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Biomedical subjects

P Valagussa

Publications and source records attributed to P Valagussa.

At least 91 records · Page 5Linked to original sources
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

Alternating versus hybrid MOPP-ABVD in Hodgkin's disease: the Milan experience.

The long-term therapeutic results achieved in a previous randomized study on stage IV Hodgkin's disease confirm the superiority of MOPP monthly alternated with ABVD compared to MOPP alone. To more closely meet the requirements of the Goldie and Coldman hypothesis, we activated a randomized study testing MOPP-ABVD through two different sequences in July 1982. One arm consisted of monthly alternating one cycle of MOPP and one cycle of ABVD; in the other arm, one half cycle of MOPP was alternated with one half cycle of ABVD within a one-month period (hybrid regimen). Each regimen was given to complete remission plus two consolidation cycles (minimum six cycles). After maximal tumor shrinkage, moderate doses of radiotherapy (25-30 Gy) were delivered to the lymphoid region(s) if bulky at the start of chemotherapy. A total of 300 patients with stage IB, IIA bulky, IIB, III (A + B) and IV Hodgkin's disease previously untreated with chemotherapy or failing after extensive irradiation were evaluated. At a median follow-up of five years, alternating and hybrid regimens yielded superimposable treatment outcomes: complete remission 89 versus 88%, freedom from first progression 65 versus 70%; relapse-free survival 72 versus 78%, overall survival 81 versus 80%, respectively. Tumor cell burden expressed as number of involved nodal sites and presence of pulmonary hilus involvement were the prognostic variables able to significantly influence treatment outcome. Conversely, stage, constitutional symptoms, and histology had no impact on the five-year results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Testicular dysfunction in Hodgkin's disease before and after treatment.

Over a 7-year period, semen analysis was performed in 92 male patients with Hodgkin's disease prior to therapy. In 67% of patients semen revealed a decreased chance for fertility (i.e. oligozoospermia, asthenozoospermia and/or teratozoospermia). The mean basal levels of follicle-stimulating hormone (FSH), luteinising hormone, testosterone and prolactin were in the normal range. In 77 patients in complete remission after alternating MOPP/ABVD (mechlorethamine, vincristine, procarbazine, prednisone; doxorubicin, bleomycin, vinblastine, dacarbazine), testicular function was assessed. 87% of patients were azoospermic, 9% had semen abnormalities and only 4% were normospermic. Recovery of spermatogenesis was documented in only 17 of 42 (40%) reassessed patients after a median time of 27 months and was generally not affected by pretreatment sperm quality. After chemotherapy, the mean value of FSH [20.45 (S.E. 1.7) mUI/ml] was significantly superior compared with that of the mean pretreatment values. No difference was documented in the mean testosterone and prolactin values tested before and after treatment. Our findings indicate that, of patients with Hodgkin's disease, about half are affected by hypogonadism before starting chemotherapy. By utilising alternating MOPP/ABVD, persistent testicular dysfunction was documented in half of the patients.

Adolescent↗
PubMed1991

Prolonged disease-free survival after high-dose sequential chemo-radiotherapy and haemopoietic autologous transplantation in poor prognosis Hodgkin's disease.

Although effective in achieving durable remission in selected tumors incurable by conventional-dose chemotherapy, high-dose regimens requiring bone marrow transplantation remain too toxic for widespread use. With the aim to improve the therapeutic index of high-dose therapy, we have developed a novel program whereby several non-cross-resistant agents (including total body irradiation at myeloablative dose) were delivered sequentially rather than concurrently. The regimen has been tested in 25 patients with Hodgkin's disease refractory to primary chemotherapy (MOPP and ABVD) or relapsed within 12 months after first complete remission. The efficacy of the sequential regimen (72% complete response rate, 49% event-free survival and freedom from progression at four years, with a median observation of 3.5 years for patients remaining alive) compares favorably with the activity so far reported for the most effective high-dose regimens. Toxicity was low; no toxic deaths occurred and only three life-threatening adverse events were documented after autografting. The excellent tolerability of the final myeloablative course most likely reflects the speed and completeness of haematologic recovery that followed the use of peripheral blood progenitors as the sole or additional source of myeloid stem cells. The reduction of haematologic toxicity was further emphasized when rhG-CSF was employed to both shorten post-chemotherapy neutropenic intervals and to collect large amounts of peripheral blood stem cells. We expect that the use of growth factors will have a major impact on the therapeutic index of high-dose regimens. This, in turn, will confirm their safety as primary treatment in selected high-risk subsets.

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

Clinically useful measures to assess the effectiveness of treatments: hints for a proper choice with special emphasis on cancer research.

Several absolute and relative measures useful to assess the consequences of treatments in cancer research are presented together with statistical methods suitable for computing the pertinent confidence intervals. The relationship of these measures with the parameters of the regression models commonly used in the analysis of survival data is elaborated upon. Three examples are elaborated, and conditions of interchangeability of the measures are discussed in detail. Finally, suggestions for the choice of the measure most appropriate for a specified data set are given.

Clinical Trials as Topic↗
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

Influence of clinical trials on current treatment strategy for Hodgkin's disease.

This paper critically reviews the prospective randomized trials conducted over the past three decades in Hodgkin's disease of adults. On the basis of current findings, it is difficult to conclude which randomized trials were influential in defining widely accepted treatment strategies or treatment sequencies, as many studies were poorly conceived and/or executed. However, other reasons may have come into play. The treatment decision making of Hodgkin's disease involves a complex mosaic of prognostic factors and therefore of potentially successful treatment options. Although irradiation and chemotherapy are both effective in different stages, their optimal integration in a multi-disciplinary approach remains to be assessed. Over the years, different research philosophies were translated into different study designs for each stage or patient subset, and in some instances multiple treatment approaches represented a confounding factor in the search for true and reliable prognostic variables. Also, by the time a given trial became mature enough to provide meaningful results, other single arm or randomized studies were undertaken, often yielding premature data. Thus, the instability of treatment results from preliminary analyses can influence subsequent trial design and engender perplexity among physicians. Prospective randomized trials remain today the most reliable tool to assess in Hodgkin's disease the cost benefit ratio of given treatments in clearly identifiable prognostic subsets.

Adult↗
PubMed1990

Salvage chemotherapy in Hodgkin's disease. Results in patients relapsing more than twelve months after first complete remission.

Forty-nine patients with Hodgkin's disease who relapsed after a first complete remission of more than 12 months following primary chemotherapy were treated with salvage therapy regimens. A total of 41 patients (84%) achieved complete remission. In particular, complete response was documented in 17 of 19 patients re-treated with the same initial drug combination. The five-year freedom from progression, relapse-free and overall survivals were 51%, 57% and 65%, respectively. In our experience, consolidation radiotherapy following drug-induced remission failed to improve the five-year relapse-free survival. Present findings indicate that about half of patients relapsing after a disease-free interval exceeding 12 months can remain alive and disease-free 5 years after starting salvage chemotherapy.

Adult↗
PubMed1990

3H-thymidine-labeling index as a prognostic indicator in node-positive breast cancer.

The prognostic relevance of 3H-thymidine-labeling index (3H-TdR-LI) was retrospectively evaluated in 523 women with resectable node-positive breast cancer given adjuvant combination chemotherapy consisting of cyclophosphamide, methotrexate, and fluorouracil (CMF) +/- Adriamycin (doxorubicin; Farmitalia, Carlo Ezba, Italy). The 5-year relapse-free survival (RFS) and overall survival (OS) rates were significantly higher for patients with slowly proliferating tumors (3H-TdR-LI less than or equal to 2.8%) compared with rapidly proliferating tumors (RFS, 66% v 50%, P = .0007; OS, 85% v 73%, P = .0012). In the analysis of RFS, 3H-TdR-LI provided prognostic information independent of axillary node involvement, tumor size, and estrogen receptor (ER) status, with an estimated lower hazard ratio compared with the degree of nodal involvement, but equivalent to that of the other indicators. Conversely, nodal involvement was found to interact with 3H-TdR-LI and receptors on survival. Present findings confirm that tumor cell kinetics represents a prognostic indicator also in an adjuvant situation. 3H-TdR-LI can substantially contribute to a more precise definition of high-risk patients within subsets having the traditionally favorable prognostic characteristics.

Analysis of Variance↗
PubMed1989

Hodgkin's disease: the Milan Cancer Institute experience with MOPP and ABVD.

The report includes the essential therapeutic and toxic results following MOPP vs. MOPP/ABVD and MOPP vs. ABVD within a combined modality setting. The findings indicate that in stage IV the alternating regimen is superior to MOPP while in stage IIB-III ABVD plus radiotherapy yielded superior results associated with no treatment-induced sterility and leukemia compared with MOPP plus radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗