Epidoxorubicin plus ifosfamide in advanced and/or metastatic soft-tissue sarcomas.

We undertook this phase II study to evaluate the efficacy and toxicity of epidoxorubicin and ifosfamide in the treatment of locally advanced and/or metastatic soft-tissue sarcomas. We used escalating doses of epidoxorubicin (from 60 to 75 mg/m2) on day 1 and 1.2 g/m2 ifosfamide on days 1-5. Chemotherapy courses were repeated every 3-4 weeks. A total of 16 patients--13 who had not previously been treated and 3 who had undergone prior therapy with anthracyclines--entered the study. In all, 15 patients were evaluable for response and 16, for toxicity. At least two courses of chemotherapy were given. A complete remission (CR) was seen in 1 patient, a partial remission (PR) in 5, and a minor response (MR) in 1, for an objective response rate (CR + PR) of 40% (6/15); this value reached 50% in non-pretreated patients (6/12). Stable disease (SD) was observed in 40% (6/15) of patients. The relative dose intensity of epidoxorubicin ranged from 10 to 23.3 mg/m2 (median, 16.6 mg/m2). The time to objective response ranged from 4 to 12 weeks (median, 8.5 weeks). The duration of response was 4 months for the single CR, and that for the five PRs was 6+ months (range, 4-18 months). Toxicity was evaluated according to WHO criteria in 16 patients; it was mild and consisted mainly of alopecia, nausea and vomiting, and leucopenia. In only three patients did we observe grade 3 leucopenia. In one case an ifosfamide-associated encephalopathy occurred, but it regressed after 24 h. Neither chronic nor acute cardiac toxicity was reported. In this preliminary analysis, the response rate obtained with the combination of epidoxorubicin and ifosfamide was encouraging and the toxicity was acceptable.

Different techniques for drug cytotoxicity evaluation on MCF-7 human breast cancer cell line.

Contrasting results have been reported following the use of different in vitro techniques for the evaluation of drug cytotoxicity on cultured cell lines. Our interest focuses on the evaluation of drug cytotoxicity on a ER+ breast cancer cell line (MCF-7). The present study compares the effect of Doxorubicin using the following different techniques: a dye exclusion test; cell growth after treatment, expressed either as slope of cell growth curves or as the number of cells in treated cultures as a percentage of the number of cells in control cultures at different time intervals after treatment; a clonogenic assay in liquid medium. The dye exclusion assay failed to demonstrate drug-related killing of cells. Our data from the present study support the relative superiority of clonogenic assay compared to other methods. However, the occasional use of different methods could by-pass the limitations of this assay, and, depending on the specific experimental conditions, could lead to a better definition of drug cell killing.

A multifactorial analysis of different biological and clinical parameters in breast cancer.

Different biological and clinical parameters were correlated in a consecutive series of breast cancer patients. Age, tumor size, hormonal receptor status, grading and lymph nodal status (N) were taken into account. A linear logistic regression analysis was performed for 83 patients in whom all parameters were known. Lymph nodal involvement was observed more frequently in tumors with a diameter larger than 2 cm (RR = 3.83; p less than 0.05); it was also more frequently observed in undifferentiated tumors (G2-3), although these data were not significant (RR = 2.75). Neither age nor hormonal receptors were related to lymph nodal involvement. A significant relationship between age and estrogen receptors (ER) was found: younger women had a greater frequency of ER negative tumors (RR = 8.81; p less than 0.005). An opposite tendency was found as regards progesterone receptor status (PgR) (RR = 0.20; p less than 0.05), although these data require further confirmation. No obvious correlation was found between tumor size and hormonal receptor content, although in younger patients tumor size seems to influence ER levels: tumors larger than 2 cm were 1.43 times more often ER negative than tumors smaller than 2 cm. There was no correlation between ER and grading, although G3 tumors were found to be ER negative more frequently than others (RR = 1.71; ns) and showed a tendency to be PgR negative (RR greater than 3). Finally, tumors with lower ER levels were more frequently PgR negative (RR = 11.89; p less than 0.001).

Effect of 17-beta-estradiol on doxorubicin cytotoxicity in human breast cancer cell culture.

Pre-treatment with 17-beta-estradiol appeared to improve the cytotoxic efficacy of doxorubicin on MCF-7 but not on ZR-75-1 and EVSA-T human breast cancer cell lines. MCF-7 and ZR-75-1 are both estrogen receptor-positive cell lines: however, only ZR-75-1 showed improved proliferation in the presence of estradiol. On the other hand MCF-7 appeared basically more resistant to doxorubicin compared to the other cell lines. The results indicate that estrogenic pre-treatment is a potential tool for partially overcoming human breast cell resistance to doxorubicin; moreover, they suggest that the mechanism of interaction could be not exclusively related to actual cytokinetics modulation.

Chemotherapy-induced amenorrhea and other clinical and pathological parameters in the prognosis of breast cancer patients.

147 stage II pre- and perimenopausal breast cancer patients were treated with cyclophosphamide-methotrexate-5-fluorouracil (CMF)- based adjuvant regimens. 103 (72%) patients became amenorrheic during or immediately after the end of the chemotherapy program. Univariate analyses for age, menstrual status, nodal involvement, grading, estrogen and progesterone receptor status indicated no correlation between induction of amenorrhea and a significant prolongation of overall and disease-free survival. Multivariate analyses confirmed that young age at diagnosis, increasing number of infiltrated nodes, negative progesterone receptor status and grade 3 tumors are associated with a worse prognosis. Our results suggest that no benefit is expected in women with drug induced amenorrhea after CMF adjuvant treatment.

[Primary pneumococcal peritonitis: description of a case and review of the literature]. / La peritonite primitiva da pneumococco: descrizione di un caso e revisione della letteratura.

Streptococcus pneumoniae causes lobar pneumonitis but primary peritonitis can occur in cyrrotic adults as well as in children affected by nephrosis and immunopathies. In young females peritonitis can be the consequence of infection localized at genital organs. Pneumococcal sepsis is becoming rare with the antibiotic era but resistance to penicillin is actually frequent and is becoming a problem for elderly. We report a case of a young woman affected by spontaneous primary peritonitis and pneumococcal sepsis. The prevalent symptoms were gastrointestinal: diarrhea and emesis. No infectious foci could be detected on imaging studies and during surgery.

[Familial Mediterranean fever: report of a case]. / La febbre mediterranea familiare: descrizione di un caso.

Familial Mediterranean fever is an autosomal recessive hereditary disease characterised by recurrent fever, poliserositis, chest and/or abdominal pain. Up to date diagnosis is based on clinical symptoms, familial anamnesis and response to colchicine. It is an inflammatory reaction affecting serosal tissues but until recently different hypotheses have been suggested to explain the greatly increased chemotactic activity of the polymorfonuclear leucocytes. Identification of the function of the MEFV gene on chromosome 16 and its protein allows us to understand the pathogenesis of familial Mediterranean fever as well as provides a new diagnostic test and therapeutic measures. We describe a case of an young patient and review the literature.

[Biological aspects and perspectives applicable to the chemoprevention of cancer of the upper respiratory-digestive tract]. / Aspetti biologici e prospettive applicative della chemioprevenzione nel cancro delle vie aero-digestive superiori.

After defining chemoprevention a description is given of the phases of differentiation in normal epithelial cells and the features of proliferation in neoplasias developing in this epithelium. The latest studies on carcinogenesis indicate various types of prevention with which one can alter this transformation process. Epidemiological studies have shown that subjects with low serum levels of Vit-A or Beta carotenoids are at high risk of developing epithelial cancer. Three main categories of agents inducing cell transformation are described: a) physiological induction agents; b) non physiological induction agents; c) cytotoxic drugs. In regard to clinical use, some studies have focussed on the importance of Vit-A in chemoprevention of risk conditions (pre-cancerous lesions) and in prevention of cancer recurrence. The authors point out the increasing interest in the use of retinoids in the chemoprevention of head and neck cancer and report some personal clinical experience.

Selenium therapy in patients with precancerous and malignant oral cavity lesions: preliminary results.

Baseline selenium (Se) levels in serum samples were collected from 22 patients with precancerous and 19 with malignant oral cavity lesions as well as from 13 healthy controls of the same geographic areas. Mean serum Se levels were 105, 101, and 77.03 ng/ml in the precancerous, controls, and malignancy groups, respectively. A statistically significant difference (p less than 0.005) was found between the neoplastic and both the precancerous and control groups. After careful clinical evaluation, precancerous patients received three 4-week cycles of Se, in either inorganic or organic form. Of the 22 precancerous patients entering the study, 18 were available for evaluation of clinical response. The analysis of serum Se variations revealed that serum Se levels tended to increase after the first and second cycles and then gradually returned to baseline values. At the end of the therapy, there were two complete responses (CR), five partial responses (PR), six minor responses (MR), and five stable diseases (SD) with an objective response (CR + PR) of 38.8%. Progression after suspension of therapy occurred in 7 of 18 patients; this may indicate the need of a longer treatment period with this essential trace element.