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M Zambetti

Publications and source records attributed to M Zambetti.

49 records · Page 3Linked to original sources
PubMed1988

Timing of surgery and the role of cytoreductive chemotherapy in patients with advanced ovarian carcinoma.

We retrospectively selected 27 consecutive patients with advanced ovarian carcinoma (15 stage III, 11 stage IV and 1 relapse) who had an unresectable intraabdominal tumor at presentation and prospectively evaluated the overall treatment outcome. Patients were initially treated with chemotherapy consisting of cisplatin-containing regimens in 20 cases, adriamycin and cyclophosphamide in 5, and melphalan in 2. Treatment was continued until maximal tumor response or progression. Following a median of 6 cycles of chemotherapy, all patients underwent debulking surgery. Six women were without evidence of disease and 13 had minimal residual disease after surgery, for an overall 70% rate of optimal debulking. Patients with evidence of disease at laparotomy were treated with 5 additional cycles of chemotherapy, and response was then assessed at laparotomy except for patients with progressive disease. Nine (33%) patients were pathologic complete responders at the end of the entire treatment program. Overall median survival time was 26 months, with a median relapse-free survival of 33 months. Tumor responses were not associated with any particular chemotherapy regimen. The results achieved in this series of patients together with the data from the literature suggests that use of a cytoreductive chemotherapy of short duration has the potential of increasing the rate of optimal debulking surgery. Furthermore, it may contribute to a better disease control in women with bulky ovarian carcinoma compared to the present strategy, which consists of surgery followed by chemotherapy.

Combined Modality Therapy↗
PubMed1988

Hormonal changes induced by the pure antiandrogen flutamide in postmenopausal women with advanced breast cancer.

Hormonal changes induced by the pure antiandrogen flutamide were studied in three postmenopausal metastatic breast cancer patients. The drug was administered at a dose of 250 mg, three times a day for 3-6 months. In each patient a sharp decrease of about 50% was observed in the circulating levels of DHT and DHEAS, irrespective of pretreatment values. A concomitant, although less pronounced, reduction in circulating testosterone, androstenedione and estradiol was found. A decrease in circulating steroids was associated with a 30% decrease in SHBG concentrations in two patients; in the third patient a 30% increase occurred. Androgens in urine, namely testosterone, androstanediol and 17-KS, decreased accordingly. In addition, a marked decrease in 17-OHCS occurred in two of the patients. These data indicate that flutamide is an effective antiandrogen in women and suggest two possible mechanisms by which the drug exerts its antiandrogenic activity: (a) inhibition of conversion of testosterone into the more active DHT, and (b) inhibition of synthesis of the adrenal precursors of active androgens. Minor variations in circulating LH and FSH were observed. Pretreatment prolactin values, which were higher than normal, dramatically decreased by 90% in one patient who had a partial remission of her disease, and they further increased in another patient who relapsed while on therapy.

Anilides↗
PubMed1987

Aminoglutethimide in postmenopausal breast cancer refractory to multiple hormonal and cytostatic treatments.

Eighty-seven consecutive patients with metastatic breast cancer were treated with aminoglutethimide plus hydrocortisone. All patients were postmenopausal and had progressive disease following prior chemotherapy and endocrine therapy. Eighty-five women were evaluable for drug response. One patient showed complete remission and 14 patients partial response, for an overall response rate of 17%. The median duration of response was 11+ months. The response rate was highest in the presence of soft tissue involvement (36%). The most common side effects were transient skin rash, lethargy, and dizziness. Two patients discontinued treatment because of cutaneous allergy. Aminoglutethimide can be considered a moderately active agent when utilized as second- or third-line hormonal therapy.

Adrenalectomy↗
PubMed1987

Adjuvant chemotherapy after conservative surgery plus irradiation versus modified radical mastectomy. Analysis of drug dosing and toxicity.

In a cohort of 764 evaluable patients with primary breast cancer, we have compared the ability to deliver full doses of adjuvant chemotherapy in two patient groups: one undergoing conservative breast surgery plus irradiation and the other having modified radical mastectomy as primary treatment for the cancer. We have also analyzed the toxicities of the concurrent radiation and chemotherapy. The group having irradiation had significantly more moderate leucopenia, which caused a short delay (median, three weeks) in the overall time necessary to complete the planned chemotherapy. However, among those patients who completed the planned chemotherapy cycles, the fraction who received more than 85 percent average drug doses was 96 percent or higher in all but one small subgroup. Interaction between the irradiation and chemotherapy caused mild breast skin reactions in 42 percent of patients so analyzed and worse reactions in 12 percent. When follow-up tracings were performed, mild electrocardiogram abnormalities occurred in 19 percent of patients, apparently because of the irradiation. We conclude that intravenous adjuvant chemotherapy, as administered in this study, can be delivered as intensely with conservative primary treatment as after mastectomy and that toxicity is mild, rarely requiring intervention or treatment discontinuation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Current status of Milan adjuvant chemotherapy trials for node-positive and node-negative breast cancer.

This report summarizes the most important clinical results achieved at the Milan Cancer Institute through various randomized trials with systemic adjuvant chemotherapy. In the study testing surgery versus surgery plus 12 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in node-positive patients, the reduction in failure rate (34%) significantly favored CMF-treated patients (P less than 0.001). Despite a reduction in the death rate of 23%, the overall survival showed only a trend for CMF compared to surgery alone (P = 0.10). In a second study, the 8-year results confirmed the lack of difference in relapse-free survival and total survival rates between patients who received 12 and 6 cycles of CMF. The third study indicated that at 6 years, postmenopausal women who had 1-3 positive lymph nodes and were treated with full-dose sequential non-cross-resistant combinations had rates of relapse-free survival and total survival that were superior to those previously achieved with CMF in the same menopausal subset. In a limited series of patients with negative axillary nodes as well as negative estrogen receptors, there was clear evidence of very poor prognosis in women given only local-regional therapy, compared to women treated with adjuvant CMF. Within the node-negative subset, the proliferative activity (labeling index) of the primary tumor appears to be a more effective prognostic discriminant than estrogen receptor status. The proportion of primary drug-resistant tumor cells as well as the lack of relative dose intensity in the drug programs tested so far probably represent the two most important causes for the failure of adjuvant chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Antiemetic activity of metoclopramide versus alizapride during cancer chemotherapy.

A prospective randomized study was conducted to compare the antiemetic efficacy of metoclopramide (MCP) versus its recent derivative alizapride (ALZ) in patients undergoing cancer chemotherapy. Both drugs were given at a dose of 2 mg/kg i.v. push for 5 doses. A positive response was defined as absence of nausea or emesis, or moderate nausea with one or two emeses per day. Eighty-two patients were evaluable. Forty-two received MCP and 40 received ALZ. A positive response was observed in 54% MCP-treated and 41% ALZ-treated patients. Neurologic toxicity, mainly extrapyramidal disturbances, was the most remarkable adverse side effect; it occurred more frequently in the MCP-treated group (31%) than in the ALZ-treated group (17%). Both drugs were found to be more effective in previously untreated patients and when employed together with steroids. MCP was more effective (52% positive response) than ALZ (41% positive response) in cisplatin-treated patients. To better control drug-induced vomiting, we believe that future trials should evaluate slow i.v. infusion of antiemetic agents and their combination with dexamethasone.

Adolescent↗
PubMed1985

Accuracy of the double contrast enema in evaluation of the abdominal diffusion of ovarian carcinoma.

The results of 103 double contrast enemas in 72 patients with ovarian carcinoma (stage III and IV) were compared with laparoscopic and/or laparotomic findings at comparable times. The evaluation of the validity of radiology in detecting the presence of abdominal disease showed an 84% overall accuracy, 75% specificity and 86% sensitivity. The accuracy in detecting signs of adhesion and parietal infiltration of the large bowel was 76.3%, due to the limited size of most of the lesions. Forty-seven of the 72 patients underwent a double contrast enema and laparoscopy during presurgical staging: accuracy in detecting lesions was the same for both examinations (80.4%). When double contrast enema and laparoscopy were used together in the evaluation of abdominal extension of the disease, the diagnostic accuracy rose to 93.6%.

Abdominal Neoplasms↗
PubMed1985

Ten-year experience with CMF-based adjuvant chemotherapy in resectable breast cancer.

The paper reviews all adjuvant studies carried out since 1973 at the Milan Cancer Institute in women with resectable breast cancer and positive axillary nodes. The updated results essentially confirm previous findings, and indicate that CMF-based chemotherapy is able to exert a prolonged therapeutic activity in a fraction of patients bearing micrometastases. In particular, the first randomized study testing no postoperative chemotherapy vs 12 CMF cycles, showed a 10-year relapse free survival (RFS) of 31.4% vs 43.4% (P less than 0.001) and an overall survival (OS) of 47.3% vs 55.2% (P = 0.10), respectively. Findings related to subsets indicated that RFS and OS benefit was significant in premenopausal and not in postmenopausal women, and in both treatment groups the observed findings were always related to the number of histologically positive nodes. On relapse, salvage therapy administered to controls failed to produce superior results compared to those achieved in the CMF group. The 8-year results of the second study testing 12 vs 6 CMF cycles failed to show a significant difference between the two treatment groups. This indicated that the maximum tumor cell kill occurred during initial chemotherapy cycles. In the third study, carried out only in postmenopausal women less than or equal to 65 years, sequential non-cross resistant combinations (CMFP----AV) at full dose achieved superior results compared to CMF in the subset with limited nodal extent. Acute side effects were moderate and no delayed morbidity, including increased incidence of second neoplasms, was observed. We conclude that the tumor cell heterogeneity, and in particular primary drug resistance, represents the major obstacle to adjuvant systemic therapy in high risk breast cancer. Current results suggest that 6 cycles of CMF can be considered a simple, safe, and moderately effective adjuvant therapy. Future trials should contemplate treatments of different intensity related to major prognostic subsets, while in women at very high risk of early relapse more vigorous drug regimens should be concentrated within the first six months from local-regional therapy.

Adult↗
PubMedDate not supplied

T3b-T4 breast cancer: factors affecting results in combined modality treatments.

Two hundred and seventy-seven consecutive patients with T3b-T4 breast cancer referred to the Milan Cancer Institute between 1973 and 1980 were treated with a combined modality approach. Chemotherapy (CT) consisted of AV, i.e. adriamycin (60-75 mg/m2 day 1) and vincristine (1.2 mg/m2 days 1 and 8) and was given for three to four cycles prior to local regional modality. Local-regional treatment consisted of either radiotherapy (RT) in 198 patients or surgery (S) in 79 women. Additional chemotherapy was then administered to a total of 205 patients. In the absence of distant metastases, frequency of good local control was significantly inferior in patients given CT + RT (63.9 per cent) compared to those treated with CT + RT + CT (75.4 per cent) and CT + S + CT (82.3 per cent, P = 0.033). Also freedom from progression (FFP) and overall survival (SURV) were significantly superior in the groups receiving more prolonged chemotherapy treatment compared to patients treated with CT + RT (FFP: P less than 0.0001; SURV: P = 0.002). None of the variables examined was able to affect the response rate, while axillary nodal status and tumor size played a major role in the duration of FFP and SURV. Our findings indicate that a more aggressive treatment is needed to improve current results in this stage of disease. To overcome the problem of local-regional recurrence, treatment should probably begin with cytoreductive surgery followed by postoperative radiotherapy in all patients with the exception of those having inflammatory carcinoma. Systemic treatment should then be delivered to control distant micrometastases.

Adult↗
PubMedDate not supplied

Locally advanced breast cancer treated with primary chemotherapy: comparison between magnetic resonance imaging and pathologic evaluation of residual disease.

AIMS AND BACKGROUND: We evaluated the response of locally advanced breast cancer to induction chemotherapy using MRI techniques. The size and vitality of any residual pathologic tissue was quantified by means of morphologic and dynamic analysis. A curve derived from the dynamic parameters shows the uptake intensity with respect to the time elapsed since administration, which is related to vascularization and therefore indirectly reflects the angiogenesis of malignant tissue. METHODS AND STUDY DESIGN: A group of 30 patients were examined with MRI for staging purposes before undergoing treatment and subsequently to assess the response to treatment. Alterations in size and dynamic parameters were closely monitored. RESULTS: The overall accuracy was 90%, the sensitivity 96%, the specificity 75%, the positive predictive value 92.5% and the negative predictive value 66%. Interestingly, analysis of the dynamic curves made it possible to obtain additional information regarding the angiogenetic activity of the residual tumor. CONCLUSIONS: Evaluation of the response to treatment by means of conventional imaging and clinical examination can be particularly difficult because of the fibrosis induced by cytotoxic drugs or the small volume of residual disease. The additional information supplied by MRI could therefore allow a more conservative surgical approach in selected cases of optimal response to treatment, as well as a much more accurate follow-up. Furthermore, the variation in dynamic parameters according to the vitality of residual disease could in the future become a useful tool for monitoring the effectiveness of anti-angiogenetic drugs.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Detection of Lewis(a) antigen in sera of ovarian carcinoma patients by MOv2-MOv8 double-determinant radioimmunoassay.

The monoclonal antibodies MOv2 and MOv8, raised against ovarian carcinoma, were found to be directed against two non-crossreacting epitopes expressed on the same molecule. Immunochemical analysis of the MOv8 recognized epitope showed that the Le(a) oligosaccharide, or commercial anti-Le(a) MAb, but not the anti-Le(b) MAb, prevented Ov8 binding to the reference target cell line (SW626), indicating that it is carried by the Le(a) antigen. Since we previously reported that MOv2 also recognises the Le(a) antigen, these data suggest that Mov8 and Mov2 were directed against different epitopes on the same oligosaccharide chain. Bearing in mind the knowledge of the biochemical nature of the monoclonal antibody recognized epitopes (CaMOv2 and CaMOv8), the presence of the circulating molecules recognized by them was analyzed by double determinant immunoradiometric assay (DDIRMA) in 103 sera from ovarian carcinoma patients. Patients with clinical evidence of the disease (ED) with MOv2 and MOv8 reactive and negative tumors had sera reactivity in 67% and 19% respectively. Also, 26% of the patients with no clinical evidence of disease (NED) had positive sera. When we investigated the relationship between MOv2-MOv8 DDIRMA sera positivity and red blood cells (RBC) Lewis phenotype, a strong correlation was found between the Le(a)+ phenotype and DDIRMA sera reactivity in healthy donors (6/6) and in ovarian carcinoma patients (9/10) whatever their clinical condition. No Le(a)- healthy donors gave evidence of MOv2-MOv8 reactive sera. In contrast, 33% and 57% of the sera from ED carcinoma patients with respectively Lea-b+ and Lea-b- phenotype were positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗