RESUMO
INTRODUCTION: Preoperative radiotherapy followed by total mesorectal excision with adjuvant chemotherapy has been recommended as the preferred treatment method for locally advanced rectal cancer (LARC). Similar rates of local control, survival and toxicity were observed in preoperative long-course chemoradiotherapy (LCRT) (45-50.4 Gy in 25-28 fractions) and in short-course radiotherapy (SCRT) with 25 Gy over five fractions. Both regimens lower the local recurrence rates compared with that of surgery followed by postoperative radiotherapy. With the simplicity and lower cost of SCRT, a growing number of patients have been receiving SCRT as preoperative radiotherapy. However, the currently established SCRT (25 Gy over five fractions) followed immediately by surgery resulted in poor downstaging and sphincter preservation rate. The pathological complete response (pCR) rate is also markedly lower with SCRT than with LCRT (0.7%vs16%). Several studies recommended SCRT with delayed surgery for more than 4 weeks with expectation of improved pathological outcomes and fewer postoperative complications. While a number of clinical trials demonstrated a persistently better overall local control with SCRT than with LCRT, overall survival advantage has not been observed. Since survival is mainly depended on distant metastases, efforts should be made towards more effective pathological response and systemic treatment. Given the apparent advantages of SCRT, we aimed to establish a dose escalation of SCRT and sequential modified FOLFOX6 (mFOLFOX6) as preoperative therapy for LARC with objectives of achieving an optimal balance of safety, cost effectiveness and clinical outcome, and to support further investigation of this regimen in a phase II/III setting. METHODS: In this phase I study, three dose levels (6Gy×5F, 7Gy×5F, 8Gy×5F to gross tumour volume, while keeping the rest of irradiated volume at 5Gy×5) of SCRT followed by four cycles of mFOLFOX6 chemotherapy as neoadjuvant therapy will be tested by using the traditional 3+3 design. The pCR rate, R0 resection rate, sphincter preservation rate and treatment related toxicity will be assessed. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of Fujian Medical University Union Hospital (No. 2017YF020-02) and all participants provided written informed consent. Results from our study will be disseminated in international peer-reviewed journals. All study procedures were developed in order to assure data protection and confidentiality. TRIAL REGISTRATION NUMBER: NCT03466424; Pre-results.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos Fase I como Assunto/métodos , Neoplasias Retais/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Terapia Neoadjuvante , Estudos Observacionais como Assunto/métodos , Compostos Organoplatínicos/administração & dosagem , Avaliação de Resultados da Assistência ao Paciente , Seleção de Pacientes , Cuidados Pré-Operatórios/métodos , Dosagem Radioterapêutica , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/cirurgiaRESUMO
AIMS AND BACKGROUND: Locally advanced rectal adenocarcinoma is typically treated with neoadjuvant chemoradiotherapy and surgery. We assessed the effect of an additional cycle of capecitabine/oxaliplatin chemotherapy before surgery in 57 patients with T3/4, N+/- or T1/2, N+ rectal cancer. MATERIALS AND STUDY DESIGN: Radiotherapy (total dose, 50.4 Gy) was combined with three cycles of chemotherapy (two cycles concomitant with radiotherapy), and each cycle consisted of oxaliplatin (130 mg/m2 on day 1) and capecitabine (825 mg/m2, twice per day from day 1 to day 14) for 21 days. In addition to assessing the safety of this treatment, the primary endpoint was pathological complete response (pCR). The secondary endpoint was the change in primary tumor and node stage from pre-treatment to post-surgery. RESULTS: Eleven patients (19%) experienced complete tumor regression and 23 patients (40%) experienced tumor regression grade 3. Tumor down-staging occurred in 31 patients (54.4%) and down-staging of nodes occurred in 25 patients (43.9%). There was a significant difference in tumor stage between pre-treatment and post-surgery (P <0.001). Patients with less advanced N stages had significantly better recurrence-free survival but similar metastasis-free survival and overall survival. Tumor regression grade was not associated with overall survival, recurrence-free survival or metastasis-free survival. The most common adverse events were pulmonary infection (n = 6, 10.5%) and intestinal obstruction (n = 6, 10.5%): CONCLUSIONS. An additional cycle of chemotherapy given after chemoradiotherapy and before surgery provided good efficacy and had a satisfactory safety profile in patients with locally advanced rectal cancer.
Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Terapia Neoadjuvante/métodos , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Quimioterapia Adjuvante , Ensaios Clínicos Fase II como Assunto , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Projetos Piloto , Radioterapia Adjuvante , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the effects of early rehabilitation on activities of daily living (ADL) and complications in patients within 1 month after a first stroke. METHODS: 57 stroke patients were randomly divided into rehabilitation group (30 cases) and control group (27 cases). Patients in rehabilitation group received rehabilitation intervention (the main methods were therapeutic exercises, especially Bobath method) starting on average (15+/-4) days after stroke. Patients in both groups received the similar pharmological treatments. The demographic information was similar in both groups. Using the degree of deficit of neural function (DDNF,Chinese version), Barthel index and Fugl-Meyer Assessment (FMA) scale to assess all patients in pre-therapy stage and post-therapy stage. RESULTS: The scores of DDNF, FMA and Barthel index except for the grooming item (P=0.04, it is higher in rehabilitation group than in control group) in the 2 groups were similar at the pre-therapy stage (P>0.05). At the post-therapy stage, there was no significant difference in the difference values in the grooming item between the pre- and post-stages in the 2 groups. There were significant differences in the difference values between the pre- and post-stages in the 2 groups in eating, bed-chair transfer and short distance walking activities items put together(P=0.05). The differences between the pre- and post-stages in both groups in Barthel index items except the control of feces and urine, and bath items were significant (P=0.01). The effects on complications were as follows: At the pre-therapy stage, the number of shoulder hand syndrome in rehabilitation group was higher than the one in control group (P=0.11), it was lower in rehabilitation group than in control group (P=0.09) at the post-therapy stage. There were no significant differences about drop foot, interior deviation foot and ankle joint contracture conditions between the 2 groups at the pre-therapy stage, but there were significant differences about the 3 conditions at the post-therapy stage (P=0.01), and the number of 3 complications was lower in rehabilitation group than in control group. There was no significant difference in shoulder subluxation at the pre- and post-therapy stages between the 2 groups. CONCLUSION: Early rehabilitation can effectively improve stroke patients' ADL, especially in eating, bed-chair transfer and short distance walking activities, and decrease the rate of complications' incidence within one month after stroke.