Search PubMed⌕ Search

Biomedical subjects

P Valagussa

Publications and source records attributed to P Valagussa.

At least 109 records · Page 6Linked to original sources
PubMed1989

Cell kinetics as a prognostic indicator in node-negative breast cancer.

The consistency of the prognostic role of cell kinetics (evaluated as the [3H]thymidine labeling index, LI) over a period of years has been assessed in 354 patients with resectable node-negative breast cancer subjected only to Halsted or modified radical mastectomy. The risk of disease recurrence and death was proportional to LI values and the pattern was superimposable, regardless of menopausal status, in the two consecutive case series entered in this retrospective study. In particular, tumors with high LI (greater than 2.8%) had a higher 6-year probability (41% vs. 25%, P less than 0.0001) of manifesting local-regional and distant metastases and of dying (19% vs. 5%, P = 0.0005) as compared to tumors with low LI. In tumors with high LI the risk of relapse within the first 2 years from mastectomy was twofold compared to that of tumors with low LI. Multiple regression analysis showed that LI also retained its prognostic significance in both relapse-free and overall survival when tumor size and estrogen receptor status were considered. The present findings confirm that LI can substantially contribute to the selection of high risk node-negative patients who could be candidates for adjuvant chemotherapy.

Adult↗
PubMed1989

Systemic therapy in resectable breast cancer.

There is now convincing evidence that adjuvant systemic therapy for high-risk breast cancer can significantly reduce tumor mortality at 5 years. The overall treatment benefit for women with node-positive tumors may be considered moderate but clinically important. The most frequent choices of chemotherapy and hormonal therapy are discussed. In patients with node-negative receptor-negative tumors there is preliminary evidence of benefit from adjuvant combination chemotherapy. Primary (neoadjuvant) chemotherapy can allow conservative surgery in most tumors suitable for mastectomy, but this form of treatment remains, at present, experimental. Potential long-term toxicity from systemic adjuvant therapy should be continuously monitored.

Antineoplastic Agents↗
PubMed1988

Adjuvant chemotherapy for breast cancer.

The development of the use of chemotherapy in the treatment of breast cancer is discussed. Its contribution in the primary management of this disease lies not only in the limited but consistent reduction in mortality, but it has helped to elucidate the biological complexity of breast cancer. Also, it has stimulated basic scientists and research physicians to integrate their efforts, which is expected to result in further clinical progress.

Antineoplastic Agents↗
PubMed1988

Combined modality treatment for stage I-II non-Hodgkin's lymphomas: CVP versus BACOP chemotherapy.

This paper reports the 5-year results of a prospective randomized study beginning in 1976 on 177 evaluable patients with pathologic Stage I-IE and II-IIE non-Hodgkin's lymphomas with diffuse histology according to the Rappaport classification. Treatment consisted of either CVP or BACOP chemotherapy (3 cycles) followed by regional radiotherapy (40 to 50 Gy) and further cycles of either combination. In both arms, complete remission at the end of combined treatment was high (CVP 93%, BACOP 98%) regardless of age, stage or bulky disease. At 5 years, the comparative freedom from first progression was 62% for CVP vs 78% for BACOP (p = 0.02), respectively. Clinically relevant differences favoring BACOP chemotherapy were essentially documented in patients with large cell lymphomas (International Working Formulation), those with Stage II having more than three involved anatomical sites, bulky disease and age over 60 years. Recurrence within radiation fields was documented in only 5% of complete responders. Combined treatment was, in general, well tolerated particularly when BACOP was used. In only 2 patients given CVP post radiation cutaneous fibrosis was documented. Second solid tumors were detected in 4 patients. One patient started on CVP died because of brain stem necrosis after 45 Gy. We conclude that in Stage I-II patients with nodal and extranodal diffuse non-Hodgkin's lymphomas, particularly large cell lymphomas, combined modality approach with primary Adriamycin and bleomycin containing regimen, such as BACOP, followed by adjuvant radiotherapy offers high chances of cure with minimal toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Cyclophosphamide, adriamycin, and cis-platinum (CAP) in metastatic and locally advanced breast cancer.

A combination of cyclophosphamide, adriamycin, and cis-platinum (CAP) was tested in 20 previously untreated patients with locally advanced or metastatic breast cancer with the aim of assessing the ability of this platinum-containing regimen to induce a high complete remission rate. The drug regimen was given on a 3/week schedule at the following doses: cyclophosphamide 200 mg/m2 i.v. on days 1, 2, 3; adriamycin 40 mg/m2 i.v. or day 1 and cis-platinum 20 mg/m2 i.v. plus hydration on days 1, 2, 3. In the absence of progression, six cycles of CAP were planned and response was evaluated at that time. Thirteen of 20 patients achieved partial remission (65%) but only one obtained complete remission (5%). Overall median duration of response was 9 months (range 4-20 + months). Tumor response was mainly documented in soft tissues (primary tumor: 14 of 16; other sites: 19 of 20). Grade II leukopenia was documented in 60% of patients. All patients experienced moderate to severe gastrointestinal toxicity and alopecia was universal. No renal toxicity was observed. Although CAP regimen at the given dose schedule induced a high overall response rate (70%), the complete remission rate in this limited number of patients was lower than expected. These results do not appear superior to those achieved with conventional drug regimens.

Adult↗
PubMed1988

Treatment strategies for Hodgkin's disease.

Over the past 2 decades, treatment of Hodgkin's disease has evolved considerably through innovations in the management of various stages. The impact of various treatments on the 5-, 10-, and 15-year results is being balanced against delayed morbidity, such as organ damage and second malignancies, produced by the intensity of therapy or the prolonged delivery of given drugs. The results of clinical trials performed during the past decade have allowed us to reconsider the various prognostic variables that can be used in the treatment strategy. The major unfavorable prognostic factors are represented by bulky disease, multiple extranodal sites, systemic B symptoms, age greater than 60 years, lymphocyte-depleted histology, male sex, and progressive disease during chemotherapy. In patients with early disease after surgical staging, the aim of current therapy is to provide a high cure rate within a short period and with limited morbidity. In patients with advanced Hodgkin's disease, the treatment strategy is to achieve durable complete remission in most cases through effective, full-dose, multidrug regimens at the expense of acceptable morbidity. Subtotal or total nodal radiotherapy (RT) induces a 10-year cure rate ranging from 70% to 85% in stages I and II with no bulky lymphoma. In patients with bulky disease and all three systemic symptoms, comparable results can be achieved with primary chemotherapy followed by RT. Currently, stages IIIA and IIIB disease are often managed with combined treatment modalities, although comparable results can be obtained with intensive chemotherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Mitoxantrone: an active agent in refractory non-Hodgkin's lymphomas.

A phase II oriented study with mitoxantrone was undertaken in 31 patients with refractory non-Hodgkin's lymphomas (NHL); 30 patients had evaluable disease. The drug was administered through a 30-min intravenous infusion at the dose of 14 mg/m2 every 3 weeks. A minimum of two cycles were required to define treatment response. Twenty patients were previously treated with Adriamycin whose total dose was not exceeding 300 mg/m2. Complete response (CR) was documented in 9 patients, and partial response (PR), in 5 for a total response rate of 47% (14 of 30). Of 20 patients previously treated with Adriamycin, CR occurred in five and PR in two. The median time to progression was 3 months. Mitoxantrone was well tolerated, and no patient refused treatment. Mild leukopenia was evident in 10 patients and thrombocytopenia in 5 patients. In all cases, electrocardiograms (EKGs) was obtained before each treatment cycle. Systolic time intervals and left ventricular ejection fraction were repeated after 3 cycles and at the end of therapy. Laboratory tests failed to document any major cardiac abnormality. Mitoxantrone is an effective agent in refractory NHL and should be taken into consideration in the design of salvage regimens.

Adult↗
PubMed1987

Four-drug sequential regimen in advanced breast cancer.

The results of two empirically designed and potentially non-cross-resistant combinations administered sequentially in advanced breast cancer with the intent of achieving a high rate of durable complete remissions were analyzed. The two drug combinations consisted of cyclophosphamide plus Adriamycin and high-dose methotrexate plus cisplatin given for a total of three cycles; twenty evaluable patients, not previously treated with chemotherapy, were entered into the study. Ten patients were allocated to receive cyclophosphamide and Adriamycin first followed by high-dose methotrexate and cisplatin, while the remaining patients received the opposite sequence. The overall response rate for the entire group was 85% (17 of 20). However, only three of 20 (15%) patients achieved complete remission. One additional complete response was observed when treatment was prolonged for an additional complete cycle. The overall median duration of response was 13 months (range, 5-20+ months). Responses were similarly distributed among different sites of lesions. Myelosuppression and gastrointestinal toxicity were mild and transient. Reversible acute renal failure was observed after methotrexate administration in three cases. Present results indicate that overall this sequential treatment appears effective in patients with advanced breast cancer. However, the lack of an increased complete remission rate over conventional regimens coupled with a potential risk of renal toxicity prevents further studies with this multiple drug combination.

Adult↗
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↗
PubMed1987

Comparison of different trials of adjuvant chemotherapy in stage II breast cancer using a natural history data base.

Prognostic factors and treatment were analyzed for 2,578 patients to assess the impact of various forms of adjuvant chemotherapy on the natural history of operable stage II (node-positive) breast cancer. The outcome after surgery alone (or with radiotherapy) was determined in 1,014 patients in the natural history data base (NHDB). Adjuvant chemotherapy consisted of L-phenylalanine mustard (L-PAM; 130 patients); cyclophosphamide, methotrexate, and 5-fluorouracil (CMF; 645 patients); doxorubicin and cyclophosphamide (AC; 241 patients); CMF plus vincristine and prednisone (CMFVP; 263 patients); and 5-fluorouracil plus AC (FAC; 285 patients). L-PAM had minimal effect on relapse-free survival (RFS) compared to the NHDB, but all combination chemotherapy programs significantly improved RFS and survival compared to the NHDB. In women with 1-3 positive nodes, all combination chemotherapy programs produced similar results. In women with 4-9 positive nodes, the FAC regimen appeared to be associated with superior RFS compared to other programs, but all were superior to the NHDB. In women with 10 or more positive nodes, FAC was the only regimen associated with improved RFS. The use of a NHDB and known pretreatment characteristics, such as nodal status and tumor size, permits comparison of patients at similar risk of recurrence of breast cancer who have received adjuvant chemotherapy and provides leads for evaluation in future prospective clinical trials.

Adult↗
PubMed1987

Development and use of a natural history data base of breast cancer studies.

Pretreatment information, type of treatment, and longitudinal follow-up on 1,971 patients with operable breast cancer were used to establish a breast cancer natural history data base (NHDB). Data were available for 957 patients with stage I (node-negative) breast cancer and 1,014 stage II (node-positive) patients. In women with negative nodes, information was available on 759 patients treated at the Milan National Cancer Institute and 188 patients treated at the Royal Marsden Hospital. After adjustment for differences in the distribution of patient prognostic factors, relapse-free survival and overall survival were not significantly different. Of the 1,014 node-positive patients, 540 were treated at the Milan National Cancer Institute, 258 at the Royal Marsden, and 216 at the M. D. Anderson Hospital. Relapse-free survival and overall survival did not significantly differ between Milan patients and those treated at the Royal Marsden Hospital. However, M. D. Anderson Hospital patients did have significantly better relapse-free and overall survival. In each institution, outcome was consistently most dependent on the number of involved axillary lymph nodes and tumor size. Also, similar patterns of survival were observed for each of the institutions. The development of an NHDB can be of value in the identification and evaluation of consistency of prognostic factors, permitting improved comparisons between clinical trials. The development of such a natural history data base (NHDB) provides a reference for assessing the impact of different adjuvant chemotherapy programs, and aids in the design of new protocols.

Adult↗
PubMed1987

Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy.

In an attempt to reduce some of the delayed sequelae associated with combined modality therapy in Hodgkin's disease, we randomly tested stages IIB, IIIA, and IIIB MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) v ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine). In 232 previously untreated patients, three cycles of either combination preceded and followed extensive irradiation. The complete remission rate was 80.7% following MOPP and 92.4% following ABVD (P less than .02). The 7-year results indicated that ABVD was superior to MOPP in terms of freedom from progression (80.8% v 62.8%; P less than .002), relapse-free survival (87.7% v 77.2%; P = .06), and overall survival (77.4% v 67.9%; P = .03). Moreover, the comparative iatrogenic morbidity showed that irreversible gonadal dysfunction as well as acute leukemia occurred only in patients subjected to MOPP, while cardiopulmonary studies failed to document significant laboratory differences between the two treatment groups. Present findings indicate that ABVD followed by extensive irradiation represents a valid therapeutic alternative to the widely used alkylating agent-containing regimens plus radiotherapy.

Adult↗
PubMed1987

Second malignancies after CMF for resectable breast cancer.

From June 1973 to May 1978, a total of 845 women with resectable breast cancer and positive axillary nodes were entered into two consecutive randomized studies evaluating adjuvant chemotherapy. All patients were subjected to radical or modified radical mastectomy, none received postoperative radiation, and 666 were administered adjuvant CMF (cyclophosphamide, methotrexate, and fluorouracil). After a median follow-up in excess of 10 years, no cases of acute nonlymphocytic leukemia were detected, but 21 second solid tumors other than contralateral breast carcinoma were documented. The cumulative frequency was 4% +/- 1.9% after surgery alone, and 4.2% +/- 1.03% following adjuvant CMF. No differences were observed between patients aged up to 50 years (surgery, 3.1% +/- 2.2%; CMF, 3.3% +/- 1.3%) or older than 50 years (surgery, 4.5% +/- 2.6%; CMF, 5.2% +/- 1.8%). During the same period, a total of 29 contralateral breast carcinomas were documented for a cumulative frequency of 3.7% +/- 1.7% after surgery alone and of 5.2% +/- 1.4% following adjuvant CMF, respectively. We conclude that, at present, there is no evidence for an increased risk of second malignancies following adjuvant CMF as given in this series. Our findings would suggest that second tumors documented so far cannot be entirely ascribed to treatment with adjuvant chemotherapy, but they could be due to a chance association.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Cell kinetics as a prognostic marker in locally advanced breast cancer.

The study analyzes the prognostic implication of cell kinetics on 52 locally advanced breast cancers. All patients were subjected to a multimodal treatment, including primary chemotherapy with doxorubicin and vincristine, surgery, or radiotherapy followed by additional chemotherapy with the same drug regimen. Pretreatment labeling index (LI) is not related to response to primary chemotherapy, whereas it provides information on the course of the disease. In fact, high LI significantly predicts a higher progression rate at the end of the entire combined treatment, a shorter time to disease progression, and a poorer probability of 4-year survival in comparison to low LI. From the present findings, LI appears to be a useful tool to select women with locally advanced breast cancer that would require very aggressive treatment.

Breast Neoplasms↗