Biomedical subjects

J Wolter

Publications and source records attributed to J Wolter.

At least 19 recordsLinked to original sources

PubMed2005

Effects of lowering the aluminium content of a dTpa vaccine on its immunogenicity and reactogenicity when given as a booster to adolescents.

As aluminium in vaccines has been associated with the incidence of local side effects occurring after vaccination, this observer-blind randomised clinical trial was designed to evaluate the effect of lowering the aluminium content of a combined reduced-antigen-content dTpa vaccine on immunogenicity and safety when administered to healthy adolescents aged 10-18 years. A total of 647 subjects were enrolled, 224 (35%) received a dTpa formulation with 0.5 mg aluminium, 209 (32%) a formulation with 0.3 mg aluminium and 214 (33%) a formulation with 0.133 mg aluminium. One month after boostering, all subjects were seroprotected against diphtheria and tetanus toxoids. All subjects were seropositive for anti-FHA and anti-PRN but 4% of the initially seronegatives in both reduced aluminium groups did not seroconvert for anti-PT. Booster responses did not differ significantly between groups for any antibody, but post booster vaccination anti-PT GMC's differed significantly between groups and decreased when vaccine aluminium content decreased. No clear difference between study groups in local or general side effects was demonstrated. The most frequently reported symptoms after vaccination were injection site pain (89.5-90.7%), fatigue (42.1-47.4%) and headache (41.1-45.1%). This study showed that the aluminium content has a specific influence on the immunogenicity of this dTpa vaccine.

Adjuvants, Immunologic↗

PubMed2002

Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: a randomised trial.

BACKGROUND: Relentless chronic pulmonary inflammation is the major contributor to morbidity and mortality in patients with cystic fibrosis (CF). While immunomodulating therapies such as prednisolone and ibuprofen may be beneficial, their use is limited by side effects. Macrolides have immunomodulatory properties and long term use dramatically improves prognosis in diffuse panbronchiolitis, a condition with features in common with the lung disease of CF. METHODS: To determine if azithromycin (AZM) improves clinical parameters and reduces inflammation in patients with CF, a 3 month prospective randomised double blind, placebo controlled study of AZM (250 mg/day) was undertaken in adults with CF. Monthly assessment included lung function, weight, and quality of life (QOL). Blood and sputum collection assessed systemic inflammation and changes in bacterial flora. Respiratory exacerbations were treated according to the policy of the CF Unit. RESULTS: Sixty patients were recruited (29 men) of mean (SD) age 27.9 (6.5) years and initial forced expiratory volume in 1 second (FEV1) 56.6 (22.3)% predicted. FEV1% and forced vital capacity (FVC)% predicted were maintained in the AZM group while in the placebo group there was a mean (SE) decline of -3.62 (1.78)% (p=0.047) and -5.73 (1.66)% (p=0.001), respectively. Fewer courses of intravenous antibiotics were used in patients on AZM (0.37 v 1.13, p=0.016). Median C reactive protein (CRP) levels declined in the AZM group from 10 to 5.4 mg/ml but remained constant in the placebo group (p<0.001). QOL improved over time in patients on AZM and remained unchanged in those on placebo (p=0.035). CONCLUSION: AZM in adults with CF significantly improved QOL, reduced CRP levels and the number of respiratory exacerbations, and reduced the rate of decline in lung function. Long term AZM may have a significant impact on morbidity and mortality in patients with CF. Further studies are required to define frequency of dosing and duration of benefit.

Adolescent↗

PubMed2001

Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2.

BACKGROUND: The HER2 gene, which encodes the growth factor receptor HER2, is amplified and HER2 is overexpressed in 25 to 30 percent of breast cancers, increasing the aggressiveness of the tumor. METHODS: We evaluated the efficacy and safety of trastuzumab, a recombinant monoclonal antibody against HER2, in women with metastatic breast cancer that overexpressed HER2. We randomly assigned 234 patients to receive standard chemotherapy alone and 235 patients to receive standard chemotherapy plus trastuzumab. Patients who had not previously received adjuvant (postoperative) therapy with an anthracycline were treated with doxorubicin (or epirubicin in the case of 36 women) and cyclophosphamide alone (138 women) or with trastuzumab (143 women). Patients who had previously received adjuvant anthracycline were treated with paclitaxel alone (96 women) or paclitaxel with trastuzumab (92 women). RESULTS: The addition of trastuzumab to chemotherapy was associated with a longer time to disease progression (median, 7.4 vs. 4.6 months; P<0.001), a higher rate of objective response (50 percent vs. 32 percent, P<0.001), a longer duration of response (median, 9.1 vs. 6.1 months; P<0.001), a lower rate of death at 1 year (22 percent vs. 33 percent, P=0.008), longer survival (median survival, 25.1 vs. 20.3 months; P=0.01), and a 20 percent reduction in the risk of death. The most important adverse event was cardiac dysfunction of New York Heart Association class III or IV, which occurred in 27 percent of the group given an anthracycline, cyclophosphamide, and trastuzumab; 8 percent of the group given an anthracycline and cyclophosphamide alone; 13 percent of the group given paclitaxel and trastuzumab; and 1 percent of the group given paclitaxel alone. Although the cardiotoxicity was potentially severe and, in some cases, life-threatening, the symptoms generally improved with standard medical management. CONCLUSIONS: Trastuzumab increases the clinical benefit of first-line chemotherapy in metastatic breast cancer that overexpresses HER2.

Adult↗

PubMed2000

Costs or benefits of emotional conditioning on cognitive processing?

We report on two experiments using a transfer-of-control procedure in evaluating costs or benefits of emotionally relevant stimuli on the processing of a cognitive task. In differential conditioning the impact of Pavlovian conditioning usually is examined by contrasting instrumental responses in the presence of an excitatory conditioned stimulus (CS+) and an inhibitory conditioned stimulus (CS-). We expanded this comparison by introducing a neutral third condition. This additional neutral condition served as a within subject control for evaluating whether the CS+ increased responding and/or the CS- decreased responding. Both experiments yielded the same result; the CS- slowed down cognitive processing while the CS+ had no impact. Thus, the proposed transfer-of-control procedure may serve as a reliable and valid research tool in the evaluation of motivation and emotion in humans.

Adult↗

PubMed1999

[Testing of the effect of classic conditioning stimuli in human experiment by means of the transfer of control paradigm].

Pavlovian conditioning in animals is often evaluated by means of transfer of control experiments. With human subjects, however, only very few studies have been conducted and the outcomes were often not in accordance with theoretical explanations based on studies with animals. A theoretical framework is presented that tries to integrate the results of the human conditioning paradigm and the animal conditioning paradigm as well, with reference to the well-known Yerkes-Dodson law. The experimental study with human subjects (N = 24) confirmed the predictions out of this framework, when a procedure similar to animal research is applied.

Adult↗

PubMed1999

Some nematodes and acanthocephalans from exotic ornamental freshwater fishes imported into Germany.

Five species of adult nematodes, unidentifiable nematode larvae, and three species of acanthocephalans, were found in freshwater ornamental fishes newly imported into Germany from Brazil, Colombia, Indonesia, Malaysia, Nigeria, Peru, Sri Lanka and Thailand. The following species were identified: Adult Nematoda: Pseudocapillaria tomentosa, Capillariidae gen. sp., Dichelyne hartwichi sp. n., Procamallanus (Spirocamallanus) pintoi and Spinitectus allaeri; Acanthocephala: Pseudogorgorhynchus arii gen. et sp. n., Neoechinorhynchus sp. and Pallisentis sp. The nematode Dichelyne hartwichi sp. n. (male only) from the intestine of Chelonodon fluviatilis (Hamilton) from Thailand is characterised mainly by the presence of minute cuticular spines on the tail tip, length of spicules (510 microns) and arrangement of caudal papillae. The acanthocephalan Pseudogorgorhynchus arii sp. n. from the intestine of Ariopsis seemanni (Günther) from Colombia represents a new genus Pseudogorgorhynchus gen. n., differing from other genera of the Rhadinorhynchidae mainly in possessing a small proboscis armed with markedly few (18) hooks arranged in six spiral rows. Spinitectus macheirus Boomker et Puylaert, 1994 and Spinitectus moraveci Boomker et Puylaert, 1994 are considered junior synonyms of Spinitectus allaeri Campana-Rouget, 1961.

Acanthocephala↗

PubMed1997

A phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma. Arimidex Study Group.

BACKGROUND: Anastrozole is a new oral aromatase inhibitor with highly potent and selective activity for the aromatase enzyme. In a Phase III trial, the efficacy and tolerability of anastrozole, given in doses of 1 and 10 mg orally once daily, and megestrol acetate, given in doses of 40 mg orally 4 times daily, were compared in 386 postmenopausal women with advanced breast carcinoma who progressed after tamoxifen therapy. METHODS: The trial was randomized, double blind for anastrozole, open label for megestrol acetate, parallel group, and multicenter. Patients were randomly assigned to receive anastrozole, 1 mg (n = 128); anastrozole, 10 mg (n = 130); or megestrol acetate (n = 128). The primary efficacy measures were time to progression and tumor response; secondary measures were time to treatment failure, duration of response, quality of life, and time to death. RESULTS: With a median duration of follow-up of 6 months, there was no statistical evidence of a difference between either 1 or 10 mg doses of anastrozole and megestrol acetate for any efficacy endpoint. According to rigid response criteria, 10%, 6%, and 6% of patients in the anastrozole 1 mg, anastrozole 10 mg, and megestrol acetate groups, respectively, had an objective response (complete response or partial response) and 27%, 24%, and 30% of patients in the respective groups had stable disease for a duration of 24 weeks or longer. Quality-of-life assessments revealed that anastrozole in a 1-mg dose was associated with better physical scores and anastrozole in a 10-mg dose with better psychologic scores than megestrol acetate. Both anastrozole and megestrol acetate were generally well tolerated. Among anticipated adverse events, gastrointestinal disturbance was more common among patients in the anastrozole groups, whereas weight gain occurred more frequently among patients in the megestrol acetate groups. Weight increases of 5% or more and 10% or more were more common among megestrol acetate-treated patients; moreover, patients in this group continued to gain weight over time. CONCLUSIONS: Anastrozole, given in doses of 1 and 10 mg once daily, represents a well tolerated and effective therapeutic option for the treatment of postmenopausal women with advanced breast carcinoma who progress after tamoxifen treatment.

Adult↗

PubMed1997

Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22.

PURPOSE: The National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated a randomized trial (B-22) to determine if intensifying but maintaining the total dose of cyclophosphamide (Cytoxan, Bristol-Myers Squibb Oncology, Princeton, NJ) in a doxorubicin (Adriamycin, Pharmacia, Kalamazoo, MI)-cyclophosphamide combination (AC), or if intensifying and increasing the total dose of cyclophosphamide improves the outcome of women with primary breast cancer and positive axillary nodes. PATIENTS AND METHODS: Patients (N = 2,305) were randomized to receive either four courses of standard AC therapy (group 1); intensified therapy, in which the same total dose of cyclophosphamide was administered in two courses (group 2); or intensified and increased therapy, in which the total dose of cyclophosphamide was doubled (group 3). The dose and intensity of doxorubicin were similar in all groups. Disease-free survival (DFS) and overall survival were determined using life-table estimates. RESULTS: There was no significant difference in DFS (P = .30) or overall survival (P = .95) among the groups through 5 years. At 5 years, the DFS of women in group 1 was similar to that of women in group 2 (62% v 60%, respectively; P = .43) and to that of women in group 3 (62% v 64%, respectively; P = .59). The 5-year survival of women in group 1 was similar to that of women in group 2 (78% v 77%, respectively; P = .86) and to that of women in group 3 (78% v 77%, respectively; P = .82). Grade 4 toxicity increased in groups 2 and 3. Failure to note a difference in outcome among the groups was unrelated to either differences in amount and intensity of cyclophosphamide or to dose delays and intervals between courses of therapy. CONCLUSION: Intensifying or intensifying and increasing the total dose of cyclophosphamide failed to significantly improve either DFS or overall survival in any group. It was concluded that, outside of a clinical trial, dose-intensification of cyclophosphamide in an AC combination represents inappropriate therapy for women with primary breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Tandem peripheral blood progenitor cell transplants as initial therapy for metastatic breast cancer.

PURPOSE: To investigate the use of two sequential courses of high-dose chemotherapy and peripheral blood progenitor cell (PBPC) transplant as initial therapy for patients with untreated metastatic breast cancer. The goal of the study was to maximize treatment intensity through the use of two non-cross-resistant regimens, each equal in intensity to that used in single transplants. METHODS: PBPC were collected after a course of granulocyte colony-stimulating factor (G-CSF) only or of cyclophosphamide, etoposide, and G-CSF. The first transplant regimen consisted of thiotepa (600 mg/m2), cyclophosphamide (6000 mg/m2), and carboplatin (800 mg/m2). After recovery from the first transplant, responding patients received a second course of therapy consisting of busulfan (16 mg/kg) and etoposide (60 mg/kg). RESULTS: Forty-four patients were enrolled. Five patients did not proceed to transplantation due to tumor progression during PBPC mobilization. Five patients achieved complete response after the first transplant, and 14 were in complete remission at the end of the therapy. Six patients remain free of disease after a median followup of 22 months (range 12-27+ months). The 2-year event-free survival for complete responders is 25.4% (standard error 14.4%). Engraftment was prompt, with a median of 8 and 13 days, respectively, to reach a neutrophil count of 500/mm3 and a platelet count of 50,000/mm3. As a result of the gastrointestinal toxicity of the first course, the median interval between transplants was 68 days. The toxicities of the second transplant course were principally hepatic and muco-cutaneous. Hepatic veno-occlusive disease occurred in 12 patients and was a contributor to the death of three. CONCLUSIONS: Rapid hematologic recovery achieved with PBPC made possible the administration of two courses of high-dose chemotherapy without compromising the intensity of either transplant regimen. The adverse effects of the second course, however, were substantially higher than predicted. The outcome of patients achieving a complete response is promising. Overall, the antitumor benefit of this approach in patients with previously untreated metastatic disease was not superior to that achieved with single transplants in patients responding to standard-dose chemotherapy.

Adult↗

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↗