with standard-dose chemotherapy for metastatic disease achieved a complete response (40%). The three patients in continuous remission were in the untreated relapse group. CONCLUSION: This single high-dose treatment achieved a relatively high complete response rate in patients with metastatic breast cancer and may have cured some of them. On the other hand, the split-course dose schedule as tested here did not permit significant dose-intensification.

Adult↗
PubMed1994

[Skin conduction as an indicator of cognitive and emotional processes].

Classical conditioning experiments can be used to study both cognition and emotions. In studies involving human subjects two different scores based on the human skin conductance response are generally used: the "first interval responses" (FIR) and the "second interval responses" (SIR). The SIR is thought to reflect cognitive but not emotional processes, while the FIR is assumed to reflect both. An experiment with two groups of subjects (n = 20 each) was run in order to demonstrate that the SIR indeed is able to reflect emotional processes. Each group was trained with five different conditioned stimuli, each of which was paired with a specific unconditioned stimulus. These unconditioned stimuli varied in aversiveness. Immediately after training, skin conductance responses to combinations of already trained conditioned stimuli were examined. The sequence of testing was varied across groups. Our results clearly showed that the SIR reflected aversiveness, while the FIR was confounded by orienting responses under these experimental conditions.

Adult↗
PubMed1993

[The action of atracurium and vecuronium in chronically hemodialyzed patients].

UNLABELLED: Reports on the duration of action of atracurium (Atr) and vecuronium (Vec) in patients with renal failure are contradictory. It is either stated that the duration is equal for both relaxants or that Atr acts for a longer duration. Because of these conflicting results, we measured the times for latency (tL), onset (tA), duration of action (tW), and recovery (tE) for both agents. METHODS: Fourty patients with end-stage renal failure on chronic haemodialysis were randomly assigned to receive either Atr (0.4 mg.kg-1 BW) or Vec (0.08 mg.kg-1 BW). After induction with thiopentone and 0.1 mg fentanyl, anaesthesia was maintained with nitrous oxide and 1 vol.% ethrane and expiratory CO2 partial pressure was kept between 4.6 and 4.9 kPa. If the twitch height of T1 regained 25% of the pre-relaxation value, 20% of the initial relaxant bolus was injected. Relaxation was monitored with a relaxograph after calibration of the device. After testing for a normal distribution, statistical analysis was done by Student's t-test. A value of P < or = 0.05 was chosen for statistical significance. RESULTS: There were no significant differences regarding tL (Atr: 1.0 +/- 0.5 min; Vec: 1.1 +/- 0.5 min) and tA (Atr: 5.5 +/- 2.1 min; Vec 4.1 +/- 2.4 min); tW (Atr: 21.3 +/- 13.1 min; Vec 31.7 +/- 15.6 min) and tE (Atr: 19.0 +/- 9.0 min; Vec 30.1 +/- 19.0) were significantly different. DISCUSSION: Our results are not in accordance with those authors who found in comparison with Atr an equal or shorter duration of action for Vec in patients with renal failure. If the duration of action is equal in subjects with no renal insufficiency, our measurements are in accordance with kinetic evaluations showing the same clearance and half-life for Atr in patients with and without renal insufficiency, but 40% diminished clearance and 60% prolonged half-life for Vec in renal insufficiency.

Adult↗
PubMed1991

Apparent beneficial effects of tamoxifen on bone mineral content in patients with breast cancer: preliminary study.

Eight postmenopausal women undergoing adjuvant treatment with tamoxifen (20 mg/day) for breast cancer had baseline pretreatment, and 6- and 12-month post-treatment dual-photon determinations of vertebral bone mineral content (BMC). BMC measured at 6 and 12 months increased over baseline in all subjects. These observations imply that women treated with tamoxifen may retain rather than surrender the protective effect of estrogen against osteoporosis.

Aged↗
PubMed1990

Adjuvant chemohormonal therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen compared with CMF for premenopausal breast cancer patients. An Eastern Cooperative Oncology Group trial.

The current trial was designed to assess whether the addition of prednisone or prednisone + tamoxifen would enhance the therapeutic effectiveness of 1 year of adjuvant CMF therapy. Premenopausal women with ipsilateral axillary node-positive breast carcinoma and known estrogen receptor (ER) status were randomized to receive 1 year of postoperative treatment with 12 28-day cycles of cyclophosphamide, methotrexate, 5-fluorouracil (CMF), CMF plus prednisone (CMFP), or CMFP plus tamoxifen (CMFPT). There were 553 analyzed cases with 188 receiving CMF, 183 CMFP, and 182 CMFPT. The overall time to relapse (TTR) and survival comparisons between the regimens are not statistically different at a median follow-up time of 7.7 years. The major subgroups currently with a suggestive TTR difference are greater than 3N+ (CMFPT greater than CMF, P = 0.07) and estrogen receptor-negative (ER-) greater than 3N+ (CMFPT greater than CMF, P = 0.03). Patients receiving CMFPT appeared to have a superior survival to CMF in the ER- greater than 3N+ cohort (P = 0.02). The following patient characteristics were associated with a significantly longer TTR: decreasing nodal involvement or tumor size, positive ER status, age greater than or equal to 40 years, and decreasing obesity. The favorable effects of decreasing nodal involvement, positive ER status, age 40 years or greater, and decreasing obesity carried over to survival. Development of amenorrhea was also significantly associated with improved survival (P = 0.001). Toxicity was increased by the addition of prednisone to CMF and by the addition of tamoxifen to CMFP. Overall relapse patterns were similar among the three regimens. The results of the current trial do not currently suggest an overall therapeutic benefit for adding prednisone or only 1 year of tamoxifen to CMF adjuvant treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Effects of tamoxifen treatment on plasma lipids and lipoprotein lipid composition.

Concern has been raised that long term treatment with the antiestrogen tamoxifen might predispose women to the rapid development of cardiovascular disease. Since estrogen-induced changes in plasma lipids confer protection to females from coronary heart disease, we have examined the impact of tamoxifen on lipoprotein levels and composition on eight posmenopausal women. After 3 months of tamoxifen treatment (10 mg, twice daily), no significant changes were observed in either whole plasma triglyceride (pre-Rx, 137 +/- 59; post-Rx, 157 +/- 110 mg/dL) or cholesterol (pre-Rx, 193 +/- 23; post-Rx, 204 +/- 14 mg/dL); plasma free (unesterified) cholesterol (FC), however, fell significantly (pre-Rx, 66.5 +/- 6.5; post-Rx, 59.6 +/- 4.6 mg/dL; P less than 0.05). Since plasma lecithin (L) was unchanged, the FC/L ratio declined significantly to levels observed in healthy menstruating women (pre-Rx, 95 +/- 0.16; post-Rx, 0.74 +/- 0.12 molar ratio; P less than 0.025). In low density lipoprotein (LDL), the concentrations of cholesterol and FC and the FC/L ratio all fell significantly (P less than 0.025, P less than 0.05, and P less than 0.025, respectively). Despite a tendency for high density lipoprotein2 cholesterol (HDL2-C) to increase (pre-Rx, 9.7 +/- 3.6; post-Rx, and 14.4 +/- 13.3 mg/dL; P less than 0.4) and phosphoinositol to fall, there were few clear-cut alterations in either HDL2 or HDL3 surface or core lipid composition. The combination of reduced HDL3 lysolecithin (P less than 0.025) associated with a posttreatment trend toward increased triglyceride/cholesterol esters ratios in both HDL subfractions are findings consistent with tamoxifen-induced inhibition of hepatic lipase. These changes in lipoprotein composition together with the fall in LDL cholesterol and increase in sex hormone-binding globulin (P less than 0.005) indicate that tamoxifen acts as an estrogen agonist on the liver. Since elevated LDL cholesterol levels and qualitatively altered lipoproteins enriched in FC are both associated with increased coronary risk, the improvement noted in these parameters after tamoxifen should allay to some degree anxiety about its use with regard to cardiovascular risk.

Cholesterol, HDL↗
PubMed1989

[Morphology of exudate membranes on intraocular lenses].

The morphological demonstration of exudative depositions on the surface of lens implants can be used as foundation for the understanding of the reactive processes that take place in human eyes in the years following cataract surgery with lens implantation. Clinical cases are used to demonstrate the practically unknown pathology of the different forms of reactive protein membranes together with the typical cellular reactions and the important differences in its fixation to the plastic surfaces. The reactive membrane on silicone lens implants is irregular. Deposition of fibrin, the reactive growth of fibroblasts on lens implants as an early stage of scarring, and the formation of hyaline bodies of different origin on lens implants are also demonstrated.

Adult↗
PubMed1988

Quantitative estrogen and progesterone receptor levels related to progression-free interval in advanced breast cancer patients treated with megestrol acetate or tamoxifen.

Estrogen receptor (ER) and progesterone receptor (PgR) levels have been reported to have prognostic significance with respect to disease-free survival in early-stage breast cancer patients. The current retrospective study was undertaken to determine whether ER and PgR levels, as well as other potential prognostic factors, might be related to a progression-free interval (PFI) during additive hormonal therapy in advanced-stage breast cancer patients. Eligibility requirements for this study included the following: histologically confirmed recurrent or metastatic breast cancer, known quantitative ER and PgR levels, postmenopausal status, treatment with either megestrol acetate or tamoxifen, and Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. The characteristics of the 105 patients included in these analyses were as follows: median age, 62 years; median disease-free interval (DFI), 523 days; median ER level, 44 fmol/mg; median PgR level, 52 fmol/mg; soft tissue-dominant disease, 37 patients (35%); bone-dominant disease, 36 patients (34%); visceral-dominant disease, 32 patients (31%); one site of disease, 60 patients (58%); two or more sites of disease, 45 patients (42%); treatment with megestrol acetate, 62 patients (59%); treatment with tamoxifen, 43 patients (41%). All of the independent variables listed immediately above were included in a multiple linear regression analysis in which PFI, expressed as log PFI, was the dependent variable. In this analysis, a positive linear relationship was observed between log PFI and the following independent variables: log ER, log PgR, and age (r2 = 0.329). An alternative model (r2 = 0.350) was derived, in which previous treatment with chemotherapy was negatively related to log PFI. However, it appears that previous treatment with chemotherapy could be a "proxy variable," because patients who had been treated with chemotherapy previously were significantly younger and had significantly lower ER (P = 0.0001) and PgR levels (P = 0.0004). None of the other independent variables were included in these models. If the assumption that PFI is a measure of the effectiveness of hormonal therapy is true, these results suggest that quantitative ER and PgR levels and age supersede other traditional predictor variables in predicting the hormonal responsiveness of individual breast carcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Megestrol acetate as primary hormonal therapy for advanced breast cancer.

The records of 133 patients treated with megestrol acetate as primary hormonal therapy for advanced breast cancer were reviewed retrospectively, using International Union Against Cancer (UICC) criteria for response. The median age was 65 years, 121 patients were over age 50, and the age range was 39 to 94 years. Response rates (complete response [CR] + partial response [PR]/total) by qualitative receptor level, with levels of 10 fmol/mg of protein considered positive, were as follows (ER = estrogen receptor, PgR = progesterone receptor): For ER + PgR+, 13 + 15/56 (50%); for those with one positive receptor, 0 + 12/47 (26%); for ER - PgR-, 0 + 0/12 (0%); and for receptor-unknown cases, 2 + 3/18 (14%). Response for ER less than 30 fmol/mg was 2 + 6/39 (21%); for ER 30 to 50, 1 + 5/16 (40%); and for ER greater than 50 fmol/mg, 11 + 15/56 (46%). For PgR less than 30, response was 0 + 6/37 (16%); for PgR 30 to 50 fmol/mg, 1 + 4/14 (36%); and for PgR greater than 50 fmol/mg, 12 + 13/54 (46%). For the 75 patients with a disease-free interval (DFI) of 2 years or less, the response rate was 5 + 1/75 (8%), and for the 58 patients with DFI greater than 2 years, 10 + 12/60 (37%). For patients with prior chemotherapy, 3 + 8/49 (22%) had an objective response. For those with no prior chemotherapy, 12 + 19/84 (37%) responded. Response by dominant site of disease was as follows: soft tissue 12 + 9/43 (49%), bone 2 + 13/49 (31%), viscera 2 + 5/41 (17%). Of these seven patients with visceral dominant disease who responded, all had PgR levels greater than 50 fmol/mg, all but one had an ER level over 100 fmol/mg, all but one were over age 65, and all but two received no prior chemotherapy. We conclude that megestrol acetate is effective initial hormonal therapy for patients with advanced breast cancer. It may have some role to play in the treatment of carefully selected cases with visceral disease.

Adult↗
PubMed1987

Phase II trial of aminothiadiazole in previously treated and untreated patients with advanced colorectal carcinoma: an Illinois Cancer Council Trial.

Eighty-three patients with advanced colorectal carcinoma were entered on a phase II trial of weekly iv aminothiadiazole (125 mg/m2) plus daily oral allopurinol (300 mg). There were five partial responses. Median survival of all patients on study was 36 weeks from entry (48 weeks for those without prior therapy and 34 weeks for those with previous chemotherapy). Toxicity was generally mild and consisted predominantly of stomatitis. In the dose given, aminothiadiazole has limited activity against metastatic colorectal cancer.

Clinical Trials as Topic↗
PubMed1986

Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project Trial.

In this National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial, 1,891 women with primary operable breast cancer and positive axillary nodes were randomized between Jan, 1977 and May 1980 to receive L-phenylalanine mustard (L-PAM) and 5-fluorouracil (5-FU) either with or without tamoxifen (TAM)-PFT. This report presents life table probabilities, cumulative odds ratios, and P values for disease-free survival (DFS) and survival at yearly intervals through 5 years of observation (mean time on study, 72 months). When patients were examined overall without regard for any discriminant associated with outcome, ie, age, number of positive nodes, or tumor receptor status, there was a significant prolongation of DFS (P = .002), but not survival through the fifth postoperative year. The benefit was almost entirely restricted to those greater than or equal to 50 years with greater than or equal to 4 positive nodes. In that group there was a 66% greater chance of remaining disease free if PFT was received (P less than .001), and there was also a significant survival benefit (P = .02). The advantage from PFT was found to be associated with tumor estrogen receptor (ER) and progesterone receptor (PR) as well as patient age and nodal status. Overall there was a significant improvement in DFS from PFT in those having tumors with an ER or PR level greater than or equal to 10 femtomole (fmol) (P = .01 and .009, respectively). No significant benefit in DFS or survival has been observed in patients less than or equal to 49 years old related either to nodes or tumor receptor status. Survival continues to be adversely affected by TAM in those patients (less than or equal to 49 years old), particularly when their tumors have a PR of 0 to 9 fmol (P = .007). In patients greater than or equal to 50 years old with four or more positive nodes, a significant DFS benefit persisted through the fifth year of observation in those having tumor ER or PR levels greater than 10 fmol (P less than .001 and .002). The advantage was observed in patients 50 to 59 years old as well as those 60 to 70. Women in the older decade demonstrated some advantage from PFT when their tumor ER or PR was 0 to 9 fmol. The most likely explanation for this finding is analytical error in receptor analyses.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1985

Megestrol acetate used as primary hormonal therapy in stage D prostatic cancer.

The majority of patients with advanced prostatic cancer respond either to castration or estrogen therapy. In an attempt to identify an alternative hormonal therapy, 25 symptomatic stage D prostate cancer patients were treated with megestrol acetate as initial hormonal therapy. Thirty-three patients were evaluable for response as defined by the National Prostatic Cancer Project criteria. Partial remission was observed in 11 patients and stable disease in 5, with an overall response rate of 70%. The projected median duration of response and survival were 10 and 20 months, respectively. Weight gain was common, but only two patients showed evidence of fluid retention. Gynecomastia, thromboembolic episodes, and gastrointestinal side effects were not observed in this group of patients, though two patients had increased pain shortly after therapy was initiated. Thus, in advanced prostatic cancer, megestrol acetate is effective primary therapy with minimal side effects.

Aged↗
PubMed1985

Primary hormonal therapy of advanced breast cancer with megestrol acetate: predictive value of estrogen receptor and progesterone receptor levels.

Estrogen (ER) and progesterone receptor (PR) levels in human breast cancer have been shown to have value in predicting response to a variety of hormonal therapies. However, the relationships between steroid receptor levels and tumor response and survival in patients treated with progestational agents for primary hormonal therapy have not been clearly defined. Forty-three advanced breast cancer patients, whose tumors had been assayed for ER and PR were treated with megestrol acetate as initial hormonal therapy. Twenty-five patients had ER and PR levels greater than 10 femtomole/mg cytosol protein, and the median ER and PR levels for the entire group were 114 fmol/mg and 100 fmol/mg, respectively. The overall response rate (complete and partial) was 46%, with a median duration of response of 66 weeks. Seventy percent of patients whose ER and PR were greater than 10 fmol/mg responded: Step-wise discriminant analysis showed that ER and PR were significantly related to response and that PR was the best predictor of response (P = .0034). Similarly, both ER and PR were significantly related to survival (P = .0001 for PR and P = .021 for ER). These data indicate that megestrol acetate is effective primary hormonal therapy in advanced breast cancer patients, and that ER and PR levels were significantly related to response and to survival duration. PR proved to be the best predictor of response in this group of patients.

Aged↗
PubMed1983

Relation of estrogen and/or progesterone receptor content of breast cancer to patient outcome following adjuvant chemotherapy.

In 1977 the National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated a prospectively randomized clinical trial to evaluate the relative merits of 1-phenylalanine mustard and 5-fluorouracil (PF) with and without tamoxifen (T) as adjuvant therapy for patients with primary breast cancer and positive axillary nodes. A previous presentation of findings noted that there was a strong relationship between the outcome of those receiving PFT and the estrogen receptor (ER) and progesterone receptor (PR) content of their tumors. This report relates the outcome of the PF-treated patients in that trial with these tumor receptors. It indicates that the results observed following nonhormonal therapy (PF) are also related to tumor receptors. Both the disease-free survival (DFS) and survival (S) of women following PF therapy were influenced by the ER and PR content of their tumors. Subsequent to adjustment for other prognostic variables, the predictive influence of tumor ER persisted. Both the DFS (p = 0.0003) and the S (p = 0.00003) were significantly higher in those with greater than or equal to 10 fmol tumor ER than in those with less than 10 fmol ER. The PR significantly added to the predictive value of ER. Thus, this analysis is the first to demonstrate that having information on both ER and PR is important for predicting outcome of patients receiving adjuvant chemotherapy. The study does not provide information which correlates receptor status with the response of patients to adjuvant chemotherapy since there is no similar nonchemotherapy-treated group of patients in the trial. The findings continue to emphasize that there is a heterogeneity in outcome of breast cancer patients to adjuvant chemotherapy which is related to an increasing number of host and tumor variables. For proper assessment of overall results, it is essential that analyses employ tests for interaction to indicate homogeneity or heterogeneity of patient subsets and that adjustments be made for imbalances in tumor ER and PR as well as in other prognostic factors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1982

Vindesine: phase II evaluation in colon cancer and description of its platelet stimulating activity.

Fifteen previously treated patients with measurable metastatic colon carcinoma were entered into a phase II study of vindesine, 3 mg/m2/week IV. Fourteen patients were evaluable for response. No objective tumor response was observed; however, seven patients experienced stable disease lasting 9, 10, 13, 15, 16, 19, and 26 weeks. Neurologic toxicity was the most common nonhematologic side-effect noted, manifesting as abdominal pain, constipation, paralytic ileus, or paresthesias. Leukopenia was observed in 16% of the 104 weekly courses. Nine patients had a 50% increase of their platelet counts above their pretreatment platelet counts; six patients had a doubling of their pretreatment platelet counts. Mean platelet counts revealed a linear increase with successive treatments during the initial 8 weeks of therapy. Serial CEA determinations demonstrated a parallel relationship with clinical progression in six of seven patients.

Adult↗