Single-agent gemcitabine is active in previously treated metastatic breast cancer.

BACKGROUND: This phase II study was designed to assess the efficacy and safety of gemcitabine in patients with metastatic breast cancer (MBC) previously treated with an anthracycline- or anthracenedione-containing regimen as first-line therapy for metastatic disease. PATIENTS AND METHODS: Forty-seven patients with MBC were enrolled in five French centers. Patients were eligible if they had received one prior chemotherapy regimen with an anthracycline or anthracenedione for metastatic disease, if they had responded to that prior regimen, and if they had relapsed at least 6 months after the first response. Fifteen patients received more than one prior anthracycline regimen; thus, gemcitabine was third-line therapy for 30% of patients. Gemcitabine 1,200 mg/m(2) was administered as a 30-min intravenous infusion on days 1, 8, and 15 of a 28-day cycle for a maximum of eight cycles after the best response was obtained. RESULTS: Objective responses were seen in 12 of 41 assessable patients (4 complete responses and 8 partial responses), for an objective response rate of 29% (95% confidence interval, 16-46%). The median response duration was 8.1 months (range: 2.5-27.4 months). Serious hematological toxicity was minimal, with grade 4 neutropenia in 2% of the patients (no neutropenic fever), grade 3 neutropenia in 28% of the patients, and grade 3 thrombocytopenia in 6% of the patients. Among the nonhematological toxicities, asthenia was the most common. CONCLUSIONS: Gemcitabine given at this dose and schedule is a well-tolerated treatment with definitive antitumor activity in pretreated MBC patients. This result warrants future exploration of the use of gemcitabine as a single agent and in combination in patients with MBC.

[A phase II multicenter study of gemcitabine in non small cell lung cancers]. / Etude multicentrique de phase II de la gemcitabine dans les cancers bronchiques non à petites cellules (CBNPC).

Gemcitabine is a novel pyrimidine nucleoside whose activity has been demonstrated on solid tumors. We report here the results of a multicentre phase II trial of gemcitabine in chemonaive patients with inoperable non small cell lung cancer (NSCLC). Gemcitabine was given weekly at a dose of 1,250 mg/m2 administered as a 30 min intravenous infusion, for 3 weeks followed by 1 week of rest (1 cycle). All the 161 patients included were evaluable for toxicity and 151 of them were evaluable for efficacy. The majority of patients had a stage IIIb (31.1%) or stage IV (64.6%) disease; 10.6%, 83.2% and 6.2% of patients had a WHO performance status (PS) 0, 1, and 2, respectively. Adenocarcinoma accounted for 52.2% of cases and squamous cell carcinoma for 43.5% of cases. Three complete responses and 30 partial responses gave an objective response (OR) rate of 21.8% (95% confidence interval; 15.5-29.3%). All responses were validated by an independent Oncology Review Board. Median duration of response was 7.6 months. Median time to progression was 4.6 months (3.3 months in non responders and 7.6 months in responders). Median survival was 7.3 months in non responders and 13.4 months in responders (p < 0.001), which gave an overall median survival of 8.9 months (95% CI: 0.1-21.9 months) in the entire study population. An improvement of symptoms and personal state was also observed. Treatment was well tolerated. Neutropenia was the only dose limiting toxicity. WHO grade 3 or 4 neutropenia occurred in 19.6% and 5.7% of patients, respectively. With a 21.8% OR rate, this multicentre study confirms the activity of gemcitabine as a single agent in patients with inoperable NSCLC. Its good tolerance and original mode of action make gemcitabine a drug of choice in the therapeutic strategy of these tumors.

Myeloma cell growth arrest, apoptosis, and interleukin-6 receptor modulation induced by EB1089, a vitamin D3 derivative, alone or in association with dexamethasone.

We have previously shown that malignant plasma cells expressed the specific receptor for 1,25-dihydroxyvitamin D3 and that this derivative could significantly inhibit the proliferation of such malignant cells. More recently, new vitamin D3 derivatives have been generated with extraordinarily potent inhibitory effects on leukemic cell growth in vitro. These new data prompted us to (re)investigate the capacity of such new vitamin D3 derivatives to inhibit myeloma cell growth in comparison with that of dexamethasone, a potent antitumoral agent in multiple myeloma. In the current study, we show that EB1089, a new vitamin D3 derivative, (1) induces G1 growth arrest of human myeloma cells, which is only partially reversed by interleukin-6 (IL-6); (2) induces apoptosis in synergy with dexamethasone, IL-6, leukemia-inhibitory factor, and Oncostatin M, with an agonistic anti-gp130 monoclonal antibody being unable to prevent this apoptosis; (3) downregulates both the gp80 (ie, the alpha chain of the IL-6 receptor [IL-6Ralpha]) expression on malignant plasma cells and the production of soluble IL-6Ralpha, and finally (4) inhibits the deleterious upregulation of gp80 expression induced by dexamethasone while limiting the dexamethasone-induced upregulation of gp130 expression. Considering that these in vitro effects of EB1089 have been observed at doses obtainable in vivo (without hypercalcemic effects), our present data strongly suggest that EB1089 could have a true interest in the treatment of multiple myeloma, especially in association with dexamethasone.

[Serum osteocalcin and diabetes mellitus. A study of 98 patients]. / Osteocalcina sierica e diabete mellito. Studio su 98 pazienti.

The goal of this study was to evaluate in 98 diabetic patients the serum levels of osteocalcin (OC) and their relationship with glycosylated hemoglobin levels and with the duration, calculated in years, of the disease. Patients were divided in 3 groups: 17 IDDM patients, 62 NIDDM patients treated with oral hypoglycaemic agents, and 19 NIDDM patients treated with insulin. Results were compared to 2 different control groups. In IDDM patients OC serum levels were significantly lower if compared either to control group and to NIDDM patients. The 2 groups of NIDDM patients showed significantly higher OC values than controls. No significant relationship resulted between OC levels, the duration of diabetes and the glycosylated hemoglobin values. The results of the study indicate a direct correlation between pancreatic function and osteoblastic activity: insulin lack is associated with reduced OC serum levels.

Increasing prevalence of HTLV-III infection in intravenous drug users in Liguria, Italy.

Anti-HTLV III prevalence has been investigated in serum samples of 638 intravenous drug users collected over May 1981 - March 1985 and stored at -20 degrees C. Separately, in a prospective way, we have studied 68 IV drug abusers (53 Genoese and 15 of Sanremo area) of whom we have collected, at least, one serum specimen for each year, starting with 1981. We have also tested for anti-HTLV III presence serum samples of: 91 subjects of Hospital staff (Infectious Diseases Department and Laboratory workers); 32 workers in Therapeutic Communities for drug users and 24 family contacts of anti-HTLV III positive drug users. And then serum samples of two groups of general population collected for other seroepidemiological investigations in 1982 (256 subjects) and 1984 (538 subjects) were tested. No IV drug user was positive in 1981 whilst from 1982 up to 1984 there was a strong rising of the prevalence of anti-HTLV III positive subjects: 2, 22, and 39 per cent, respectively. The prevalence remained about 40% in the first months of 1985. The investigations carried out also show that HTLV III spread in Sanremo area slightly before than in Genoa and neighbourhood. No subject positive for anti-HTLV III has been detected among the Hospital staff and in workers of Therapeutic communities who have more probability to get in contact with infected subjects or their blood, as well as in the general population. A positive case has been discovered in a family contact (the wife of a positive for anti-HTLV III IV drug user). Some epidemiological and public health questions linked to the situation observed, at present, in Liguria, are discussed.

Prevalence of infections caused by AIDS and hepatitis B viruses in jailed people.

Prevalence of positive subjects to anti-HTLV III and HBV markers (HBsAg; anti-HBc; anti-HBs) has been studied both among jailed people and wardens of Sanremo Jail. Out of 92 subjects in custody, 11 were anti-HTLV III positive and 44 had acquired HBV infection markers (antigen and/or antibodies). One of the wardens resulted anti-HTLV III positive whilst 14 appeared to have been infected by HBV. All anti-HTLV III positive subjects, but the warden, were intravenous drug users. The study of prevalence was the first step of a perspective monitoring program in Ligurian Jails.

Detection of platelet antibodies by flow cytometric analysis.

A rapid, sensitive indirect immunofluorescence assay utilizing flow cytometry to detect immune-mediated thrombocytopenia is described. Fluorescein-conjugated F(ab')2 antihuman IgG or IgGAM is reacted with donor platelets after their incubation with test sera and the resulting immune complex is measured using flow cytometric analysis. With this technique excess of Ig on the platelet, expressed as a ratio of fluorescence of test sera/autologous control sera, was noted in 24 of 30 patients (80%) with immune thrombocytopenias caused by auto- or allo-antiplatelet antibodies. Twenty-four sera from nonimmune thrombocytopenic patients were consistently negative. This technique has the advantage of being highly reproducible and avoids the subjective interpretation inherent with manual immunofluorescence assays.

Are lymphocyte subset determinations affected by storage conditions?

The effect of overnight storage, either at room temperature or at 4 degrees C, on total T cells, helper cells, suppressor cells, and HLA-DR-positive cells was determined by flow cytometry and fluoresceinated monoclonal antibodies on peripheral whole blood samples. No differences were noted in any of the subsets regardless of storage conditions when samples were analyzed within 24 hr.

A quantitative immunofluorescence assay for IgM rheumatoid factor.

A quantitative immunofluorescence assay for IgM rheumatoid factor (RF) has been developed using the FIAX fluorometer. Two hundred and six (206) patient serum samples submitted for RF or antinuclear antibody testing were assayed by the fluorometric method and by the sheep cell slide agglutination test (Rheumaton, Wampole Laboratories) currently used in our clinical laboratory. There was an overall agreement of 95.1% between the 2 methods. The fluorometric RF assay is simple, sensitive, reproducible, and does not suffer from the subjectivity present in slide agglutination tests.