Avaliação de clones de videira "Bordô" para elaboração de sucos tintos.

O trabalho objetivou avaliar seis clones de videira da cv. Bordô, uma das principais uvas comuns cultivadas para processamento no Rio Grande do Sul, devido à tonalidade violácea intensa, ao paladar apreciado pelo consumidor e pela resistência às principais doenças fúngicas. Clones de "Bordô" foram prospectados pela Embrapa Uva e Vinho com o apoio de empresas vitícolas entre 2012 e 2013, considerando: taxa de abortamento floral, estabilidade de produção, tamanhos de cacho e bagas, nos seguintes municípios: Videira (V), Antônio Prado (AP), Garibaldina (GA), Garibaldi (G), Nova Roma do Sul (NRS) e Farroupilha (F)

Pharmacokinetic/pharmacodynamic analysis of adjuvant pegylated interferon α-2b in patients with resected high-risk melanoma

PurposeHigh-dose pegylated interferon α-2b (peginterferon α-2b) significantly decreased disease recurrence in patients with resected stage III melanoma in a clinical study. We investigated the pharmacokinetics (PK) and safety of high-dose peginterferon α-2b in patients with high-risk melanoma.MethodsFor PK analysis, 32 patients received peginterferon α-2b 6 μg/(kg week) subcutaneously for 8 weeks (induction) then 3 μg/(kg week) for 4 weeks (maintenance). PK profiles were determined at weeks 1, 8, and 12. Exposure-response relationships between peginterferon α-2b and absolute neutrophil count (ANC) and alanine aminotransferase (ALT) level were also studied.ResultsPeginterferon α-2b was well-absorbed following SC administration, with a median T (max) of 24 h. Mean half-life estimates ranged from 43 to 51 h. The accumulation factor was 1.69 after induction therapy. PK parameters showed moderate interpatient variability. PK profiles were described by a one-compartmental model with first-order absorption and first-order elimination. Toxicity was profiled and was acceptable; observed side effects were similar to those previously described. Dose reduction produced proportional decreases in exposure and predictable effects on ANC in an Imax model; however, a PK/pharmacodynamic (PK/PD) relationship between peginterferon α-2b and ALT could not be established with high precision.ConclusionsPeginterferon α-2b was well-absorbed and sustained exposure to peginterferon α-2b was achieved with the doses tested. These data confirm and extend previous PK observations of peginterferon α-2b in melanoma and solid tumors. Our PK/PD model of exposure and ANC effect provides useful information for prediction of peginterferon α-2b-related hematologic toxicity

Phase II trial of sagopilone, a novel epothilone analog in metastatic melanoma

BackgroundSagopilone is a novel fully synthetic epothilone with promising preclinical activity and a favourable toxicity profile in phase I testing.MethodsA phase II pharmacokinetic and efficacy trial was conducted in patients with metastatic melanoma. Patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate haematological, and organ function, with up to 2 previous chemotherapy and any previous immunotherapy regimens. Sagopilone, 16 mg m⁻², was administered intravenously over 3 h every 21 days until progression or unacceptable toxicity.ResultsThirty-five patients were treated. Sagopilone showed multi-exponential kinetics with a mean terminal half-life of 64 h and a volume of distribution of 4361 l m⁻² indicating extensive tissue/tubulin binding. Only grade 2 or lower toxicity was observed: these included sensory neuropathy (66%), leukopenia (46%), fatigue (34%), and neutropenia (31%). The objective response rate was 11.4% (one confirmed complete response, two confirmed partial responses, and one unconfirmed partial response). Stable disease for at least 12 weeks was seen in an additional eight patients (clinical benefit rate 36.4%).ConclusionSagopilone was well tolerated with mild haematological toxicity and sensory neuropathy. Unlike other epothilones, it shows activity against melanoma even in pretreated patients. Further clinical testing is warranted

Concurrent 72-hour continuous infusion of etoposide and cisplatin in metastatic breast cancer.

We conducted a multiinstitutional phase II clinical trial to determine the toxicity, response, and survival rate of concurrent 72-h continuous infusion of etoposide and cisplatin in patients with metastatic breast cancer. A total of 26 women were enrolled, 4 of whom received no prior chemotherapy for metastatic disease. All patients were evaluated for toxicity, response, and survival employing the National Cancer Institute (NCI) Common Toxicity Criteria and the Eastern Cooperative Oncology Group (ECOG) response criteria. A total of 84 cycles of therapy were administered, median 3 (range 1 to 6). Severe grade 3 and grade 4 neutropenia occurred in 22 cycles (26%), and there were only 11 episodes (11%) of similar grade thrombocytopenia. Nausea and vomiting were seen in one third of cycles. A single patient (4%) had a complete remission, and seven patients (27%) had partial remissions for an overall objective response rate of 31% (95% confidence interval, 13 to 49%). Three of four patients (75%) without prior therapy for metastatic disease had objective responses. Median survival was 7 months. This combination regimen is active in extensively treated patients with metastatic breast cancer. It is responsible to further investigate the role of etoposide-cisplatin combination chemotherapy as firstline therapy for patients with metastatic breast cancer