Activity and safety of bevacizumab plus fotemustine for recurrent malignant gliomas.

BACKGROUND: No established chemotherapeutic regimen exists for the treatment of recurrent malignant gliomas (rMGs). Herein, we report the activity and safety results of the bevacizumab (B) plus fotemustine (FTM) combination for the treatment of rMGs. PATIENTS AND METHODS: An induction phase consisted of B 10 mg/kg days 1, 15 plus FTM 65 mg/m(2) days 1, 8, and 15. Nonprogressive patients entered the maintenance phase with B 10 mg/kg plus FTM 75 mg/m(2) every 3 weeks. The primary endpoint was response rate; secondary endpoints included safety, progression free survival (PFS), and overall survival (OS). RESULTS: Twenty-six patients affected by recurrent MGs (50% glioblastoma) were enrolled. Eight partial responses (31%) were observed. Median PFS and OS were 4 (95% C.I.: 2.8-5.1) and 6 months (95% C.I.: 4.2-7.8), respectively. Responses were significantly associated with both improved PFS and OS (P = 0.002 and P = 0.001, resp.). Treatment adverse events were mostly mild to moderate in intensity. Bevacizumab-related adverse events included grade 3 venous thromboembolic event (8%), grade 2 epistaxis (4%), hypertension (8%), and gastrointestinal perforation (4%). CONCLUSIONS: Bevacizumab plus FTM showed activity and good tolerability in pretreated MGs. Further investigations are needed in order to verify the benefits deriving from the addition of B to a cytotoxic in this clinical setting of patients.

Lacosamide as add-on in brain tumor-related epilepsy: preliminary report on efficacy and tolerability.

Lacosamide (LCM) is an antiepileptic drug (AED) that has demonstrated a good efficacy in controlling seizures as an add-on in adult epilepsy. To date, there have been no studies on LCM in patients with brain tumor-related epilepsy (BTRE). To evaluate efficacy and tolerability of LCM as an add-on in BTRE, we followed 14 patients suffering from BTRE who had already been treated with other AEDs and who had not experienced adequate seizure control. Eleven patients underwent chemotherapy while being treated with LCM. Mean duration of follow up was 5.4 months (min < 1 max 10 months). Mean seizure number in the last month prior to the introduction of LCM had been 15.4. At last follow-up, the mean seizure number was reduced to 1.9/month. Lacosamide mean dosage was of 332.1 mg/day (min 100 max 400 mg/day). Responder rate was 78.6%. One patient discontinued LCM because of side-effects. There were no other reported side-effects. Preliminary data on the use of LCM in add-on in patients with BTRE indicate that this drug may represent a valid alternative as an add-on in this particular patient population. However, larger samples are necessary in order to draw definitive conclusions.

Efficacy and tolerability of zonisamide as add-on in brain tumor-related epilepsy: preliminary report.

BACKGROUND: Zonisamide (ZNS) is an antiepileptic drug (AED) with broad spectrum action that demonstrated a good efficacy in controlling seizures as add-on in adult and pediatric epilepsy. To date there have been no studies on ZNS in patients with brain tumor-related epilepsy (BTRE). AIM OF THE STUDY: To evaluate efficacy and tolerability of ZNS as add-on in BTRE. METHODS: We followed six patients suffering from BTRE who had already been treated with other AEDs and who had had not experienced adequate seizure control. Three patients underwent chemotherapy while being treated with ZNS. Mean duration of follow-up was 8 months. RESULTS: Mean seizure number in the last month prior to the introduction of ZNS had been 27.7/month. ZNS mean dosage was of 283.3 mg/day. At last follow-up, the mean seizure number was reduced to 8.8/month. Responder rate was 83.3%.Two patients discontinued the drug because of side effects. There were no other reported side effects. CONCLUSIONS: Preliminary data on the use of ZNS in add-on in patients with BTRE indicate that this drug may represent a valid alternative as add-on in this particular patient population. However, larger samples are necessary to draw definitive conclusions.

Outcome and tolerability of topiramate in brain tumor associated epilepsy.

Epilepsy in brain tumor patients is often refractory to pharmacological treatments and can complicate the therapeutic management of these patients. We conducted a prospective, observational study. The aim of this study was to investigate the efficacy and tolerability of topiramate (TPM) in brain tumor associated epilepsy. We studied 47 patients with brain tumors and epilepsy. The entire group was administered AEDs. TPM was the first therapeutic choice in 14 patients, while in the remaining 33 patients previous AEDs were modified and TPM was introduced due to side effects or inefficacy of the first drug. Follow-up ranged from 3 to 48 months (mean 16.5 months). Considering the final follow-up of each patient who assumed TPM for at least 3 months, we observed 45 patients: 25 were seizure free (55.6%), 9 had a reduction of seizure frequency (SF) higher than 50% (20%) and 11 were stable (24.4%). TPM responder rate was 75.6%. Three patients (6.4%) discontinued TPM for severe side effects (1 after 4 months and 2 after 1 month) and 4 (8.5%) had mild and reversible side effects. In the group of patients who had been in therapy with other AEDs prior to entering the study (n = 33), 19 patients had side effects (57.6%). During follow-up, the haematological parameters were in the normative ranges. Tumor-related seizures are difficult to control with AEDs; the precise reasons for this difficulty are not yet clear. Using TPM, we obtained good seizure control with a low incidence of side effects.

Home rehabilitation for brain tumor patients.

UNLABELLED: To determine whether a program of post-discharge rehabilitation at home for patients operated for brain tumor was associated with functional gain and improvement in Quality of Life (QoL). One hundred and twenty-one patients affected by malignant brain tumor were enrolled in a program of post-discharge home care including neurorehabilitation. Functional outcome was evaluated with Barthel Index (BI) and Karnofsky Performance Status (KPS) measured before and after rehabilitation. The impact of rehabilitation on quality of life was evaluated with a quality of life questionnaire (EORTC QLQ-C30-BM 20). RESULTS: Barthel Index improved in 47 (39%) patients, was stable in 20 (16%) and worsened in 54 (44%). Only 54 patients completed the QoL questionnaire before and after treatment. After three months of rehabilitation, 72% of patients were found to have an improvement in at least one domain score compared with their baseline QoL scores. Rehabilitation at home in brain tumor patients was associated with significant functional gain measured both with BI and KPS. The benefit of rehabilitation may influence patient's perception of quality of life.

Measurement of branching fractions and mass spectra of B-->Kpipigamma.

We present a measurement of the partial branching fractions and mass spectra of the exclusive radiative penguin processes B-->Kpipigamma in the range m(Kpipi)<1.8 GeV/c(2). We reconstruct four final states: K(+)pi(-)pi(+)gamma, K(+)pi(-)pi(0)gamma, K(S)(0)pi(-)pi(+)gamma, and K(S)(0)pi(+)pi(0)gamma, where K(S)(0)-->pi(+)pi(-). Using 232 x 10(6) e(+)e(-)-->BB events recorded by the BABAR experiment at the SLAC PEP-II asymmetric-energy storage ring, we measure the branching fractions B(B(+)-->K(+)pi(-)pi(+)gamma)=[2.95+/-0.13(stat)+/-0.20(syst)] x 10(-5), B(B(0)-->K(+)pi(-)pi(0)gamma)=[4.07+/-0.22(stat)+/-0.31(syst)] x 10(-5), B(B(0)-->K(0)pi(+)pi(-)gamma)=[1.85+/-0.21(stat)+/-0.12(syst)] x 10(-5), and B(B(+)-->K(0)pi(+)pi(0)gamma)=[4.56+/-0.42(stat)+/-0.31(syst)] x 10(-5).

Early post-operative MRI: correlation with progression-free survival and overall survival time in malignant gliomas.

Forty-seven patients with Glioblastoma (42) and Anaplastic Astrocytoma (5) were studied with MR 24 hrs after surgery. In order to evaluate the role of early MR in defining the extent of surgical resection and its relation with the prognosis of malignant glioma patients, three categories of surgical resection were considered: gross total, sub-total and partial resection. The results were correlated with progression-free survival (PFS) and overall survival (ST). As demonstrated by early-MR, gross total resection was performed in 17 patients, sub-total and partial resection in 19 and 11 patients, respectively. The PFS was 6 months in gross total resection, 6 and 3 months in sub-total and in partial resection, respectively. The median survival time was 16 months in total resection patients, 13 months and 7 months in sub-total resection and partial resection patients, respectively. The study confirms that early-MR has to be considered an accurate technique for monitoring the extension of malignant glioma surgical resection and shows a good correlation between early-MR findings, PFS and ST.

Search for the rare decay B0-->tau+tau- at BABAR.

We present the results of a search for the decay B0-->tau+tau- in a data sample of (232+/-3)x10(6) Upsilon(4S)-->BB decays using the BABAR detector. Certain extensions of the standard model predict measurable levels of this otherwise rare decay. We reconstruct fully one neutral B meson and seek evidence for the signal decay in the rest of the event. We find no evidence for signal events and obtain Beta(B0->tau+tau-)<4.1x10(-3) at the 90% confidence level.

Determinations of from inclusive semileptonic decays with reduced model dependence.

We report two novel determinations of /|Vub/ with reduced model dependence, based on measurements of the mass distribution of the hadronic system in semileptonic B decays. Events are selected by fully reconstructing the decay of one B meson and identifying a charged lepton from the decay of the other B meson from Upsilon(4S)-->BB events. In one approach, we combine the inclusive B-->Xulambdav rate, integrated up to a maximum hadronic mass mX<1.67 GeV/c2, with a measurement of the inclusive B-->Xsgamma photon energy spectrum. We obtain /Vub/=(4.43+/-0.38stat+/-0.25syst+/-0.29theo) x 10-3. In another approach we measure the total B-->Xulambdav rate over the full phase space and find /Vub/=(3.84+/-0.70stat+/-0.30syst+/-0.10theo) x 10-3.

Measurement of branching fractions and resonance contributions for B0 --> D0K+pi- and search for B0 --> D0K+pi- decays.

Using 226 x 10(6) gamma(4S) --> BB events collected with the BABAR detector at the PEP-II e+e- storage ring at the Stanford Linear Accelerator Center, we measure the branching fraction for B0 --> D0K+pi-, excluding B0 --> D*-K+, to be beta(B0 --> D0K+pi-) = (88 +/- 15 +/- 9) x 10(-6). We observe B0 --> D0K*(892)0 and B0 --> D2*(2460)-K+ contributions. The ratio of branching fractions beta(B0 --> D*-K+)/beta(B0 --> D*-pi+) = (7.76 +/- 0.34+/-0.29)% is measured separately. The branching fraction for the suppressed mode B0 --> D0K+pi- is beta(B0 --> D0K+pi-) < 19 x 10(-6) at the 90% confidence level.

Search for lepton flavor violation in the decay tau+/--->e+/-gamma.

A search for the nonconservation of lepton flavor in the decay tau+/--->e+/-gamma has been performed with 2.07x10(8) e+e--->tau+tau- events collected by the BABAR detector at the SLAC PEP II storage ring at a center-of-mass energy near 10.58 GeV. We find no evidence for a signal and set an upper limit on the branching ratio of Beta(tau+/--->e+/-gamma)<1.1x10(-7) at 90% confidence level.

Measurements of the absolute branching fractions of B+/- --> K+/-X(cc).

We study the two-body decays of B+/- mesons to K+/- and a charmonium state X(cc) in a sample of 210.5 fb(-1) of data from the BABAR experiment. We perform measurements of absolute branching fractions beta(B+/- --> K+/-X(cc)) using a missing mass technique, and report several new or improved results. In particular, the upper limit beta(B+/- --> K+/- X(3872)) < 3.2 x 10(-4) at 90% C.L. and the inferred lower limit beta(X(3872)J/psipi+ pi-) > 4.2% will help in understanding the nature of the recently discovered X(3872).

Measurements of branching fractions and Dalitz distributions for B0 --> D(*)+/-K0pi-/+ decays.

We present measurements of the branching fractions for the three-body decays B0 --> D(*)-/+K0pi+/- and their resonant submodes B0 --> D(*)-/+K*+/-using a sample of approximately 88 x 10(6) BB pairs collected by the BABAR detector at the SLAC PEP-II asymmetric energy storage ring. We measure: B(B0 --> D-/+K0pi+/-) = (4.9 +/- 0.7stat +/- 0.5syst) x 10(-4), B(B0 --> D*-/+K0pi+/-) = (3.0 +/- 0.7stat +/- 0.3syst) x 10(-4), B(B0 --> D-/+K*+/-) = (4.6 +/- 0.6stat +/- 0.5syst) x 10(-4), B(B0 --> D*-/+K*+/-) = (3.2 +/- 0.6stat +/- 0.3syst) x 10(-4). From these measurements we determine the fractions of resonant events to be f(B0 --> D-/+K*+/-) = 0.63 +/- 0.08stat +/- 0.04syst and f(B0 --> D*-/+K*+/-) = 0.72 +/- 0.14stat +/-0.05syst.

Search for lepton-flavor and lepton-number violation in the decay tau(-) -->l-(+)h+(-)h'(-).

A search for lepton-flavor and lepton-number violation in the decay of the tau lepton into one charged lepton and two charged hadrons is performed using 221.4 fb(-1) of data collected at an e+e- center-of-mass energy of 10.58 GeV with the BABAR detector at the SLAC PEP-II storage ring. In all 14 decay modes considered, the observed data are compatible with background expectations, and upper limits are set in the range B(tau-->lhh')<(0.7 - 4.8) x 10(-7) at 90% confidence level.

Evidence for B+ --> K0K+ and B0 --> K0K0, and measurement of the branching fraction and search for direct CP violation in B+ --> K0pi+.

We present evidence for the b --> d penguin-dominated decays B+ --> K0K+ and B0 --> K0K0 in 227 x 10(6) Y(4S) --> BB decays collected with the BABAR detector. We measure the branching fractions B(B+ --> K0K+) = (1.5 +/- 0.5 +/- 0.1) x 10(-6)(< 2.4 x 10(-6)) and B(B0 --> K0K0) = [formula: see text], where the uncertainties are statistical and systematic, respectively. We also present improved measurements of the charge-averaged branching fraction B(B+ --> K0pi+) = (26.0 +/- 1.3 +/- 1.0) x 10(-6) and CP-violating charge asymmetry A(CP) (K0pi+) = -0.09 +/- 0.05 +/- 0.01), where the uncertainties are statistical and systematic, respectively.

Determination of |Vub| from measurements of the electron and neutrino momenta in inclusive semileptonic B decays.

We present a determination of the Cabibbo-Kobayashi-Maskawa matrix element |Vub| based on the analysis of semileptonic B decays from a sample of 88 x 10(6) Gamma(4S) decays collected with the BABAR detector at the SLAC PEP-II e+e- storage ring. Charmless semileptonic B decays are selected using measurements of the electron energy and the invariant mass squared of the electron-neutrino pair. We obtain |Vub| =(3.95 +/- 0.26(+0.58)(-0.42) +/- 0.25) x 10(-3), where the errors represent experimental uncertainties, heavy quark parameter uncertainties, and theoretical uncertainties, respectively.

Measurement of the Cabibbo-Kobayashi-Maskawa angle gamma in B+/--->D*K+/- decays with a Dalitz analysis of D-->K0(S)pi-pi+.

We report on a measurement of the Cabibbo-Kobayashi-Maskawa CP-violating phase gamma through a Dalitz analysis of neutral D decays to K0(S)pi-pi+ in the processes B+/- -->D*K+/-, D*-->Dpi0, Dgamma. Using a sample of 227 x 10(6) BB pairs collected by the BABAR detector, we measure the amplitude ratios r(B)=0.12+/-0.03+/-0.04 and r*(B)=0.17+/-0.10+/-0.03+/-0.03, the relative strong phases delta(B)=(104+/-45(+17+16)(-21-24))degrees and delta*(B)=(-64+/-41(+14)(-12)+/-15) degrees between the amplitudes A(B- -->D*0K-) and A(B- -->D*0)K-), and gamma=(70+/-31(+12+14)(-10-11))degrees. The first error is statistical, the second is the experimental systematic uncertainty, and the third reflects the Dalitz model uncertainty. The results for the strong and weak phases have a twofold ambiguity.

Measurement of time-dependent CP asymmetries in B0-->D(*)+/-D+/- decays.

We present a first measurement of CP asymmetries in neutral B decays to D+D-, and updated CP asymmetry measurements in decays to D(*+)D- and D(*-)D+. We use fully reconstructed decays collected in a data sample of (232+/-3) x 10(6) gamma(4S)-->BB events in the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. We determine the time-dependent asymmetry parameters to be SD(*+)(D-)=-0.54+/-0.35+/-0.07, CD(*+)(D-)=0.09+/-0.25+/-0.06, SD(*-)(D+)=-0.29+/-0.33+/-0.07, CD(*-)(D+)=0.17+/-0.24+/-0.04, SD+(D-)=-0.29+/-0.63+/-0.06, and CD+(D-)=0.11+/-0.35+/-0.06, where in each case the first error is statistical and the second error is systematic.

Measurement of branching fractions and charge asymmetries in B+ decays to eta pi+, eta K+, eta rho+, and eta' pi+, and search for B0 decays to eta K0 and eta omega.

We present measurements of branching fractions and charge asymmetries for six B-meson decay modes with an eta or eta(') meson in the final state. The data sample corresponds to 232 x 10(6) BB pairs collected with the BABAR detector at the PEP-II asymmetric-energy e(+)e(-) B Factory at SLAC. We measure the branching fractions (in units of 10(-6)): B(B+ -->eta pi(+))=5.1+/-0.6+/-0.3, B(B+ etaK+)=3.3+/-0.6+/-0.3, B(B0-->etaK0)=1.5+/-0.7+/-0.1 (<2.5 at 90% C.L.), B(B+-->eta rho(+))=8.4+/-1.9+/-1.1, B(B0-->eta omiga)=1.0+/-0.5+/-0.2 (<1.9 at 90% C.L.), and B(B+-->eta(')pi(+))=4.0+/-0.8+/-0.4, where the first uncertainty is statistical and second systematic. For the charged modes we also determine the charge asymmetries, all found to be compatible with zero.