RESUMO
CRLX101 is a nanoparticle-drug conjugate with a camptothecin payload. We assessed the toxicity and pathologic complete response (pCR) rate of CRLX101 with standard neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer. A single-arm study was conducted with a 3â¯+â¯3 dose escalation phase Ib followed by phase II at the maximum tolerated dose (MTD). Thirty-two patients were enrolled with 29 (91%) patients having T3/4 and 26 (81%) N1/2 disease. In phase Ib, no patient experienced a dose limiting toxicity (DLT) with every other week dosing, while 1/9 patients experienced a DLT with weekly dosing. The weekly MTD was identified as 15 mg/m2. The most common grade 3-4 toxicity was lymphopenia, with only 1 grade 4 event. pCR was achieved in 6/32 (19%) patients overall and 2/6 (33%) patients at the weekly MTD. CRLX101 at 15 mg/m2 weekly with neoadjuvant CRT is a feasible combination strategy with an excellent toxicity profile. Clinicaltrials.gov registration NCT02010567.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/uso terapêutico , Capecitabina/uso terapêutico , Ciclodextrinas/uso terapêutico , Nanopartículas/química , Terapia Neoadjuvante , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/efeitos adversos , Capecitabina/efeitos adversos , Estudos de Coortes , Ciclodextrinas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Retais/patologiaRESUMO
The incidence of esophageal and gastric malignancies has increased over the last decade. Historically, surgery has been considered the best treatment for these cancers. However, long-term survival after surgery is fair at best, because of the tendency of disease to recur locally and distantly. Presently, the management of these cancers involves surgery, chemotherapy, and radiation therapy. This article discusses various treatment strategies that employ these modalities either alone or in combination, in an attempt to improve survival rates for patients who have gastroesophageal malignancies.