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Biomedical subjects

A Decensi

Publications and source records attributed to A Decensi.

69 records · Page 4Linked to original sources
PubMed1993

Retinoids and tamoxifen in breast cancer chemoprevention.

Chemoprevention is a new branch of oncology which aims to use chemical agents to reduce the incidence of malignant diseases in humans. On the basis of a growing mass of experimental data, it is now felt that the importance of early, precursor lesions of clinically symptomatic cancer should be recognized. Just as in cardiovascular disease, there is now major emphasis on the natural history of tumors and some authors believe that the actual disease process is carcinogenesis, rather than cancer. Indeed, as the chemoprevention of cardiovascular illness with pharmacological agents that either lower blood cholesterol or prevent platelet aggregation is widespread, the effectiveness of different chemical compounds in preventing cancer or, at least in delaying its onset, is presently under investigation. For breast cancer, various agents have been suggested as having chemopreventive effects: vitamins C and E, difluoromethylornithine, selenium, retinoids and antiestrogens. Among retinoids, 4-(N-hydroxyphenyl)retinamide, fenretinide, is at present the most promising molecule, due to its ability to concentrate in the mammary gland. Attention has recently been focussed on tamoxifen because of its effectiveness in reducing the incidence of contralateral tumors in breast cancer patients. Finally, the recent discovery of the steroid receptor superfamily is expected to stimulate further research into combination chemoprevention (the use of multiple agents to achieve synergistic effects while diminishing toxicity). As retinoids and tamoxifen both increase the synthesis or activity or transforming growth factor-beta, a cytokine which is a potent inhibitor of epithelial cell proliferation, tamoxifen and fenretinide are now proposed as the first model of combination chemoprevention in breast cancer.

Breast Neoplasms↗
PubMed1993

Carboplatin in advanced hormone refractory prostatic cancer patients.

25 patients with measurable or evaluable metastatic prostate cancer, progressive after hormonal treatment, were treated weekly with carboplatin 150 mg/m2 intravenously. The weekly schedule allowed higher dose intensity carboplatin administration with respect to the common monthly cycles. Toxicity was manageable even in elderly patients with extensive bone metastases and consisted primarily of myelosuppression. 4 out of 24 evaluable patients (17%) had a partial response and 12 (50%) had disease stabilisation. The median response duration was 7 months. Prostate-specific antigen and prostatic acid phosphatase serial values showed a correlation with disease response in only 47 and 50% of patients, respectively. These results suggest that carboplatin possesses a moderate but definite activity in prostate cancer patients.

Acid Phosphatase↗
PubMed1993

Goserelin acetate with or without flutamide in the treatment of patients with locally advanced or metastatic prostate cancer. The Italian Prostatic Cancer Project (PONCAP) Study Group.

From March 1987 to December 1990, 373 patients with stage C and D prostate cancer were randomized to receive either goserelin acetate alone or goserelin acetate plus flutamide. At a median follow-up time of 24 months, there was no significant difference in the response rate, progression-free and overall survival between the two treatment groups. In particular, median time to progression was 18 months in the goserelin arm and 24 months in the combined treatment arm (P = 0.09). However, median time to progression in stage D patients was 12 months in both treatment groups. Median time to death was 32 and 34 months, respectively. The combination regimen produced a more rapid normalisation of prostatic acid phosphatase levels and a prompt relief of bone pain. However, significantly more patients in the combination arm experienced treatment-related side-effects such as diarrhoea and increases in transaminase levels. The concurrent use of goserelin acetate and flutamide does not seem to significantly improve the results that can be achieved with goserelin acetate alone.

Acid Phosphatase↗
PubMed1993

Long-term endocrine effects of administration of either a non-steroidal antiandrogen or a luteinizing hormone-releasing hormone agonist in men with prostate cancer.

The claimed ability of non-steroidal antiandrogens to preserve libido and sexual potency is sought as a potential improvement in the palliative management of prostate cancer. A critical issue for the clinical use of these compounds is, however, the reported evidence in the rat of an excessive increase in testosterone concentrations as a consequence of the androgen negative feedback interruption. On the other hand, the recovery of testicular function after long-term inhibition by luteinizing hormone-releasing hormone (LHRH) analogs is also an important concern in view of the proposed use of these compounds for the treatment of several non-malignant conditions. We addressed these issues by studying the long-term endocrine effects induced by the administration of either the non-steroidal antiandrogen nilutamide or the depot preparation of D-Trp6-LHRH in men with prostate cancer. Treatment with the antiandrogen induced a marked increase in gonadotropin levels, LH concentrations rising from a mean (SEM) of 17.5 +/- 1.6 to a maximum of 56.6 +/- 6.9 kU/l (p < 0.001), while mean testosterone and 17 beta estradiol-concentrations rose only by about 50% and 70% over pretreatment values, testosterone levels reaching a plateau after 1 month of treatment. In the subjects treated with the LHRH agonist, 6 months after discontinuation of long-term administration the mean (+/- SEM) LH had risen to 36.9 +/- 6.8 IU/l while mean testosterone levels were still as low as 1.7 +/- 0.7 and rose only to a maximum of 4.2 +/- 1 nmol/l after high-dose human chorionic gonadotropin loadings.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Phase II study with lonidamine in the treatment of hormone-refractory prostatic cancer patients.

Twenty-one patients with metastatic prostate cancer who had become refractory to hormonal therapies received lonidamine (150 mg tid and 600 mg daily dose in 17 and 4 patients, respectively). In all but 4 patients, treatment was continued until disease progression or the development of severe toxicity. Toxicity was minimal and reversible (score 1 or 2) and included myalgia (8 cases), arthralgia (6 cases), gastrointestinal toxicity (11 cases), fatigue (14 cases) and testicular pain (9 cases). The response was evaluated after at least one month of therapy with lonidamine, according to NPCP-USA recommendations. Of 21 patients who entered the study, only 15 were evaluable for response; 2 died (1 for severe toxicity and 1 for drug-unrelated reasons). No objective response was obtained in the series. In fact, only 6 patients achieved stable disease and 9 progressed. Median survival time from the beginning of treatment was no longer than that of patients in a similar condition who were treated with standard palliative maneuvers. We conclude that this therapeutic approach with lonidamine is not active in hormone-refractory prostatic cancer patients with distant metastasis.

Aged↗
PubMed1992

Activity of 4-HPR in superficial bladder cancer using DNA flow cytometry as an intermediate endpoint.

The ability of the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) to affect the outcome of previously resected superficial bladder cancer was investigated in a pilot study using DNA content flow cytometry and conventional cytology as intermediate endpoints. Twelve patients were treated with oral 4-HPR (200 mg daily) and compared with 17 non-randomized, untreated controls. The median interval between transurethral resection and 4-HPR administration was 5.5 months (range 0-36). The median follow-up period was 12 months (range 3-31) in the 4-HPR group and 9 months (range 2-22) in the control group. The proportion of patients with DNA aneuploid stemlines in bladder-washed cells decreased from 7/12 (58%) to 5/11 (45%) in the 4-HPR group, but increased from 7/17 (41%) to 10/17 (59%) in the control group. In patients with stable diploid profiles, mean (+/- SE) S-phase and G2+M-phase fractions decreased in the course of retinoid treatment from basal levels of 15.2 +/- 4.1% to 7.5 +/- 3.3% and 10.3 +/- 2.2% to 5.2 +/- 0.4%, respectively. The same parameters in the control group changed from basal levels of 14.6 +/- 3.4% to 12.4 +/- 2.7% and 9.8 +/- 1.6% to 12.6 +/- 1.6%, respectively. Positive or suspicious cytologic examinations were present in 3/12 (25%) treated cases prior to 4-HPR administration and all subsequently reverted to normal. The same parameter in the control group increased from 4/17 (24%) to 6/17 (35%) during follow-up. Impaired adaptation to darkness was recorded in 4 patients, and transient dermatologic alterations were observed in one-third of the patients, requiring dose reduction in one case.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Phase II study of the pure non-steroidal antiandrogen nilutamide in prostatic cancer. Italian Prostatic Cancer Project (PONCAP).

The activity of the pure non-steroidal antiandrogen nilutamide as a single agent was evaluated in 44 patients with metastatic carcinoma of the prostate. Objective (partial) response rates (95% confidence limits) were 38.5 (18.7)% in 26 previously untreated patients and 5.5 (11%) in 18 patients progressing on primary androgen suppressive procedures. The most frequent side-effects were decreased adaptation to darkness (29.5%), slight nausea (31.8%) and alcohol intolerance (18.2%). In addition, treatment was discontinued in 3 patients because of gastrointestinal symptoms. A non-significant increase in testosterone levels was shown in the untreated group during the first month of treatment, after which the levels remained stable. About half of the sexually active men claimed the maintenance of libido and sexual potency during treatment. Although our study confirms a significant incidence of visual disturbances, the activity data coupled with the ability of maintaining sexual interest suggest that single therapy with non-steroidal antiandrogens may deserve comparison to conventional endocrine treatment in controlled trials.

Aged↗
PubMed1990

Zoladex with or without flutamide in the treatment of locally advanced or metastatic prostate cancer: interim analysis of an ongoing PONCAP study. Italian Prostatic Cancer Project (PONCAP).

Since March 1987, 304 evaluable patients with stage C and D prostate cancer have been entered into a prospective trial comparing Zoladex and Zoladex plus flutamide. To date, there has been no significant difference in over-all and progression-free survival between the 2 treatment groups. However, combined treatment produced a higher response rate (particularly in stage D patients) and a more rapid normalization of abnormal prostatic acid phosphatase levels. In addition, more prompt relief of bone pain was evident in the Zoladex plus flutamide group. However, significantly more side-effects were associated with combined treatment. These findings should be considered with caution because they form an interim analysis, and follow-up time is short. The results do suggest, however, that there is no particular advantage in using a combination of Zoladex plus flutamide compared to adding flutamide on failure of treatment with Zoladex alone.

Aged↗
PubMed1988

Estramustine phosphate (estracyt) following androgens in men with refractory stage D2 prostate cancer.

Twenty-two orchiectomized men with progressive stage D2 prostate cancer were treated with a 3-week cycle of estramustine phosphate (EMP: from day 3 to day 21) and androgen priming (from day 1 to day 4). A partial response according to the NPCP-USA criteria was shown in 4 of 20 evaluable patients. Median progression-free survival of all patients was 24 weeks (range, 4-48) and median survival, 42 weeks (range, 4-112). Although in two cases treatment had to be stopped due to a marked increase in bone pain, no life-threatening side effects were observed. The androgen sensitivity of tumors was supported by the occurrence of increase in prostatic phosphatase and in bone pain in most patients. In this group of patients, androgen priming did not seem to potentiate the effectiveness of EMP, our results being comparable to those previously reported using EMP alone.

Aged↗
PubMed1988

Long-acting (depot) D-TRP-6 LH-RH (Decapeptyl) in prostate cancer. An Italian multicentric trial.

Ninety-five patients with stage C (C1 + C2) or D (D1 + D2) prostatic carcinoma were treated with the long-acting formulation of D-TRP-6 LH-RH (Decapeptyl) for up to 39 months. Of 88 patients evaluable for response, about one-half showed an objective response. In most cases, subjective improvement with relief of bone pain and/or urinary symptoms was obtained. Five patients claimed a mild increase in bone pain and one patient a slight worsening of dysuria following the first injection. Median progression-free survival was 13.1 and 16.4 months in patients with stage D2 and D1, respectively. Median survival in stage D2 patients was 27.6 months. These results indicate that the depot formulation of D-TRP-6 LH-RH offers an effective therapeutic alternative for patients with advanced prostatic cancer.

Aged↗
PubMed1987

Long-term results with a long-acting formulation of D-TRP-6 LH-RH in patients with prostate cancer: an Italian prostatic cancer project (P.O.N.CA.P.) study.

Ninety-five patients with stage C (C1 + C2) or D (D1 + D2) prostatic carcinoma were treated with the depot formulation of D-TRP-6 LH-RH ("Decapeptyl") for up to 33 months. Serum testosterone (T) levels were significantly reduced to castration levels within 4 weeks and maintained persistently low. Similarly, LH levels were decreased, although they remained in the normal range. Stimulation tests with either Gn-RH or HCG in course of treatment showed the achievement of a complete pituitary desensitization and almost a complete down-regulation of testicular LH receptors. Of 88 patients evaluable for response, about one-half showed an objective response. In most cases, subjective improvement with relief of bone pain and/or urinary symptoms was obtained without major side effects. These results indicate that the depot formulation of D-TRP-6 LH-RH offers an effective therapeutic alternative for patients with advanced prostatic cancer.

Acid Phosphatase↗
PubMed1986

An overview of clinical trials with high-dose medroxyprogesterone acetate (HD-MPA) in endocrine-related tumors other than breast cancer.

High-dose medroxyprogesterone acetate (HD-MPA) has been successfully employed in the treatment of hormone-related tumors, especially advanced breast cancer. However, progestins in general and MPA in particular are considered a useful treatment also in other types of tumors such as endometrial, prostatic and renal cancer. Furthermore, MPA has been evaluated in tumors which are not classically considered hormone-related, such as ovarian cancer. Therapy with one of a number of progestational agents has been the conventional approach to the management of endometrial carcinoma not amenable to surgery or radiation therapy. Among the various synthetic progestins, MPA has been the most widely employed both by i.m. and oral routes, according to a variety of doses and schedules. Objective responses have been obtained in a percentage of women varying between 30 and 50% in the different series. While the role of MPA in the palliative treatment of advanced disease is well accepted, opinion is divided on the role of progestins in the adjuvant setting. On the basis of available data, it should be concluded that the usefulness of adjuvant therapy with progestins in high risk, early-stage endometrial cancer has not yet been clearly demonstrated. As far as prostatic cancer is concerned, data coming from comparative trials show that MPA is less effective than diethylstilbestrol (DES), and therefore should not be considered the first choice for previously untreated patients. However, it can achieve responses in patients who no longer respond or who are refractory to DES, and represents the treatment of choice for those patients who, due to their cardiovascular conditions, cannot be given estrogens.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMedDate not supplied

Chemoprevention trial of contralateral breast cancer with fenretinide. Rationale, design, methodology, organization, data management, statistics and accrual.

The Fenretinide (4-HPR) Breast Cancer Study is a randomized multicenter clinical trial originally designed and conducted by the investigators of the Istituto Nazionale Tumori of Milan. The study is sponsored by the National Cancer Institute of Bethesda and by the Italian National Research Council. The trial was designed to evaluate the effectiveness of the synthetic retinoid 4-HPR, at a dose of 200 mg per os every day for 5 years, in reducing the incidence of contralateral breast cancer in a population of patients previously operated on for breast cancer. Between 1987 and 1993, the Istituto Nazionale Tumori of Milan and 9 other collaborating Centers enrolled 2,972 women between the ages of 30 and 70 years who had been previously operated on for T1-T2 N- M0 breast cancer. This paper describes the rationale, design, methodology, organization, data management, statistics and accrual of the participating population.

Adult↗