RESUMO
BACKGROUND: The Brown University Oncology Research Group performed a phase I study to remove irinotecan from FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan, and leucovorin) and substitute nab-paclitaxel. METHODS: Patients with newly diagnosed advanced pancreatic adenocarcinoma were eligible. Patients received oxaliplatin 85 mg/m, leucovorin 400 mg/m, and 5-fluorouracil 2400 mg/m with 3 dose levels of nab-paclitaxel (125, 150, and 175 mg/m) every 2 weeks. Dose-limiting toxicities were assessed in the first 2 cycles of treatment. The final dose level was expanded to assess cumulative neurotoxicity. RESULTS: Thirty-five patients were entered; 24 with metastatic and 11 with locally advanced pancreatic cancer. The maximum tolerated dose of nab-paclitaxel was 150 mg/m every 2 weeks with FOLFOX. Cumulative neuropathy was the most important toxicity. Grade 3 neuropathy developed in 2 of the first 6 patients at 10 and 11 cycles of FOLFOX-A. Following an amendment to reduce oxaliplatin to 65 mg/m if grade 2 neuropathy developed, no additional patients developed grade 3 neurotoxicity. Twenty-one of 35 patients (60%) had a partial response. The median survival for patients with metastatic disease was 15 months. CONCLUSIONS: The maximum tolerated dose of nab-paclitaxel is 150 mg/m every 2 weeks with FOLFOX. The regimen of FOLFOX-A represents a promising treatment for pancreatic cancer.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Adenocarcinoma/mortalidade , Adulto , Idoso , Albuminas/administração & dosagem , Albuminas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Infusões Intravenosas , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Dose Máxima Tolerável , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Neoplasias Pancreáticas/mortalidade , Prognóstico , Estudos Prospectivos , Medição de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
In the last decade, the advent of biological targeted therapies has revolutionized the management of several types of cancer, especially in the realm of hematologic malignancies. One of these pathways, and the center of this review, is the phosphatidylinositol-3-kinase (PI3K) pathway. The PI3K pathway seems to play an important role in the pathogenesis and survival advantage in hematologic malignancies, such as leukemia, lymphoma, and myeloma. The objectives of the present review, hence, are to describe the current knowledge on the PI3K pathway and its isoforms, and to summarize preclinical and clinical studies using PI3K inhibitors, focusing on the advances made in hematologic malignancies.
