An EORTC-IDBBC phase I study of gemcitabine and continuous infusion 5-fluorouracil in patients with metastatic breast cancer resistant to anthracyclines or pre-treated with both anthracyclines and taxanes.

The aim of this study was to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and potential activity of combined gemcitabine and continuous infusion 5-fluorouracil (5-FU) in metastatic breast cancer (MBC) patients that are resistant to anthracyclines or have been pretreated with both anthracyclines and taxanes. 15 patients with MBC were studied at three European Organization for Research and Treatment of Cancer centres. 13 patients had received both anthracylines and taxanes. Gemcitabine was given intravenously (i.v.) on days 1 and 8, and 5-FU as a continuous i.v. infusion on days 1 through to 14, both drugs given in a 21-day schedule at four different dose levels. Both were given at doses commonly used for the single agents for the last dose level (dose level 4). One of 6 patients at level 4 (gemcitabine 1200 mg/m2 and 5-FU 250 mg/m2/day) had a DLT, a grade 3 stomatitis and skin toxicity. One DLT, a grade 3 transaminase rise and thrombosis, occurred in a patient at level 2 (gemcitabine 1000 mg/m2 and 5-FU 200 mg/m2/day). Thus, the MTD was not reached. One partial response and four disease stabilisations were observed. Only 1 patient withdrew from the treatment due to toxicity. The MTD was not reached in the phase I study. The combination of gemcitabine and 5-FU is well tolerated at doses up to 1200 mg/m2 given on days 1 and 8 and 250 mg/m2/day given on days 1 through to 14, respectively, every 21 days. The clinical benefit rate (responses plus no change of at least 6 months) was 33% with one partial response, suggesting that MBC patients with prior anthracycline and taxane therapy may derive significant benefit from this combination with minimal toxicity.

Long- incubation time- interferon-gamma release assays in response to PPD-, ESAT-6- and/or CFP-10 for the diagnosis of Mycobacterium tuberculosis infection in children.

Background:Diagnosis of childhood active tuberculosis (aTB) or latent Mycobacterium tuberculosis (Mtb) infection (LTBI) remains a challenge, and replacement of tuberculin skin tests (TST) by commercialized interferon-gamma release assays (IGRA) is not currently recommended.Methods:266 children between 1 month and 15 years of age, 214 being at risk of recent Mtb infection and 51 being included as controls, were prospectively enrolled. According results of clinical evaluation, TST, chest X-Ray and microbiology, children were classified as non-infected, LTBI or aTB. Long-incubation time PPD-, ESAT-6-, and CFP-10-IGRA were performed and evaluated for their accuracy to correctly classify the children.Results:Whereas both TST and PPD-IGRA were suboptimal to detect aTB, combining CFP-10-IGRA with TST or with PPD-IGRA allowed us to detect all the children with aTB, with 96% specificity for children who were positive for CFP-10-IGRA. Moreover, combination of CFP-10- and PPD-IGRA also detected 96% of children classified as LTBI, but a strong IFN-γ response to CFP-10 (>500 pg/ml) was highly suggestive of aTB at least among children less than 3 years old.Conclusions:Long-incubation time CFP-10- and PPD-IGRA should help the clinicians to identify quickly aTB or LTBI in young children.

Role of Landau quantization on the neutron-drip transition in magnetar crusts

The role of a strong magnetic field on the neutron-drip transition in the crust of a magnetar is studied. The composition of the crust and the neutron-drip threshold are determined numerically for different magnetic field strengths using the experimental atomic mass measurements from the 2012 Atomic Mass Evaluation complemented with theoretical masses calculated from the Brussels-Montreal Hartree-Fock-Bogoliubov nuclear mass model HFB-24. The equilibrium nucleus at the neutron-drip point is found to be independent of the magnetic field strength. As demonstrated analytically, the neutron-drip density and pressure increase almost linearly with the magnetic field strength in the strongly quantizing regime for which electrons lie in the lowest Landau level. For weaker magnetic fields, the neutron-drip density exhibits typical quantum oscillations. In this case, the neutron-drip density can be either increased by about 14% or decreased by 25% depending on the magnetic field strength. These variations are shown to be almost universal, independently of the nuclear mass model employed. These results may have important implications for the physical interpretation of timing irregularities and quasiperiodic oscillations detected in soft gamma-ray repeaters and anomalous x-ray pulsars, as well as for the cooling of strongly magnetized neutron stars.

Multicenter randomized trial of dacarbazine alone or in combination with two different doses and schedules of interferon alfa-2a in the treatment of advanced melanoma

Purpose: Some phase II studies have suggested that the combination of interferons (IFNs) with dacarbazine (DTIC) in the treatment of malignant melanoma (MM) increases the antitumor activity of DTIC alone. In an attempt to confirm this hypothesis, a randomized study was performed with the further intent of observing whether low doses of recombinant interferon alfa-2a (rIFNα2a) could be as effective as intermediate doses. Patients and Methods: Two hundred sixty-six patients were randomized onto three different treatment arms: DTIC 800 mg/m 2 intravenously (IV) days 1 and 21; DTIC plus rIFNα2a 9 mIU intramuscularly (IM) daily; and DTIC plus rIFNα2a 3 mIU IM three times per week. Major prognostic factors were well balanced among the three arms. Chemotherapy was administered for a maximum of eight cycles. After 6 months of therapy, rIFNα2a was continued until disease progression at 3 mIU three times per week in responding patients who had received the combined treatment. Results: The percentage of objective responses did not differ among the three groups (20%, 28%, and 23%, respectively), although a significant prolongation of response duration was observed when rIFNα2a was added to DTIC (2.6 v 8.4 v 5.5 months, respectively). However, this improvement in response duration did not translate into an amelioration of overall survival. The addition of rIFNα2a led to the onset of flu-like syndrome, but in no case was it necessary to withdraw the treatment program and no toxic deaths or life-threatening toxicities were reported. Conclusion: In this study, rIFNα2a significantly prolonged response duration, whereas no effects on response rate and survival were observed; rIFNα2a 3 mIU appeared to be equally effective and better tolerated than 9 mIU.

Easy preoperative planning of deeply located brain lesions using external skin reference and 3-Dimensional surface MRI

Open skull surgery of deeply located intracerebral lesions requires precise determination of the treatment area in 3-dimensional (3-D) space. 3-D MRI can give important additional information in presurgical determination of the surgical approach to the target, taking into account highly functional brain areas and important vascular structures. The day before surgery, a grid composed of 9 tubings intersecting at 90° at 1 cm intervals and filled with a Q1SO4 solution is firmly attached to the skin of the patient’s head in the presumed region of the craniotomy. A 3-D turbo-FLASH sequence is then performed in the sagittal plane after intravenous Gd-DOTA injection on a IT Magnetom. 3-D surface reconstruction of the cortical gyri and sulci is performed. Once the gyri are identified, the 3-D program is then implemented in order to perform a color display of the cortical veins and of the tumor boundaries. The surgical access is then chosen by the surgeon, taking into account highly functional areas. Finally, the boundaries of the tumor are projected on the cortex reconstruction and on the external reference placed on the skin. The entry place for surgery as well as the size of craniotomy are drawn on the skin and the tubed grid is removed. The accuracy of this method tested in 9 patients with deeply located brain tumors or arteriovenous malformations was very satisfactory. In daily practice, this method is a valuable technique providing important clinical information in determining the shortest and safest way through the brain tissue, decreasing possible functional deficit and reducing craniotomy size in cases of difficult to access deep brain areas. Our method does not require a stereotactic frame permanently fixed to the head of the patient during surgery. © 1994 S. Karger AG, Basel.