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N Rotmensz

Publications and source records attributed to N Rotmensz.

At least 19 recordsLinked to original sources
PubMed2002

Tamoxifen for breast cancer among hysterectomised women.

Tamoxifen is a candidate drug for prevention of breast cancer, although findings from trials have not been consistent. In our extended follow-up (median 81.2 months, IQR 66.0-87.2) of the Italian Tamoxifen Trial, this drug did not significantly protect against breast cancer in women at usual or slightly reduced risk of the disease (p=0.215). Use of hormone replacement therapy increased risk of breast cancer, and users of such treatment who were randomly allocated to tamoxifen had a rate of breast cancer that was close to that of never-users. So far, no woman has died from breast cancer in this study. Decisions about introduction of tamoxifen to reduce risk of breast cancer remain important and open questions.

Anticarcinogenic Agents↗
PubMed2002

Very young women (<35 years) with operable breast cancer: features of disease at presentation.

BACKGROUND: Breast cancer rarely occurs in young women. Our knowledge about disease presentation, prognosis and treatment effects are largely dependent upon older series. MATERIALS AND METHODS: We evaluated biological features and stage at presentation for 1427 consecutive premenopausal patients aged < or = 50 years with first diagnosis of invasive breast cancer referred to surgery at the European Institute of Oncology from April 1997 to August 2000. A total of 185 patients (13%) were aged < 35 years ('very young') and 1242 (87%) were aged 35-50 years ('less young'). The expression of estrogen receptors (ER), progesterone receptors (PgR), presence of vascular invasion (VI), grading (G), expression of Ki-67, HER2/neu overexpression, pathological stage according to TNM staging system (pTNM), pathological tumor size and number of axillary lymph node involvement were evaluated. RESULTS: Compared with less young patients, the very young patient group had a higher percentage of tumors classified as ER negative (P < 0.001), PgR negative (P = 0.001), higher expression of Ki-67 > or = 20% of cells stained; 62.2% versus 53%, (P < 0.001), vascular or lymphatic invasion (48.6% versus 37.3%, P = 0.006), and pathological grade 3 (P < 0.0001). There was no difference between the two groups for pT, pathological tumor size (pN) and number of positive lymph nodes. CONCLUSIONS: We conclude that compared with less young premenopausal patients, very young women have a greater chance of having an endocrine-unresponsive tumor, and are more likely to present with a higher grade, more extensively proliferating and vessel invading disease. Pathological tumor size, nodal status and number of positive axillary lymph-nodes have a similar distribution among the younger and the older cohorts, thus not supporting previous data indicating more advanced disease in younger patients at diagnosis of operable disease.

Adult↗
PubMed2002

How to decrease the non-compliance in a clinical trial.

BACKGROUND: A high compliance is an important scientific objective for a multicenter clinical trial and also an ethical responsibility. Some of non-compliance causes can be prevented during the enrollment phase by an accurate selection of subjects (quality of recruitment), other can be controlled after the recruitment, by a good organization of follow-up tests and visits (quality of organization). METHODS: The policy adopted in the Operative Center of the Delegazione Alto Lario della Lega Italiana per la Lotta contro i Tumori di Gravedona (Como) for obtaining a high compliance of women recruited in the Italian Tamoxifen Prevention Study are illustrated. RESULTS: The non-compliance rate of this center is low: 5.6 vs 23.3% of the whole Italian trial. CONCLUSIONS: The low non-compliance demonstrates the efficacy of the policy adopted.

Adult↗
PubMed2001

A randomized, prospective trial of central venous ports connected to standard open-ended or Groshong catheters in adult oncology patients.

BACKGROUND: Implanted central venous access is practiced extensively in oncology; however, information on the relevance of using the device with a valved catheter (Groshong), compared with an open-ended catheter, is scarce. The authors investigated the two types of catheters in a randomized trial using the same type of subcutaneous port and evaluated efficacy as well as early and late complications. METHODS: Three hundred four patients with malignant disease (solid tumors) who were eligible to receive intravenous chemotherapy were accrued during a 15-month period. After providing informed consent, the patients were assigned randomly to implantation of a titanium and silicone, rubber port (Dome Port; Bard Inc., Salt Lake City, UT) attached either to an 8.0-F silastic Groshongtrade mark catheter tube (experimental group) or to a 9.6-F silastic open-ended catheter tube (control group). Both catheters were manufactured by Bard Inc. Implantation, care, and follow-up followed the same protocol guidelines until removal of the device, death, or ending of the study. Power and color Doppler ultrasound examinations of internal jugular and subclavian veins were performed at 1 month and at 4 months or at anytime when a venous thrombosis was suspected. RESULTS: Three hundred two patients (99.3%) were evaluable, 150 patients in the control group and 152 in the experimental group. The median follow-up was 237 days. There was a trend toward more early complications in the experimental group (5.9%; 95% confidence interval [95% CI], 2.7-10.9%) than in the control group (2.7%; 95% CI, 0.7-6.7%), although the difference was not statistically significant (P = 0.26). There was also a trend toward more late complications in the experimental group (17.1%; 95% CI, 11.5-24.1%) compared with the control group (10.7%; 95% CI, 6.2-16.7%; P = 0.13), although the difference, again, was not statistically significant. The most frequent late complication was the inability to draw blood samples (12.5% in the experimental group and 2% in the control group; P < 0.001). Sepsis was observed in 1 patient and in 3 patients and venous thrombosis was observed in 6 patients and in 11 patients in the experimental and control treatment groups, respectively (P value not significant). CONCLUSIONS: In the tested clinical setting, the use of a Groshong catheter was not superior to a traditional, open-ended device in terms of early and late complications of the implant and its use. The theoretical justification for its superiority for more efficient use of the implantable device could not be substantiated.

Adult↗
PubMed2001

Phase II study of mitomycin-C and cisplatin in disseminated, squamous cell carcinoma of the uterine cervix. A European Organization for Research and Treatment of Cancer (EORTC) Gynecological Cancer Group study.

The aim of this study was to investigate the tumour response rate and toxicity of a combination chemotherapy consisting of mitomycin-C and cisplatin in patients with disseminated squamous-cell carcinoma of the uterine cervix. Chemotherapy consisted of mitomycin, 6 mg/m(2) intravenously (i.v.), and cisplatin, 50 mg/m(2) given i.v., both administered on day 1 of each cycle. The regimen was repeated at 4-weekly intervals. Mitomycin-C/cisplatin were used to treat 33 evaluable patients aged 29-67 years (median: 50 years). All patients except 1 had previously been treated with either surgery, radiation or both. At the initiation of chemotherapy, 8 patients had loco-regional and disseminated disease and 25 women had only distant metastases. The overall response rate was 42% (95% confidence interval (CI): 26-61%). Five complete and nine partial responses were observed with a median duration of response of 7.9 months (95% CI: 3.7-23.5 months). 9 patients had stable disease and 10 developed progressive disease during mitomycin-C/cisplatin-treatment. World Health Organization (WHO) grade III/IV side-effects were documented in 15 women, of whom 10 had gastro-intestinal toxicity, 3 had haematological toxicity, 1 had alopecia and 1 developed an allergic reaction to cisplatin. There were neither drug-related deaths nor severe or irreversible renal or hepatic dysfunction or peripheral neuropathy. The median progression-free survival was 5.0 months (95% CI: 3.6-6.2 months) for all patients and 10.5 months (95% CI: 6.2-15.2 months) for the responders. The median overall survival was 11.2 months (95% CI: 6.5-18.4 months).The mitomycin-C/cisplatin combination showed antitumour activity in the treatment of advanced or recurrent squamous-cell carcinoma of the uterine cervix. The regimen was well tolerated and could be administered on an outpatient basis.

Adult↗
PubMed2001

The Italian breast cancer prevention trial with tamoxifen: findings and new perspectives.

The Italian Tamoxifen Prevention Study includes 5408 healthy hysterectomized women aged 35-70 years who have been randomized to 20 mg/day of tamoxifen or placebo for 5 years. After 46 months median follow-up, an increased risk of venous vascular events (38 women on tamoxifen vs. 18 women on placebo, P = 0.0053), mainly consisting of superficial phlebitis, has been observed and 41 breast cancers have occurred (19 on tamoxifen vs. 22 on placebo, P = 0.64). However, subgroup analyses indicated a borderline significant reduction of breast cancer among women continuously on estrogen replacement therapy (ERT, mostly transdermal) and receiving tamoxifen, with 8 cases of breast cancer among 390 ERT users on placebo versus 1 case among 362 ERT users on tamoxifen (RR = 0.13, 95% CI = 0.02-1.02). Withdrawal rate (mainly due to menopausal symptoms) differed according to ERT use, with compliance being 78% and 75% at 3 and 5 years, respectively, for women who never took ERT, and 92% and 88% at 3 and 5 years, respectively, for women not on ERT at baseline, but who took ERT at some time during the trial. Pharmacokinetic and pharmacodynamic (surrogate end point biomarkers) studies showed that a lower dose of tamoxifen (such as 5 mg/day) does not affect the drug's activity on several biomarkers of both cardiovascular and breast cancer risk. We are therefore planning a multicenter placebo-controlled phase III trial in postmenopausal healthy women on hormone replacement therapy (HRT) to test whether the combination of HRT and low-dose tamoxifen retains the benefits while reducing the risks of either agent maintaining a high compliance rate.

Adult↗
PubMed2000

Sunscreen use and intentional exposure to ultraviolet A and B radiation: a double blind randomized trial using personal dosimeters.

A previous randomized trial found that sunscreen use could extend intentional sun exposure, thereby possibly increasing the risk of cutaneous melanoma. In a similarly designed trial, we examined the effect of the use of sunscreens having different sun protection factor (SPF) on actual exposure to ultraviolet B (UVB) and ultraviolet A (UVA) radiation. In June 1998, 58 European participants 18-24 years old were randomized to receive a SPF 10 or 30 sunscreens and were asked to complete daily records of their sun exposure during their summer holidays of whom 44 utilized a personal UVA and UVB dosimeter in a standard way during their sunbathing sessions. The median daily sunbathing duration was 2.4 hours in the SPF 10 group and 3.0 hours in the SPF 30 group (P = 0.054). The increase in daily sunbathing duration was paralleled by an increase in daily UVB exposure, but not by changes in UVA or UVB accumulated over all sunbathing sessions, or in daily UVA exposure. Of all participants, those who used the SPF 30 sunscreen and had no sunburn spent the highest number of hours in sunbathing activities. Differences between the two SPF groups in total number of sunbathing hours, daily sunbathing duration, and daily UVB exposure were largest among participants without sunburn during holidays. Among those with sunburn, the differences between the two groups tended to reduce. In conclusion, sunscreens used during sunbathing tended to increase the duration of exposures to doses of ultraviolet radiation below the sunburn threshold.

Adolescent↗
PubMed1998

Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study.

BACKGROUND: Tamoxifen is a candidate chemopreventive agent in breast cancer, although the drug may be associated with the development of endometrial cancer. Therefore we did a trial in hysterectomised women of tamoxifen as a chemopreventive. METHODS: In October, 1992, we started a double-blind placebo-controlled, randomised trial of tamoxifen in women (mainly in Italy) who did not have breast cancer and who had had a hysterectomy. Women were randomised to receive tamoxifen 20 mg per day or placebo, both orally for 5 years. The original plan was to follow the intervention phase by 5 years' follow-up. In June, 1997, the trialists and the data-monitoring committee decided to end recruitment primarily because of the number of women dropping out of the study. Recruitment ended on July 11, 1997, and the study will continue as planned. The primary endpoints are the occurrence of and deaths from breast cancer. This preliminary interim analysis is based on intention-to-treat. FINDINGS: 5408 women were randomised; participating women have a median follow-up of 46 months for major endpoints. 41 cases of breast cancer occurred so far; there have been no deaths from breast cancer. There is no difference in breast-cancer frequency between the placebo (22 cases) and tamoxifen (19) arms. There is a statistically significant reduction of breast cancer among women receiving tamoxifen who also used hormone-replacement therapy during the trial: among 390 women on such therapy and allocated to placebo, we found eight cases of breast cancer compared with one case among 362 women allocated to tamoxifen. Compared with the placebo group, there was a significantly increased risk of vascular events and hypertriglyceridaemia among women on tamoxifen. INTERPRETATION: Although this preliminary analysis has low power, in this cohort of women at low-to-normal risk of breast cancer, the postulated protective effects of tamoxifen are not yet apparent. Women using hormone-replacement therapy appear to have benefited from use of tamoxifen. There were no deaths from breast cancer recorded in women in the study. It is essential to continue follow-up to quantify the long-term risks and benefits of tamoxifen therapy.

Adult↗
PubMed1998

Doxorubicin vs epirubicin, report of a second-line randomized phase II/III study in advanced breast cancer. EORTC Breast Cancer Cooperative Group.

The EORTC Breast Cancer Cooperative Group carried out a randomized trial to compare doxorubicin with epirubicin as second-line chemotherapy in patients with metastatic breast cancer. Two hundred and fifty-nine patients with at least one site of metastatic disease entered this trial, of whom 232 patients were eligible. Treatment consisted of doxorubicin 75 mg m(-2) or epirubicin 90 mg m(-2) i.v. every 3 weeks. The overall response rates for doxorubicin and epirubicin were 36% and 28% respectively (P = 0.173). The median time to progression was 23 weeks for doxorubicin and 19 weeks for epirubicin (P = 0.063) and the median duration of response was 40 weeks for doxorubicin and 32 weeks for epirubicin (P = 0.059). The median survival was 47 weeks for doxorubicin and 44 weeks for epirubicin (P = 0.196). Leucocyte count on retreatment day (P = 0.011) and platelet nadir (P = 0.031) were significantly lower in the doxorubicin-treated group. Also mucositis (P < 0.001), diarrhoea (P = 0.005) and haemorrhage (P = 0.048) were significantly worse in the doxorubicin arm. Nine patients on doxorubicin and two patients on epirubicin experienced congestive heart failure (CHF). At the dose levels used in this study, no statistical differences in response rate and survival were found between the two treatment arms. Treatment with doxorubicin tended to result in a slightly longer duration of response and time to progression but doxorubicin was more toxic than epirubicin.

Adult↗
PubMed1998

Effect of tamoxifen and transdermal hormone replacement therapy on cardiovascular risk factors in a prevention trial. Italian Chemoprevention Group.

The combination of tamoxifen and transdermal hormone replacement therapy (HRT) may potentially reduce risks and side-effects of either agent, but an adverse interaction could attenuate their beneficial effects. We assessed the effects of their combination on cardiovascular risk factors within a prevention trial of tamoxifen. Baseline and 12-month measurements of total, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, platelets and white blood cells were obtained in the following four groups: tamoxifen (n = 1117), placebo (n = 1112), tamoxifen and HRT (n = 68), placebo and HRT (n = 87). The analysis was further extended to women who were on HRT at randomization but discontinued it during the 12-month intervention period (n = 33 on tamoxifen and n = 35 on placebo) and to women who were not on HRT but started it during intervention (n = 36 in both arms of the study). Compared with small changes in the placebo group, tamoxifen was associated with changes in total, LDL- and HDL-cholesterol of approximately -9%, -19% and +0.2% in continuous HRT users compared with -9%, -14% and -0.8% in never HRT users. Similarly, there was no interaction on platelet count. In contrast, the decrease in total and LDL-cholesterol levels induced by tamoxifen was blunted by two-thirds in women who started HRT while on tamoxifen (P = 0.051 for the interaction term). We conclude that the beneficial effects of tamoxifen on cardiovascular risk factors are unchanged in current HRT users, whereas they may be attenuated in women who start transdermal HRT while on tamoxifen. Whereas a trial of tamoxifen in women already on transdermal HRT is warranted, prescription of HRT during tamoxifen may attenuate its activity.

Breast Neoplasms↗
PubMed1995

[Italian study on the chemoprevention of breast cancer with tamoxifen].

There is currently a large breast cancer chemoprevention trial in Italy. The trial is based on the use of the antioestrogen tamoxifen, which is one of the most successful and most studied anticancer drugs. There is a strong evidence that this drug can prevent the growing of controlateral cancer in women previously operated for breast cancer. The chemoprevention trial using tamoxifen includes healthy women, aged 35 to 70 and hysterectomised. The participants are taking either 20 mg/day of tamoxifen or placebo for 5 years, in double blind; then they are followed-up clinically and instrumentally every 6 months for the further 5 years. The main end-point of the study is to verify the reduction of incidence and mortality from breast cancer. It was decided to recruit only hysterectomised women on the consideration that, according to some studies, tamoxifen could give an additional risk of endometrial cancer: the Italian study was especially designed with the intention of avoiding this unjustified risk.

Adult↗
PubMed1994

Phase II study of high-dose megestrol acetate in patients with advanced ovarian carcinoma.

The EORTC Gynaecological Cancer Cooperative Group conducted a phase II study of high dose oral megestrol acetate: 800 mg/day for 1 month followed by 400 mg/day as maintenance treatment, in heavily pretreated patients with ovarian cancer. Of 72 patients included in this study, 54 were fully evaluable for response and toxicity. The response rate was low with only 1 patient having a partial response, 9 patients with stable disease and 44 patients with progressive disease. The toxicity profile was low. However, 1 patient died after 2 months of treatment, and in 3 patients thrombo-embolic events occurred. Weight gain varied in 20 of the 61 patients from 0.5 to 16 kg. This study does not suggest that the overall 10% benefit from hormonal therapy for chemotherapy refractory ovarian cancer will improve by increasing the dose.

Adult↗
PubMed1991

"Classical" CMF versus a 3-weekly intravenous CMF schedule in postmenopausal patients with advanced breast cancer. An EORTC Breast Cancer Co-operative Group Phase III Trial (10808).

The "classical" CMF (cyclophosphamide/methotrexate/5-fluorouracil) schedule was compared with a modified 3-weekly intravenous CMF schedule in postmenopausal patients with advanced breast cancer, as concern had arisen as to whether the classical schedule was the optimal way to give these drugs. The response rate with classical CMF was 48% compared with 29% for intravenous CMF (P = 0.003). Response duration was similar at 11 months, but survival longer for the classical schedule (17 versus 12 months, P = 0.016). We conclude that classical CMF is the superior regimen and attribute this to the higher dose intensity achieved.

Aged↗
PubMed1991

Long-term tolerability of fenretinide (4-HPR) in breast cancer patients.

A group of 53 patients initially participating in a phase I trial with the synthetic retinoid fenretinide was assessed for the long-term tolerability of this compound. The patients were evaluated after 42 months of drug intake at a dose of 200 mg/day, including a 3-day drug interruption at the end of each month, by the following examinations: a dermatological visit; an ophthalmological evaluation including an ophthalmological questionnaire and an electroretinogram (ERG); a study on blood chemistry and plasma retinol levels; a study on bone densities and on skeletal X-rays; and finally a psychological evaluation including various tests for anxiety, depression and overall mood. The results show that prolonged administration of fenretinide is well tolerated. No acute nor severe toxicity was observed and thus this compound can be considered a good candidate for chemoprevention trials in a variety of patient populations.

Affective Symptoms↗