RESUMEN
The overview published in 1999 by the Early Breast Cancer Trialist' Cooperative Group demonstrated that systemic therapy after surgical removal of primary breast tumors prolongs both disease-free and overall survival of patients when compared with no systemic therapy, Specifically, both chemotherapy and ovarian ablation in patients aged less than 50 and tamoxifen in those aged 50 or more achieve a reduction of one-fifth to one-fourth in the annual odds of recurrence or death from any cause. The relative effect of different therapies is independent of the stage of the disease, while the absolute benefit depends not only upon the relative effect of treatment but also upon the baseline prognosis of patients. The overview did not report a direct estimation of the effect of combined chemoendocrine adjuvant therapy. Among the effects that may confound the evaluation of chemoendocrine adjuvant therapy are: (a) the possibility of biological interactions between drugs; (b) the presence on tumor cells of steroid hormone receptors; (c) the suppression of ovarian activity induced by chemotherapy in most premenopausal patients; (d) the scheduling of chemotherapy and endocrine therapy. Based on data of the overview, relevant questions are: (i) does the addition of endocrine therapy (tamoxifen dr ovarian ablation) to chemotherapy improve the outcome of premenopausal patients? (ii) does the addition of chemotherapy to tamoxifen improve the outcome of postmenopausal patients? We have reviewed single randomised trials in an attempt to answer these questions. In premenopausal patients, the addition of tamoxifen to chemotherapy probably induces only small advantages. The addition of ovarian ablation to chemotherapy could improve survival. The relationship between oophorectomy and receptor status has not been extensively studied; however, the addition of oophorectomy, like the addition of tamoxifen, to chemotherapy could be cost effective in cases of estrogen receptor-positive tumors. The effect of tamoxifen in association with ovarian ablation, after chemotherapy, has not yet been studied. In postmenopausal patients the addition of chemotherapy to tamoxifen is debated. The role of receptor status seems to be important in these patients. Most studies found that chemotherapy does not significantly increase the effect of tamoxifen in the subgroup of patients with receptor-positive tumors, while it does increase toxicity. On the contrary, the addition of chemotherapy to tamoxifen, in patients with receptor-negative tumors could significantly improve results.
RESUMEN
A multicentric randomized study was conducted to compare the CNF regimen (cyclophosphamide at 600 mg/m2/iv, mitoxantrone at 10 mg/m2/iv, 5-fluorouracil at 600 mg/m2/iv) with the CMF regimen (methotrexate at 40 mg/m2/iv instead of mitoxantrone) administered every 3 weeks to previously untreated locally advanced or metastatic breast cancer patients. In 119 patients evaluable for therapeutic response, complete plus partial response rate was 44% for CNF and 29% for CMF (p>0.05; 95% C.I.: CNF=32%-56%, CMF=18%-40%). No statistically significant difference regarding time to progression, over survival or response to second-line chemotherapy with Epidoxorubicin was observed between the two regimens. Both regimens were well tolerated, but the percent of alopecia and leucopenia was significantly higher in the CNF patient group (31% versus 5% and 18% versus 0%, respectively; p<0.01). In conclusion, CNF was demonstrated to be slightly more toxic but more effective as compared to CMF (global response: 44% versus 29%, respectively). These findings should be taken into consideration when planning future studies of adjuvant chemotherapy.
RESUMEN
We have demonstrated that interferon-alpha 2 recombinant (IFN alpha) inhibits the growth and modulates the expression of the receptor for transferrin (TRF-R) in human epidermoid carcinoma KB cells. Receptor upregulation results in the reconstitution of intracellular iron levels in the IFN alpha-treated cells. Several anti-TRF-R murine monoclonal antibodies (MAbs) have been generated which induce tumor cell growth inhibition through blockade of receptor function. We have evaluated by MTT assay the effect of anti-TRF-R 42/6, E2.3, A27.15 and D65.30 MAbs given in combination with IFN alpha on the growth of human epidermoid carcinoma KB cells. We found that IFN alpha and A27.15 MAb induced a synergistic antiproliferative effect on these cells. These results suggest that IFN alpha may potentiate the antitumor efficacy of TRF-R-targeted therapy.
RESUMEN
Cisplatin and carboplatin are both active in ovarian cancer with different toxicity profiles; thus, dose intensification may be possible by combining them. The aim of the present study was to determine the maximum tolerated dose of carboplatin combined with fixed doses of cisplatin and cyclophosphamide without and with support of lenograstim. Cisplatin (60 mg/m(2)), cyclophosphamide (600 mg/m(2)) and carboplatin (starting dose 200 mg/m(2)) were given on day 1 every 3 weeks for 4 cycles. Escalated dose levels for carboplatin were planned by increments of 50 mg/m(2) per level. Lenograstim (L) (150 mu g/m(2)/day subcutaneously) was given in case of grade 4 leukopenia (levels without support) or from day 5 up to leukocyte >10,000/mm(3) after nadir (levels with support). Four levels were studied (200, 250, 250 + lenograstim, 300 + lenograstim) with 7, 7, 8, and 7 patients enrolled, respectively. Unacceptable toxicity was induced in 1 patient at the level I (grade 4 thrombocytopenia), in 4 patients at the level 2 (2 prolonged grade 2 leukopenia, 1 grade 4 leukopenia with concomitant grade 4 thrombocytopenia and 1 grade 4 thrombocytopenia), in 1 patient at the level 2 + L (grade 4 thrombocytopenia) and in 3 patients at the level 3 + L (3 grade 4 thrombocytopenia). Thus, 200 mg/m(2) and 250 mg/m(2) were defined as carboplatin MTDs without and with lenograstim support, respectively. Median total platinum (cisplatin + 1/4 carboplatin) delivered dose-intensities were 33, 32, 38 and 44 mg/m(2)/week at the four levels, respectively. Hematological toxicity was overall mild. In no case was febrile neutropenia recorded. Grade 4 thrombocytopenia was always transient and never symptomatic. Grade 3 vomiting was the only severe non-hematological toxicity reported in 5 patients. Out of 16 patients with measurable disease, 11 objective responses were obtained (5 complete and 6 partial) for an overall response rate of 69% (95% exact CL 41-89%). Recommended dose of carboplatin is 200 mg/m(2) without and 250 mg/m(2) with support of lenograstim when combined with cisplatin 60 mg/m(2) and cyclophosphamide 600 mg/m(2). Dose limiting toxicity is persistent leukopenia without and grade 4 thrombocytopenia with support of lenograstim.
RESUMEN
Paraffin-embedded tissues are used in retrospective studies to evaluate the prognostic significance of DNA-flow cytometry (DNA-FCM) in human breast cancer. Although paraffin-embedded samples yield information on disease-free survival (DFS) and overall survival (GAS) of homogeneously selected patients, the resulting DNA-histograms have a lower resolution of aneuploid subpopulations and higher debris levels than those of fresh tumor samples. The aim of this study was to evaluate, retrospectively, the prognostic value of ploidy and the S-phase fraction (SPF) using 515 samples of paraffin-embedded consecutive primary breast cancer tissue (median follow-up: 75.4 months). Ploidy was detectable in 89% cases (34% diploid and 66% aneuploid) and SPF in 77%. The optimal cut-off for SPF was 6%. High SPF values were significantly correlated with shorter DFS (p=0.028) and OAS (p=0.018); aneuploidy was significantly correlated only with a shorter OAS (p=0.0058). Using the Cox proportional hazards regression model to evaluate the independence of DNA-FCM derived parameters, only high SPF was able to predict both a shorter DFS (p=0.02) and OAS (p=0.002). Furthermore, high SPF values were found correlated to aneuploidy (p<0.00001), tumor necrosis (p<0.015) and high histopathological grade (p<0.03). The data reported confirm that SPF is a valuable single independent prognostic factor in human breast, cancer and strongly support the use of archival tumor specimens to study the prognostic role of DNA-FCM in human cancer.
RESUMEN
The antitumor activity and toxicity profile of a new therapeutic combination was investigated for patients with non-Hodgkin's lymphoma (NHL). The regimen consisted of mitoxantrone (10 mg/m(2)/day by intravenous (i.v.) bolus injection on day 1), etoposide (100 mg by 24 hours continuous i.v. infusion on days 1, 2, 3) and bleomycin (4 mg by i.v. bolus injection on day 1 followed by 24 hours continuous i.v. infusion at 4 mg/m2/day dose on days 1, 2, 3) (MEB). MEB chemotherapy was administered to 22 patients affected by intermediate/high grade or clinically symptomatic low grade NHL who were considered non-elegible for standard cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy. Major responses were achieved in 11/22 (50%) patients with 5 (23%) complete responses. Grade 3-4 neutropenia occurred in 59% of patients. The results of this study demonstrate that MEB chemotherapy possesses good antitumor activity and a manageable toxicity in a prognostically unfavourable subset of lymphoma patients.
RESUMEN
The impact of multicentricity in primary breast cancer on relapse or death after radical or modified radical mastectomy was evaluated in 1336 consecutive patients. Multiple tumor foci were found in 11.7% of breast cancers: in 8.4% multicentricity was infiltrating, while in 3.3% of cases an in situ growth pattern was observed. There was a statistically significant association between multicentric primaries and lobular infiltrating carcinoma, age less than or equal to 50 years, large tumors and metastatic axillary nodes, while no relationship was observed with histological grade. Both 5-year disease-free survival and overall survival were shorter in patients with infiltrating multicentric primary tumors. Multivariate analysis confirmed the prognostic role of infiltrating multicentric tumors after adjusting for nodal status, tumor size, age and adjuvant therapy.
RESUMEN
CA 15-3, TPA and CEA were assayed before surgery in 60 patients with breast cancer. A significant association was found between preoperative CA 15-3 levels and some of the most important prognostic factors in breast cancer, such as lymph node status and tumor size. No similar association was discovered for CEA and TPA. Preoperative CA 15-3 levels were also significantly associated with early recurrences of the disease, thus adding useful information to prognosis especially in N+ patients.