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Biomedical subjects

P Valagussa

Publications and source records attributed to P Valagussa.

At least 127 records · Page 7Linked to original sources
PubMed1986

Salvage treatment of patients suffering relapse after adjuvant CMF chemotherapy.

The efficacy of salvage treatments in 243 patients with operable breast cancer and positive axillary nodes who failed during or after adjuvant chemotherapy with CMF (cyclophosphamide, methotrexate and fluorouracil) was analyzed. Results were compared with those achieved in 100 patients who had relapses after radical mastectomy alone (control group). Salvage treatments consisted primarily of endocrine therapy (castration in premenopausal patients and tamoxifen in postmenopausal women) and chemotherapy (CMF or Adriamycin [doxorubicin] regimens). In 20 patients, however, first salvage treatment consisted of local therapy only (i.e., radiation therapy with or without surgery). In women previously treated with adjuvant CMF, complete plus partial remissions after first salvage treatment were 37% with a median duration of 17 months. In the control group, the response rate was 43% with a median duration of 16 months. The findings also indicated that drug-induced amenorrhea did not lower the objective response to salvage castration. In patients failing with a disease-free interval in excess of 12 months from end of adjuvant CMF, retreatment with the same combination was able to induce remission in 52% of the patients. Current data, derived from prospective controlled studies, confirm that, despite relatively high remission rates, all forms of salvage treatment failed to provide, in unselected cases, long-term control of relapsed breast cancer. Most important, prior adjuvant chemotherapy with CMF did not adversely affect results compared to concomitant controls.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Prognostic implication of labeling index versus estrogen receptors and tumor size in node-negative breast cancer.

The paper analyzes the relation among tumor size (T), estrogen receptor (ER) status, and labeling index (LI) and their relative merits in predicting the relapse-free (RFS) and overall survival (OS) in 215 node-negative women with primary breast cancer. All patients were subjected to Halsted or modified radical mastectomy; none received postoperative irradiation or systemic adjuvant therapy. The 5-year RFS was 75.3% and OS 89.0%. When singly tested, LI and ER were able to significantly predict RFS and OS. In contrast, T influenced only RFS but not OS. The multivariate analysis showed that, in the presence of the two other variables, only LI retained its prognostic significance both for time to relapse (p = 0.0044) and survival (p = 0.035). From the present findings, LI appears to be a new important prognostic variable in the selection of high risk patients for whom adjuvant systemic therapy should perhaps be part of their primary treatment.

Axilla↗
PubMed1986

BREASTCAN: an expert system for postoperative breast cancer therapy.

An expert system, named BREASTCAN and designed to assist physicians giving postoperative adjuvant chemotherapy for breast cancer, is described. The system is based on frames, each corresponding to one stage of treatment--either a decision-making stage or a therapeutic stage. The system has been designed to allow fast and easy consultation by general practitioners lacking computer knowledge.

Breast Neoplasms↗
PubMed1986

New anthracycline analogs in advanced breast cancer.

To test the activity and toxicity of new anthracycline analogs, a series of Phase II disease-oriented studies were performed in women with advanced breast cancer previously untreated with doxorubicin. All drugs were administered every 3 weeks, and the doses in mg/m2 were as follows: doxorubicin and epirubicin 75 i.v., esorubicin 35 i.v., idarubicin 13 i.v. and 45 p.o. When epirubicin was tested vs doxorubicin, both response rate (13 of 21 or 62% vs 11 of 21 or 52%) and median response duration (11 months vs 13 months) were comparable. In 24 patients, esorubicin yielded complete plus partial response in 21% with a median duration of 15 months. In 27 patients given idarubicin intravenously the response rate was 11% for 4 months and the corresponding findings when the drug was administered orally to 25 women were 24% for 8 months. Acute toxic manifestations were lower following treatment with all three analogs compared to doxorubicin. Cardiac toxicity, as documented by echocardiography, systolic time interval and left ventricular ejection fraction was virtually absent following therapy with epirubicin and idarubicin. After a median cumulative dose of 600 mg/m2 for doxorubicin-treated women there was a significant fall in LVEF compared to basal values. Similar findings were observed after a median cumulative dose of 210 mg/m2 for esorubicin. We conclude that epirubicin is as effective as doxorubicin but comparatively less toxic when administered at the same dose schedule. At the doses and schedules utilized in this study, esorubicin and idarubicin resulted less active in breast cancer.

Adult↗
PubMed1986

Second acute leukemia and other malignancies following treatment for Hodgkin's disease.

The records of 1,329 patients with Hodgkin's disease admitted from 1965 to 1982 were analyzed to assess the relative frequency of second neoplasms. Within a median follow-up of 9.5 years, a total of 68 new cancers were documented. Nineteen cases of acute nonlymphocytic leukemia, 6 cases of non-Hodgkin's lymphomas, and 43 cases with different types of solid tumors were identified. The overall risk of non-Hodgkin's lymphoma was 1.3% +/- 0.6% and of solid tumors was 8.3% +/- 1.5% when basal cell carcinomas were included and 6.7% +/- 1.4% when basal cell carcinomas were excluded. No cases of leukemia were documented in patients treated with radiation therapy only. The 12-year estimate of leukemia by treatment was as follows: chemotherapy only 1.4% +/- 2.3%; radiation plus MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) 10.2% +/- 5.2%; radiation plus ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine) 0; and radiation plus other drug regimens 4.8% +/- 1.6%. The risk of leukemia was particularly high (15.5% +/- 7.4%) in patients who received salvage MOPP after radiation failure. A positive association was also noted between increasing age and risk of second malignancies, especially leukemia. The incidence of second neoplasms can be markedly decreased by deleting from potentially curative therapy certain drugs such as alkylating agents, procarbazine, and nitrosourea derivatives.

Acute Disease↗
PubMed1986

Alternating non-cross-resistant combination chemotherapy or MOPP in stage IV Hodgkin's disease. A report of 8-year results.

In patients with stage IV Hodgkin's disease mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) was randomly tested against MOPP alternated monthly with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). All 88 evaluable patients had not received chemotherapy and 25 had had a relapse after primary irradiation. The complete remission rate with MOPP/ABVD was 88.9% (40 of 45 patients), and with MOPP, 74.4% (32 of 43 patients). The 8-year results show that MOPP/ABVD was superior to MOPP in terms of freedom from progression (64.6% compared to 35.9%; p less than 0.005), relapse-free survival (72.6% compared to 45.1%; p less than 0.01), total survival (83.9% compared to 63.9%; p less than 0.06), and survival of complete responders (94.8% compared to 77.1%; p = 0.04). The delivery of MOPP/ABVD was not associated with an increased incidence of major toxicity. The early sequential rotation of two equally effective and non-cross-resistant drug combinations can substantially improve the likelihood of cure in patients with Hodgkin's disease.

Adolescent↗
PubMed1986

CCNU, etoposide, and prednimustine (CEP) in refractory Hodgkin's disease.

Starting in February 1980, 58 patients with Hodgkin's disease refractory to both MOPP and ABVD received as third-line chemotherapy a combination of CCNU or lomustine, etoposide, and prednimustine (CEP). Complete response (CR) was achieved in 40% of cases and partial response (PR) in 14%. The median duration of CR was greater than 15 months, and the median survival of complete responders was longer than 24 months. In addition, CEP alternating with ABVD was given to 21 patients refractory to MOPP chemotherapy. In this series, CR was documented in 67% of patients with a median duration of 24+ months and a median survival of 36+ months. Treatment was generally well tolerated, and all acute side effects were reversible. Present findings indicate that CEP is an effective regimen in patients refractory to MOPP and ABVD.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Salvage chemotherapy in Hodgkin's disease irradiation failures: superiority of doxorubicin-containing regimens over MOPP.

One hundred and twenty-two consecutive patients with Hodgkin's disease who relapsed after primary curative irradiation were treated with either MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) or a doxorubicin-containing regimen (ADM-Reg). The main pretreatment characteristics were comparable in the two groups. Complete remission was achieved in 74.6% of patients treated with MOPP (44 of 59) and in 90.5% of those given ADM-Reg (57 of 63). No difference was observed in the incidence of complete remission with regard to the type of ADM-Reg utilized [MABOP (mechlorethamine, doxorubicin, bleomycin, vincristine, and prednisone), 92.9%; ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), 95.6%; and MOPP alternated with ABVD, 84.6%]. The superiority of ADM-Reg versus MOPP was also confirmed in the 7-year analysis of freedom from disease progression (73.2% vs 42.2%), relapse-free survival (81.2% vs 54.3%), and overall survival (80.5% vs 44.4%). Thrombocytopenia was less frequently observed with ADM-Reg (30%), particularly following ABVD (13%), compared to MOPP (73%). The lowest incidence of alopecia occurred in patients given MOPP (15%) or MOPP/ABVD (19%). Acute nonlymphoblastic leukemia was observed in patients treated with MOPP (five of 59) and MABOP (one of 14). The observed findings indicate that in patients failing to respond to primary radiotherapy, salvage regimens containing doxorubicin are more effective than MOPP. Furthermore, combinations devoid of procarbazine and alkylating agents (ABVD) or with less intensive administration of these drugs (MOPP/ABVD) were not associated with secondary leukemia.

Adolescent↗
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

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↗
PubMed1985

The use of historical controls in breast cancer. An assessment in three consecutive trials.

To evaluate the effectiveness of a new therapy some authors suggest the use of a retrospective control group, especially in cancer trials. In this article, by means of data collected in three consecutive randomized clinical trials on breast cancer performed at the Istituto Nazionale Tumori of Milan, the risks of a practice involving use of data from one trial as "historical controls" for the next one were investigated. The comparability between the baseline characteristics of different groups has been examined by resorting to univariate as well as multivariate statistical methods. The results of the final evaluation of the relative effectiveness of the treatments under study have also been investigated, using both randomized concurrent and historical controls. Although the eligibility criteria did not change, some differences between groups of consecutive trials were observed. The results attained by using historical control data, after adjusting for the differential composition in the baseline characteristics, made evident a biased conclusion in favor of the new treatment tested, which, in a historically controlled study, is always the last one. These results appear to be in agreement with those published by Sacks, Chalmers, and Smith (Am J Med 72:233-240, 1982).

Adult↗