Effectiveness of the bevacizumab-irinotecan regimen in the treatment of recurrent glioblastoma multiforme: Comparison with other second-line treatments without this regimen.

A retrospective cohort study was conducted to analyse the effectiveness of bevacizumab and irinotecan (BVZ/CPT-11) as a second-line treatment in patients with primary glioblastoma multiforme (GBM) in comparison with a control group that were not administered BVZ/CPT-11 at the first recurrence. The difference in overall survival (OS) between the two groups was used as a predictor of effectiveness. OS was calculated according to prognostic factors and gender. A total of 28 and 32 patients were enrolled in the BVZ/CPT-11 cohort and control group, respectively. The median OS was 17.94 months (95% CI, 14.91-20.96) in the BVZ/CPT-11 treatment cohort and 10.97 months (95% CI, 7.65-14.30) in the control cohort. The results obtained on the effectiveness of BVZ/CPT-11 treatment in patients with primary GBM are consistent with data from previous studies. No significant differences were identified in OS based on prognostic factors; therefore, the latter cannot be used to select patients who would incur the greatest benefits from BVZ/CPT-11 treatment.

La notificación on line de reacciones adversas a medicamentos, un avance de la Web del Centro Andaluz de Farmacovigilancia

Boletín semanal para profesionales sanitarios de la Secretaría General de Salud Pública y Participación Social de la Consejería de Salud

Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study

BACKGROUND In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates. METHODOLOGY/PRINCIPAL FINDINGS KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p=0.0038; HR: 1.40; 95% CI:1.12-1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p=0.0002; HR: 1.55; 95% CI: 1.23-1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p=0.0054; OR: 1.77; 95% CI: 1.18-2.64). CONCLUSIONS/SIGNIFICANCE This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.

Plerixafor and granulocyte colony-stimulating factor for first-line steady-state autologous peripheral blood stem cell mobilization in lymphoma and multiple myeloma: results of the prospective PREDICT trial.

In Europe, the combination of plerixafor + granulocyte colony-stimulating factor is approved for the mobilization of hematopoietic stem cells for autologous transplantation in patients with lymphoma and myeloma whose cells mobilize poorly. The purpose of this study was to further assess the safety and efficacy of plerixafor + granulocyte colony-stimulating factor for front-line mobilization in European patients with lymphoma or myeloma. In this multicenter, open label, single-arm study, patients received granulocyte colony-stimulating factor (10 μg/kg/day) subcutaneously for 4 days; on the evening of day 4 they were given plerixafor (0.24 mg/kg) subcutaneously. Patients underwent apheresis on day 5 after a morning dose of granulocyte colony-stimulating factor. The primary study objective was to confirm the safety of mobilization with plerixafor. Secondary objectives included assessment of efficacy (apheresis yield, time to engraftment). The combination of plerixafor + granulocyte colony-stimulating factor was used to mobilize hematopoietic stem cells in 118 patients (90 with myeloma, 25 with non-Hodgkin's lymphoma, 3 with Hodgkin's disease). Treatment-emergent plerixafor-related adverse events were reported in 24 patients. Most adverse events occurred within 1 hour after injection, were grade 1 or 2 in severity and included gastrointestinal disorders or injection-site reactions. The minimum cell yield (≥ 2 × 10(6) CD34(+) cells/kg) was harvested in 98% of patients with myeloma and in 80% of those with non-Hodgkin's lymphoma in a median of one apheresis. The optimum cell dose (≥ 5 × 10(6) CD34(+) cells/kg for non-Hodgkin's lymphoma or ≥ 6 × 10(6) CD34(+) cells/kg for myeloma) was harvested in 89% of myeloma patients and 48% of non-Hodgkin's lymphoma patients. In this prospective, multicenter European study, mobilization with plerixafor + granulocyte colony-stimulating factor allowed the majority of patients with myeloma or non-Hodgkin's lymphoma to undergo transplantation with minimal toxicity, providing further data supporting the safety and efficacy of plerixafor + granulocyte colony-stimulating factor for front-line mobilization of hematopoietic stem cells in patients with non-Hodgkin's lymphoma or myeloma.

First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study.

BACKGROUND Phase-IV, open-label, single-arm study (NCT01203917) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV, epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). METHODS Treatment: gefitinib 250 mg day(-1) until progression. Primary endpoint: objective response rate (ORR). Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objective: EGFR mutation analysis in matched tumour and plasma samples. RESULTS Of 1060 screened patients with NSCLC (859 known mutation status; 118 positive, mutation frequency 14%), 106 with EGFR sensitising mutations were enrolled (female 70.8%; adenocarcinoma 97.2%; never-smoker 64.2%). At data cutoff: ORR 69.8% (95% confidence interval (CI) 60.5-77.7), DCR 90.6% (95% CI 83.5-94.8), median PFS 9.7 months (95% CI 8.5-11.0), median OS 19.2 months (95% CI 17.0-NC; 27% maturity). Most common adverse events (AEs; any grade): rash (44.9%), diarrhoea (30.8%); CTC (Common Toxicity Criteria) grade 3/4 AEs: 15%; SAEs: 19%. Baseline plasma 1 samples were available in 803 patients (784 known mutation status; 82 positive; mutation frequency 10%). Plasma 1 EGFR mutation test sensitivity: 65.7% (95% CI 55.8-74.7). CONCLUSION First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. Plasma samples could be considered for mutation analysis if tumour tissue is unavailable.

Study of the effectiveness of first-line treatment in renal cell carcinoma.

The emergence of novel drugs corresponds with the determination of the effectiveness of the current treatments used in clinical practice. A retrospective observational study was conducted to evaluate the effectiveness of first-line treatments and to test the influence of the prognostic factors established using the Memorial Sloan-Kettering Cancer Center (MSKCC) and the analysis of Mekhail's study for two or more metastatic sites. The primary endpoints were median progression-free survival (mPFS) and median overall survival (mOS) times. A total of 65 patients were enrolled and the mPFS and mOS of the patients treated with sunitinib (n=51) were 9.0 and 20.1 months, respectively, and for the patients treated with temsirolimus (n=14) these were 3.0 and 6.2 months, respectively. In the poor-prognosis (PP) group, a difference of 1.2 months (P=0.049) was found in mPFS depending on the first-line treatment. A difference of 4.1 months (P=0.023) was also found in mPFS when classified by histology (clear verses non-clear cell) in the sunitinib-treatment group. When stratified by the prognostic group, differences of >7 months (P<0.001) were found between the groups. Therefore, it was concluded that the effectiveness of the treatments was reduced compared to previous studies and differences were found in the PP group when classified by first-line drug and histology. Additionally, the influence of prognostic factors on OS and the value of stratifying patients using these factors have been confirmed.

First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study.

BACKGROUND: Phase-IV, open-label, single-arm study (NCT01203917) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV, epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). METHODS: TREATMENT: gefitinib 250 mg day(-1) until progression. Primary endpoint: objective response rate (ORR). Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objective: EGFR mutation analysis in matched tumour and plasma samples. RESULTS: Of 1060 screened patients with NSCLC (859 known mutation status; 118 positive, mutation frequency 14%), 106 with EGFR sensitising mutations were enrolled (female 70.8%; adenocarcinoma 97.2%; never-smoker 64.2%). At data cutoff: ORR 69.8% (95% confidence interval (CI) 60.5-77.7), DCR 90.6% (95% CI 83.5-94.8), median PFS 9.7 months (95% CI 8.5-11.0), median OS 19.2 months (95% CI 17.0-NC; 27% maturity). Most common adverse events (AEs; any grade): rash (44.9%), diarrhoea (30.8%); CTC (Common Toxicity Criteria) grade 3/4 AEs: 15%; SAEs: 19%. Baseline plasma 1 samples were available in 803 patients (784 known mutation status; 82 positive; mutation frequency 10%). Plasma 1 EGFR mutation test sensitivity: 65.7% (95% CI 55.8-74.7). CONCLUSION: First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. Plasma samples could be considered for mutation analysis if tumour tissue is unavailable.