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M Zambetti

Publications and source records attributed to M Zambetti.

At least 37 records · Page 2Linked to original sources
PubMed1994

Local recurrences following mastectomy: support for the concept of tumor dormancy.

BACKGROUND: Local or regional recurrence of breast cancer occurs in 5%-30% of patients treated by Halsted radical or modified radical mastectomy. Lag time between treatment and recurrence varies widely, and it is not known whether the recurring tumor grows at a constant growth rate or at a more rapid rate after a period of tumor dormancy. PURPOSE: This study was undertaken to discriminate between the above-mentioned hypotheses, i.e., determine whether a tumor that recurs after mastectomy grows at a constant rate or whether it grows rapidly following a period of tumor dormancy. METHODS: A series of 122 patients with local recurrence as a first event after mastectomy for resectable breast cancer was evaluated. We measured the diameter of the recurring tumor (Dr) in each patient and calculated the diameter that the recurring tumor could have reached at the immediately preceding physical examination (Dpe), when no local relapse had yet been detected, by assuming an exponential growth during the treatment-free interval. For patients who had a calculated diameter Dpe that was large enough to have been detected at the previous examination, we assumed that a tumor 5 mm in diameter had been mistakenly missed, and the expected corresponding tumor diameter at the time of detection (Drc) was calculated. Finally, the minimum growth rate (mGR) consistent with the sequence "no detection-->recurrence of diameter Dr" was obtained by assuming an exponential growth from the tumor volume corresponding to a diameter 1 mm less than the diameter detection threshold. RESULTS: A wide overlap between Dr and Dpe values was observed. Seventy-two (59%) of 122 Dpe values were larger than the minimum Dr; 18 (15%) were even larger than the median Dr value. The difference between expected and observed detection rates was highly significant (P < .0001). Furthermore, when treatment-free intervals were longer than 4 years, the difference between median Dr and median Dpe values failed to reach statistical significance. The Drc values were significantly lower than the related Dr values, while the mGR values were significantly higher than the corresponding growth rates (paired sample t test: P < .001). CONCLUSION: This study provides evidence that the hypothesis of uninterrupted constant growth of locally recurring breast tumors should be rejected, as it implies a statistically significant departure from observed data. Our results suggest that a period of tumor dormancy followed by more rapid growth could provide an alternative and more reasonable description of tumor recurrence.

Adult↗
PubMed1994

Cardiac effects following adjuvant chemotherapy and breast irradiation in operable breast cancer.

AIM: To assess the frequency and type of cardiac effects in women treated with adjuvant chemotherapy with or without breast irradiation for operable breast cancer. PATIENTS AND METHODS: Retrospective analysis of a series of 825 women taking part in prospectively randomized trials on adjuvant chemotherapy with or without adriamycin (doxorubicin; Farmitalia-Carlo Erba, Milan, Italy) for operable breast cancer at high risk of new disease manifestations. A total of 360 patients (44%) also received breast irradiation because of conservative surgery. Median follow-up in first clinical complete remission from end of all adjuvant treatments was 80 months. According to the protocol requirements, electrocardiograms were obtained before breast cancer surgery, before starting therapy with adriamycin and at the end of all adjuvant treatments. During the follow-up observation, electrocardiograms were systematically obtained at least once a year. In the presence of suspicious findings as well as of clinical symptoms and signs of cardiovascular disease, additional cardiac investigations were undertaken. However, percutaneous endomyocardial biopsies were never performed. RESULTS: Congestive heart failure occurred in a total of 4 women (0.5% of all patients; 0.8% following adriamycin-containing chemotherapy; 2.6% after both adriamycin and irradiation to the left breast), in two of whom it was fatal. ST-segment and T-wave abnormalities in the absence of other symptoms and signs were detected in 3.4% of the case series. Other cardiac events were documented in 6.8% of all patients Overall, cardiac effects were more frequently detected in women who received irradiation to the left breast. In addition, age greater than 55 years at surgery and history of risk factors were important risk modifiers in the occurrence of cardiac events. CONCLUSIONS: The addition of full-dose adriamycin to alkylating-containing adjuvant chemotherapy, as given in our studies, failed per se to increase the frequency of cardiac effects. Thus anthracyclines, which have the potential to improve current treatment results, deserve a proper place in the design of future adjuvant studies.

Adult↗
PubMed1994

Second malignancies following CMF-based adjuvant chemotherapy in resectable breast cancer.

BACKGROUND: Only a few studies have evaluated the long-term effects of adjuvant chemotherapy for breast cancer. Furthermore, neither the relation between the risk of second malignancies and type of adjuvant regimen utilized nor the interaction between chemotherapy and breast irradiation or age of the patients have been described in detail. METHODS: A total of 2,465 patients entered into prospective studies of CMF-based adjuvant chemotherapy carried out at the Milan Cancer Institute between June 1973 and July 1990 were evaluated. The median follow-up was 12.0 years and detailed information about therapy was available for all patients. RESULTS: At 15 years, the cumulative actuarial risk of second malignancies (excluding contralateral breast cancer and basal skin cancer) was 6.7% +/- 0.8% for the total series. The figures were 8.4% +/- 2.9% after local-regional treatment alone, 6.4% +/- 0.9% following CMF, and 5.1% +/- 1.0% following CMF plus Adriamycin (doxorubicin; Farmitalia-Carlo Erba, Milan, Italy). Compared to the general female population, the relative risk following CMF-based adjuvant chemotherapy was 1.29. Three patients, all of whom had received CMF-based chemotherapy, developed acute non-lymphocytic leukemia (cumulative risk 0.23% +/- 0.15%; relative risk 2.3). No differences were evident when breast irradiation was considered, but the cumulative risk of second tumors was slightly higher in women aged > or = 50 years at surgery (7.7% +/- 1.3%) than in younger patients (6.0% +/- 1.0%). CONCLUSIONS: At present, there is no evidence of a significantly increased risk of second malignancies following adjuvant CMF-based chemotherapy such as the one given in this case series. A low risk of acute leukemia was associated with the cumulative total dose of cyclophosphamide administered, and breast irradiation did not enhance this risk. IMPLICATIONS: Our findings suggest that there is no reason to omit alkylating agents from short-term effective adjuvant chemotherapy.

Actuarial Analysis↗
PubMed1992

Nondysgerminomatous tumors of the ovary treated with cisplatin, vinblastine, and bleomycin: long-term results.

Twenty-four consecutive patients with nondysgerminomatous germ cell tumor of the ovary were treated after surgery with cisplatin, vinblastine, and bleomycin (PVB regimen). The cycle was repeated every 3 weeks for three to five courses. Fourteen patients had endodermal sinus tumor, and 10 had mixed germ cell tumors. Stage of disease (FIGO, 1986) was as follows: stage I, 6; stage IIc-IV, 17; and recurrence, 1 patient. All patients were monitored by alpha-fetoprotein and human chorionic gonadotropin. Only 1 patient had received previous chemotherapy. All 5 patients without residual disease and with negative marker levels in which PVB was used as adjuvant treatment were free of disease for a median duration of 59 months from the start of PVB. Of the 19 patients with measurable disease (evident disease or positive marker levels), complete remission was obtained in 16 (84%), but 5 of these relapsed. Therefore, treatment with PVB failed in 8 out of 19 patients (42%) with measurable disease. Toxicity was evident, but no patient died of it. Menses were regular in 11 patients whose initial surgery was conservative. PVB regimen is an effective but not a satisfactory treatment. The considerable failure rate of PVB treatment suggests the investigation of other regimens.

Adolescent↗
PubMed1992

Adjuvant CMF for node-negative and estrogen receptor-negative breast cancer patients.

From December 1980 to September 1985, a total of 90 eligible patients with stage T1-3a, node-negative, and estrogen receptor-negative (less than or equal to 10 fmol/mg of cytosol protein) tumors were entered into a randomized study to assess the effectiveness of adjuvant intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) in a subset of patients at high risk of early disease relapse. High values of [3H]thymidine labeling index were documented in two thirds of 62 assessed specimens from the patient population, and one half of the patients had histologically undifferentiated tumors. Patients were allocated to either local-regional modality alone (control group, 45 women) or to CMF (45 patients) after surgery. A full dose of CMF (600 mg/m2 each of cyclophosphamide and fluorouracil, and 40 mg/m2 of methotrexate) was administered IV on day 1, and then repeated every 3 weeks for a total of 12 treatments. After a median follow-up of 80 months, the 7-year results confirmed the superiority of adjuvant CMF compared to local-regional modality alone (relapse-free survival 85% vs 42%, P = .0001; total survival 86% vs 58%, P = .006). A benefit from adjuvant CMF was observed in all subgroups, and the rates of both local-regional and distant failure were decreased. Treatment was fairly well tolerated and devoid of life-threatening toxicity. Present results confirm our previous observation concerning the dismal prognosis of node-negative and estrogen receptor-negative breast cancer patients as well as the beneficial effect of adjuvant chemotherapy in this selected subset.

Adult↗
PubMed1991

Adjuvant chemotherapy with doxorubicin plus cyclophosphamide, methotrexate, and fluorouracil in the treatment of resectable breast cancer with more than three positive axillary nodes.

To improve current adjuvant results in high-risk breast cancer, in February 1982 we activated a prospective randomized trial using both intravenous cyclophosphamide, methotrexate, and fluorouracil (CMF) and Adriamycin (doxorubicin; Farmitalia-Carlo Erba, Milan, Italy) involving patients with resectable mammary carcinoma and more than three positive axillary lymph nodes. The objective of the study was to assess the effectiveness of four courses of Adriamycin followed by eight courses of CMF versus two courses of CMF alternated with one course of Adriamycin for a total of 12 courses. All drug courses were recycled every 3 weeks. Rather than temporarily reducing doses in the event of myelosuppression on the planned day of treatment, drug administration was delayed for 1 to 2 weeks. At a median follow-up of 59 months, treatment outcome was significantly superior for patients who received Adriamycin followed by CMF (Adriamycin----CMF) than for those given alternating regimens (CMF/Adriamycin). The 5-year relapse-free survival was superior post-Adriamycin----CMF (61%) compared with post-CMF/Adriamycin administration (38%; P = .001). The corresponding figures for the 5-year total survival were 78% and 62%, respectively (P = .005). The benefit of Adriamycin----CMF was observed in all patient subsets. Treatment was fairly well tolerated, and we documented only one case of fatal congestive heart failure in a patient who received postoperative irradiation to the left breast in addition to Adriamycin. Present findings indicate that in women with extensive nodal involvement, Adriamycin----CMF yielded superior results compared with CMF/Adriamycin.

Adenocarcinoma↗
PubMed1991

Cyclophosphamide, methotrexate, and fluorouracil with and without doxorubicin in the adjuvant treatment of resectable breast cancer with one to three positive axillary nodes.

In the attempt to improve current adjuvant results in patients with one to three positive axillary lymph nodes, in November 1981 we activated a prospective randomized study to assess the effectiveness of intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) for 12 courses versus CMF for eight courses followed by Adriamycin (doxorubicin; Farmitalia Carlo Erba, Milan, Italy) for four courses. The 5-year results were evaluated in a total of 486 patients entered into the study up to December 1987. CMF chemotherapy was delivered IV for a total of 12 courses when given alone and for eight courses when followed by four courses of Adriamycin. All drugs were recycled every 3 weeks. Rather than temporarily reducing doses, drug administration was delayed for 1 to 2 weeks in the face of myelosuppression on the planned day of treatment. After a median follow-up of 61 months, no significant differences were evident between the treatment groups in terms of relapse-free (CMF 74% v CMF followed by Adriamycin 72%) and total survival (CMF 89% v CMF followed by Adriamycin 86%). Drug treatments were fairly well tolerated and devoid of life-threatening toxicity. Present results, which were not influenced by menopausal status, indicate that Adriamycin given after CMF failed to improve treatment outcome over CMF alone. However, the role of Adriamycin in an adjuvant setting remains to be further clarified. Considering the good 5-year results achieved in this study at the expense of minimal toxicity, full-dose CMF remains, at present, the adjuvant chemotherapy of choice for patients with one to three positive nodes.

Adenocarcinoma↗
PubMed1990

Prognostic factors in locally advanced noninflammatory breast cancer. Long-term results following primary chemotherapy.

Since 1973 we have treated T3b-T4 (stage III) breast cancer with various forms of multidisciplinary approaches through prospective trials. The present report analyses the 10-year results of 277 patients. Primary chemotherapy consisted of adriamycin plus vincristine given for three or four cycles prior to high-energy irradiation or surgery. In 205 of 277 (74%) additional chemotherapy was planned following the local-regional modality. Primary chemotherapy yielded complete plus partial remission in 62% (CR 7%). Long-term freedom from progression and overall survival were significantly improved by the addition of chemotherapy following local-regional treatment (radiotherapy or surgery). Further chemotherapy was able to significantly affect treatment outcome when it was analyzed both singly and in the presence of other prognostic variables. Thus, in our experience, the variables significantly affecting the 10-year results were represented by duration of treatment and tumor cell burden expressed by size of primary malignancy and clinical nodal status. Locally advanced breast cancer appears a pleomorphic disease difficult to control over a long period of time because of its frequent presentation with bulky tumor and the very high risk of disseminated micrometastases. Thus, the management of this stage of disease almost invariably requires a multidisciplinary approach.

Adult↗
PubMed1990

cis-platinum/vinblastine/bleomycin combination chemotherapy in advanced or recurrent granulosa cell tumors of the ovary.

Seven consecutive patients with advanced/recurrent granulosa cell tumors were treated with PVB (cis-platinum, 20 mg/m2, Days 1-5; vinblastine, 6 mg/m2, Days 1 and 2; and bleomycin, 18 mg/m2, Days 2, 9, and 16). The median age at the start of PVB treatment was 53 years (15-57); three patients had stage III disease and four presented with abdominal recurrences. Prior to PVB, all but one patient underwent surgical treatment, and in six patients gross residual disease was documented. No patient received prior chemotherapy or radiotherapy. The median number of PVB cycles was 5. Three complete (one pathologically documented) and one partial response were observed, for an over-all response rate of 66%. Two complete responders were alive without evidence of disease 7 and 26 months from the start of treatment; the remaining patient relapsed at 15 months. Two patients progressed during treatment, and one died because of sepsis in agranulocytosis. Signs of peripheral neurotoxicity were documented in three patients. The present data confirm the therapeutic activity of the PVB regimen in advanced/recurrent granulosa cell tumors, but the cost/benefit ratio should be clearly assessed.

Adolescent↗
PubMed1990

Cisplatin and cyclophosphamide in advanced ovarian carcinoma: activity and toxicity of an ambulatory regimen.

Chemotherapy with cisplatin (CDDP, 90 mg/m2) and cyclophosphamide (CTX, 600 mg/m2) was administered to 54 consecutive patients with advanced epithelial ovarian cancer (37 stage III and 17 stage IV). In 51 patients, surgery was performed prior to chemotherapy. Of the 37 stage III patients, 13 had only minimal residual disease after surgical debulking. The overall response rate was 69%, with 44% patients achieving clinical (cCR; n = 2) or pathological (pCR; n = 20) complete response. Median follow-up and overall survival time was 26 months, and median CR duration was 30 months. CR was achieved in 6 of 14 patients (43%) who were partial responders after five cycles of chemotherapy and had continued treatment for three to five more cycles. Severe bone marrow toxicity or renal function impairment was never observed, but eight patients presented peripheral signs of dose-related neurotoxicity. These findings indicate that CDDP and CTX in combination are an effective treatment for patients with advanced ovarian carcinoma, and can be administered with tolerable toxicity. In selected cases, prolonged chemotherapy administration can result in durable complete remissions.

Adult↗
PubMed1989

Mitomycin C and vinblastine in advanced refractory breast cancer.

A combination of mitomycin C and vinblastine was administered as salvage treatment in 44 patients with heavily pretreated refractory breast cancer. Response rate was 23% (10 of 44) including one complete response of lung metastases. The highest response rate was seen in intrathoracic localizations (45%). Median duration of response was 6.5 months (range, 3+-17+). Treatment was generally well tolerated, and only 25% of patients developed nausea and vomiting. Neurologic toxicity was represented by paresthesia (8 patients) and constipation (one patient). Mild leukopenia was observed in 30 of 172 treatment cycles, but it exceeded grade 2 in only 5 patients. Considering the good compliance of this regimen and the poor prognosis of patients with advanced refractory disease, the combination of mitomycin C plus vinblastine appears to be useful as salvage treatment for metastatic breast cancer.

Adult↗
PubMed1989

First-line chemotherapy with intraperitoneal cisplatin and intravenous cyclophosphamide in ovarian carcinoma. A preliminary report.

Between August 1982 and October 1986, the feasibility and activity of five cycles of intraperitoneal (i.p.) cisplatin (CDDP) (90 mg/m2 in 6 h dwelling) and i.v. cyclophosphamide (600 mg/m2) were studied in 24 previously untreated patients with ovarian carcinoma having small or no residual disease after cytoreductive surgery. Six patients (25%) had local complications requiring catheter removal before the end of therapy. Fifteen of the 21 patients (71%) evaluable for activity achieved or maintained a pathologic complete remission. The median disease-free survival was 29+ months (range 18-58+ months). Three patients with tumor progression (two patients previously without evidence of disease, and one patient with minimal residual disease), and three partial responders were documented by laparotomy at the end of therapy. Two patients who achieved pathologic complete response relapsed at 20 and 36 months. All treatment failures (eight cases, 38%) occurred in the peritoneal cavity. Since patients were selected for having the most favorable tumor characteristics to benefit from i.p. treatment, our findings may cast some doubt on the actual contribution of i.p. CDDP at a dose of 90 mg/m2 in the treatment of patients with ovarian carcinoma and small residual disease in the peritoneal cavity.

Adult↗