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E Simoncini

Publications and source records attributed to E Simoncini.

At least 19 recordsLinked to original sources
PubMed1998

The importance of the histologic grade of invasive breast carcinoma and response to chemotherapy.

BACKGROUND: Histologic grade is well recognized for its prognostic significance in cases of primary operable invasive breast carcinoma; however, the majority of studies in which grade has been assessed have been based on single-center trials. In addition, the role of grade in predicting response to chemotherapy has not been examined in many previous studies. METHODS: The authors assessed the value of Nottingham histologic grade (NHG) in a group of 465 patients enrolled in a multicenter, randomized International Breast Cancer Study Group clinical trial of adjuvant chemotherapy for patients with lymph node (LN) positive and LN negative primary breast carcinoma (formerly named Ludwig Trial V). RESULTS: NHG was a predictor of overall survival for both LN negative and LN positive patients (P=0.045 and P < 0.001, respectively). NHG was associated with a poorer prognosis for both LN positive and LN negative patients, with hazard ratios of 1.651 (P < 0.001) and 1.437 (P=0.045), respectively, for an increase of one grade. Among LN negative patients, this survival disadvantage was observed only for those who received perioperative chemotherapy. For LN positive patients, an increase of one grade resulted in a significant overall survival disadvantage regardless of whether prolonged or perioperative chemotherapy was given. For LN negative patients grouped by grade, there was no observed difference in overall or disease free survival according to whether perioperative chemotherapy or no adjuvant therapy was given. However, LN positive patients with Grade 3 tumors had a significantly greater overall and disease free survival benefit from prolonged chemotherapy than from perioperative chemotherapy (P=0.016 and P=0.013, respectively); LN positive patients with Grade 1 or 2 disease in both treatment arms had comparable overall and disease free survival. A strong correlation between the previously utilized Bloom-Richardson grading system (BRG) and NHG was observed (P < 0.001 and kappa=82%) and no apparent differences in overall and disease free survival were observed between the two systems. NHG did, however, identify a greater proportion of tumors as Grade 1, and BRG identified a greater proportion of breast carcinomas as Grade 3. CONCLUSIONS: This multicenter clinical study confirms the value of histologic grade, and the authors propose that this technique be used to identify Grade 3, LN positive patients who will benefit from prolonged rather than perioperative chemotherapy.

Antimetabolites, Antineoplastic↗
PubMed1998

Prognostic impact of amenorrhoea after adjuvant chemotherapy in premenopausal breast cancer patients with axillary node involvement: results of the International Breast Cancer Study Group (IBCSG) Trial VI.

Adjuvant chemotherapy-induced amenorrhoea has been shown to be associated with reduced relapses and improved survival for premenopausal breast cancer patients. Amenorrhoea was, therefore, studied to define features of chemotherapy (i.e. duration and timing) and disease-related factors which are associated with its treatment effects. We reviewed data from IBCSG Trial VI, in which accrual was between July 1986 and April 1993. 1196 of the 1475 eligible patients (81%) were evaluable for this analysis. The median follow-up was 60 months. Women who experienced amenorrhoea had a significantly better disease-free survival (DFS) than those who did not (P = 0.0004), although the magnitude of the effect was reduced when adjusted for other prognostic factors (P = 0.09). The largest treatment effect associated with amenorrhoea was seen in patients assigned to receive only three initial CMF courses (5-yr DFS: 67% versus 49%, no amenorrhoea; hazard ratio, 0.55; 95% confidence interval, 0.38 to 0.81; P = 0.002). DFS differences between amenorrhoea categories were larger for patients with ER/PR positive tumours (hazard ratio, 0.65; 95% confidence interval, 0.53 to 0.80; P = 0.0001). Furthermore, patients whose menses returned after brief amenorrhoea had a DFS similar to those whose menses ceased and did not recover (hazard ratio, 1.10; 95% confidence interval, 0.75 to 1.62; P = 0.63). The effects associated with a permanent or temporary chemotherapy-induced amenorrhoea are especially significant for node-positive breast cancer patients who receive a suboptimal duration of CMF chemotherapy. Cessation of menses, even for a limited time period after diagnosis of breast cancer, might be beneficial and should be prospectively investigated, especially in patients with oestrogen receptor-positive primaries.

Adult↗
PubMed1997

Menstrual cycle and timing of breast surgery in premenopausal node-positive breast cancer: results of the International Breast Cancer Study Group (IBCSG) Trial VI.

PURPOSE: It has been postulated that breast cancer surgery performed during the follicular phase of the menstrual cycle is associated with poorer outcome. PATIENTS AND METHODS: We tested this hypothesis by evaluating disease-free survival (DFS) for 1033 premenopausal patients who received definitive surgery either during the follicular phase (n = 358) or the luteal phase (n = 675). All patients were enrolled in a randomized trial conducted between July 1986 and April 1993. All had node positive breast cancer and randomization was stratified by estrogen receptor (ER) status. All patients received at least three cycles of adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). The median follow-up was 60 months. RESULTS: Patients who underwent definitive surgery for breast cancer in the follicular phase had a slightly worse disease-free survival than those operated on during the luteal phase (five-year DFS percentage: 53% versus 58%; hazard ratio, 1.13; 95% confidence interval (CI), 0.94-1.38; P = 0.20). The effect was significantly greater for the subpopulation of 300 patients with ER-negative primaries (P = 0.02 interaction effect; five-year DFS percentages 42% vs. 59%; hazard ratio 1.60; 95% CI, 1.12-2.25; P = 0.008). The effect of timing of surgery diminished for analyses based on lesser surgical procedures, e.g., excisional biopsies. In particular, no effect of timing was observed for fine needle aspiration procedures. CONCLUSIONS: Surgical procedures which are more extensive than a fine needle aspiration biopsy might be associated with worse prognosis if conducted during the follicular phase of the menstrual cycle. This phenomenon was seen predominantly for high risk breast cancer with low levels or no estrogen receptors in the primary tumor.

Breast Neoplasms↗
PubMed1996

Impact of adjuvant therapy on quality of life in women with node-positive operable breast cancer. International Breast Cancer Study Group.

BACKGROUND: Adjuvant therapy for early breast cancer is effective but may be toxic. Our aim was to investigate the impact of the presence, timing, and duration of adjuvant chemotherapy on patients' perceptions of their quality of life (QL). METHODS: International Breast Cancer Study Group trial VI assessed adjuvant chemotherapy in 1475 premenopausal and perimenopausal patients, and trial VII assessed adjuvant tamoxifen or chemoendocrine therapy in 1212 postmenopausal patients with node-positive breast cancer. Patients were asked to complete a QL questionnaire-single-item linear analogue self-assessment scales measured physical wellbeing, mood, appetite, and perceived adjustment/coping. QL was assessed in this way at the beginning of treatment, 2 months after the start of treatment, every 3 months, and at 1 and 6 months after recurrence. FINDINGS: Baseline QL scores decreased as the number of involved axillary nodes increased (for example, mean mood score: 66.1 for women with one positive node, 66.4 for two to four positive nodes, 61.3 for five to nine positive nodes, and 59.1 for ten or more positive nodes; p = 0.008 for trends), and were lower in patients with oestrogen-receptor-negative than in patients with oestrogen-receptor-positive tumours (61.4 vs 66.3, p = 0.0009). All treatment groups showed substantial improvement in QL scores during adjuvant therapy. Patterns of QL scores reflected presence, duration, and timing of cytotoxic treatment. Longer initial cytotoxic therapy delayed improvement in QL scores. Later cytotoxic therapy had transient adverse effects. Anticipation of future therapy also affected QL scores. INTERPRETATION: Overall, chemotherapy had a measurable adverse effect on QL, but this effect was transient and minor compared with patients' adaptation/coping after diagnosis and surgery. This finding should encourage patients and doctors to choose appropriate adjuvant therapy with less concern for initial toxicity.

Antineoplastic Agents, Hormonal↗
PubMed1996

[Conservative surgery in the environment of a screening program for breast carcinoma: evaluation of the results in terms of local recurrence].

This report evaluates the results of conservative surgery plus radiotherapy (QUART) in a group of 123 patients from the screening programme of the District Health Board USSL 41 in Brescia, Italy (over 250 tumours diagnosed in two screening rounds, between 1987 and 1993). To date no recurrence of neoplasms in the operated breast have been diagnosed in either of the two QUART groups (64 patients from the first round, average follow-up 28 months, median 66 months; 59 patients from the second round, average follow-up 28 months, median 30 months). A new carcinoma in the contralateral breast occurred in 3 patients (2 from the first and 1 from the second round), while in 3 cases there was a recurrence in another site (2 from the first and 1 from the second round). These results confirm both the proven effectiveness of conservative treatment in the local control of breast tumours, and the importance of the correct choice of conservative treatment in optimising aesthetic and therapeutic results.

Breast Neoplasms↗
PubMed1993

MICE: a new active combination for non-small cell lung cancer.

We have treated 38 patients with stage III/IV non-small cell lung cancer with the following regimen: mitomycin-C = 6 mg/m2, ifosfamide = 3 g/m2, cisplatin = 75 mg/m2, vindesine = 3 mg/m2 (MICE), intravenously (i.v.) on day 1, every 3 weeks. Among 26 patients with stage IV disease, 15 obtained a partial remission (PR) (response rate = 57%, 95% confidence interval = 38-76), with a median time to disease progression and a median survival of 4.9 and 7.1 months, respectively. 6 out 7 patients with stage IIIA disease were documented as PR and 5 of them underwent radical surgery with two pathologically confirmed complete remissions. Overall toxicity was substantial but manageable: 3 patients had grade III/IV leucopenia (although 5 patients had neutropenic fever) whereas 13 patients experienced grade II/II anaemia. In conclusion we believe that MICE regimen is an interesting combination and warrants further evaluations both for palliation and in a neoadjuvant setting.

Adult↗
PubMed1993

L-folinic acid and 5-fluorouracil in the treatment of advanced breast cancer: a phase II study.

BACKGROUND: The combination of 5-fluorouracil (5-FU) and folinic acid (FA) is an active combination for the treatment of advanced breast cancer (ABC). Theoretically, the biologically active isomer of FA, 1-FA, should be more effective than racemic FA in modulating 5-FU activity. PATIENTS AND METHODS: Thirty-three patients (pts) with ABC, all previously treated with an anthracycline-based combination for advanced disease were treated with 1-FA: 100 mg/m2 i.v. and 5-FU: 370 mg/m2 i.v. for 5 consecutive days every 4 weeks. RESULTS: Three complete remission (CR) and 11 partial remission (PR) were obtained for an overall response rate of 42% (95% CI = 25-59). Median duration of response was 10 months, median survival was 15 months for responders, 11 months for NC and 3 for PD. Eleven pts experienced a WHO grade III-IV oral mucositis (33%), 6 pts had grade III and one grade IV diarrhea, two pts had grade IV neutropenia resulting in one toxic death. CONCLUSIONS: In this heavily pretreated population of pts with ABC, this regimen showed an interesting activity with substantial toxicity. Both the response rate and the pattern of side-effects seem similar to those experienced with the racemic mixture of d,1-FA. Modulated 5-FU warrants an increasing consideration in the treatment of breast cancer.

Adult↗
PubMed1992

Sequential estrogen receptor determinations from primary breast cancer and at relapse: prognostic and therapeutic relevance. The International Breast Cancer Study Group (formerly Ludwig Group).

We retrospectively evaluated 401 selected patients who had estrogen receptor (ER) assays both at primary surgery and at relapse in an accessible site to determine the clinical relevance of the subsequent ER determination. The median time between ER assessments was 27 months (range: 2-122 months). The median follow-up time from diagnosis was 6 years (range: 2-12 years). For patients with ER+ tumors at primary diagnosis, 29% (76/261) had ER- tumors at relapse, while for ER- primaries, the conversion rate was 33% (46/140). Conversions from ER+ to ER- occurred more often when the time interval between assays was less than one year (p = 0.004), while conversions from ER- to ER+ tended to occur late (beyond three years; p = 0.0003). Treatments received between assays (usually adjuvant therapy) had only a slight influence on ER status conversion. Post-relapse survival was poor for patients who had the biopsy accessible recurrence within one year; an expression of the aggressive nature of the disease. Among patients whose accessible relapse was beyond one year, those with ER- primaries who converted to ER+ had a longer survival than those whose recurrence was classified again as ER- (p = 0.006). This group of patients with ER- primaries who recurred beyond one year with an ER+ tumor in an accessible site represented 29% (40/140) of all patients with ER- primaries and had an estimated overall survival rate of more than 60% at 6 years from the accessible relapse. ER determination upon relapse within one year has very little clinical relevance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Mitomycin-C, adriamycin, 5-fluorouracil and leucovorin (L-FAM2) in the treatment of advanced gastric cancer: a phase II study.

Thirty previously untreated patients with advanced measurable gastric cancer were given a combination chemotherapy consisting of 5-fluorouracil, 400 mg/m2, and leucovorin, 200 mg/m2 iv on days 1 to 3, mitomycin-C, 10 mg/m2 on day 1 (every other cycle) and adriamycin, 40 mg/m2 on day 2, repeated every 21 days. The overall response rate was 46% (14/30; 95% confidence limits: 28%-64%) including 4 patients with a complete remission. Eight patients progressed. Median duration of remission (CR+PR) was 10 months, with a median survival of 13, 8 and 4 months for CR+PR, NC and PD, respectively. Main toxicities were leukopenia (WHO grade III-IV in 36% of the patients) and alopecia. One patient died from myocardial infarction after an adriamycin cumulative dose of 480 mg/m2. No other treatment-related death occurred. L-FAM2 is an effective combination for advanced gastric carcinoma. Further studies based on the association of leucovorin and 5-fluorouracil in combination with other active drugs are warranted.

Adult↗
PubMed1991

Fluorouracil, high-dose folinic acid, low-dose alpha-2b interferon and dipyridamole in the treatment of advanced colorectal cancer. A pilot study.

Twenty-six patients with advanced colorectal cancer were treated with a combination based on multimodal biochemical modulation of 5-fluorouracil by means of high dose folinic acid, low-dose alpha-2b interferon and dipyridamole. The overall response rate was 42% (95% confidence intervals = 23%. 61%) with four complete remissions (15%). The median duration of response was 9 months and the median survival for responders was 15 months (all patients = 12 months). Toxic side effects included oral mucositis (grade III-IV = 38%) and a generally mild flu-like syndrome. This regimen seems active and safe enough to be compared with the combination of fluorouracil and high-dose folinic acid.

Adult↗
PubMed1990

Mitomycin-C, vinblastine, and lonidamine as salvage treatment of advanced breast cancer. A pilot study.

Thirty-two patients with advanced breast cancer were treated with mitomycin-C 10 mg/m2 IV and vinblastine 6 mg/m2 IV every 21 days in combination with lonidamine 450 mg/day P.O. and prednisone 15 mg/day P.O. given continuously. Among the 29 evaluable patients (all but three pretreated with an anthracycline-based regimen), one complete remission (CR) and six partial remissions (PR) (response rate, 24%) were seen. The median duration of response was 14 months (range, 4-30 months). Median survival for responders was 18 months (range, 4-30 months). Hematological toxicity was uncommon; the main lonidamine-related side effects were myalgia, abdominal cramps, and reversible deafness; these side effects were severe in two, one, and one patients, respectively. The regimen seems to have a reasonable degree of activity and toxicity in advanced, refractory breast cancer. The role of lonidamine in the treatment of this disease warrants further evaluation.

Adult↗
PubMed1989

Cyclophosphamide, epirubicin, high-dose folinic acid and 5-fluorouracil (super-FEC) as first-line chemotherapy for advanced breast cancer: preliminary results.

Forty patients with metastatic breast cancer were treated with a new combination regimen consisting of cyclophosphamide, epirubicin, high-dose folinic acid and 5-fluorouracil (super-FEC). A major objective response was observed in 32 patients (80%). Among these, 11 patients (27%) experienced a complete remission. The median duration of response was 10+ and 12+ months for CR and PR, respectively. The most common side-effect was oral mucositis (Grade III = nine patients; grade IV = two patients), while haematological toxicity was virtually absent. Considering the high-risk characteristics of the vast majority of the enrolled patients (75% had dominant visceral disease), these preliminary results suggest that super-FEC has a powerful activity in poor-prognosis metastatic breast cancer with an acceptable degree of toxicity.

Adult↗
PubMed1989

5-Fluorouracil and dipyridamole in metastatic breast cancer: a pilot study.

In an attempt to increase the clinical activity of 5-fluorouracil (5-FU) by blocking the thymidine salvage pathway, 15 patients with refractory metastatic breast cancer (MBC) were treated with oral dipyridamole (D): 75 mg p.o. q.i.d. and 5-FU: 400 mg/m2 i.v. by bolus for 5 consecutive days, every 28 days. All the patients were pretreated with 5-FU and an anthracycline-based regimen. Toxicity was minimal, with 8 patients experiencing a D-related moderate headache. Although no objective responses were seen, two patients with 5-FU refractory disease showed tumor shrinkage. A different D schedule and the addition of folinic acid (FA) to 5-FU might provide better results and deserves further evaluation.

Adult↗
PubMed1989

Phase II trial of 5-fluorouracil and high-dose folinic acid in advanced renal cell cancer.

Fourteen patients with metastatic renal cell carcinoma (RCC) were treated with high-dose folinic acid (HDFA): 200 mg/m2 i.v. and 5-fluorouracil (5-FU): 370 mg/m2 i.v. for 5 consecutive days every 28 days. Severe oral mucositis (WHO grade III-IV) was experienced by two patients, whereas hematological toxicity was mild. No complete or partial remission was observed. Short-lasting stable disease occurred in 8 patients (median = 5 months, range 2-11). This combination does not need further evaluation in patients with RCC.

Adult↗
PubMed1988

Premarin priming before prednimustine, high-dose folinic acid and 5-fluorouracil as salvage chemotherapy for advanced breast cancer.

Thirty patients with advanced and mainly pretreated breast cancer were treated with a combination of premarin, prednimustine, high-dose folinic acid and 5-fluorouracil. Among the 30 evaluable patients, 9 (30%) achieved an objective response (median duration: 9 months). Oral mucositis was the limiting toxicity, while myelosuppression was quite mild. In spite of considerable activity as salvage regimen, these results do not seem better than those achieved in our Institute with high-dose folinic acid and 5-fluorouracil alone.

Breast Neoplasms↗
PubMed1988

Complete estrogen blockade with buserelin and aminoglutethimide for advanced breast cancer: a phase I-II study with long-term hormonal correlations.

We treated 21 patients with advanced breast cancer with buserelin, aminoglutethimide and cortisone acetate in an attempt to obtain a complete estrogen blockade both in premenopausal and postmenopausal patients. Ten patients (47%) obtained an objective response without any relevant side-effects. Dealing with hormonal data, it must be outlined that serum testosterone levels decreased significantly in postmenopausal patients, suggesting a possible explanation for the activity of luteinizing hormone-releasing hormone analogue in this group of patients.

Adult↗