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Biomedical subjects

Yu Jo Chua

Publications and source records attributed to Yu Jo Chua.

7 recordsLinked to original sources

Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer.

BACKGROUND: A regimen of epirubicin, cisplatin, and infused fluorouracil (ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma. We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer. METHODS: We randomly assigned patients with resectable adenocarcinoma of the stomach, esophagogastric junction, or lower esophagus to either perioperative chemotherapy and surgery (250 patients) or surgery alone (253 patients). Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin (50 mg per square meter of body-surface area) and cisplatin (60 mg per square meter) on day 1, and a continuous intravenous infusion of fluorouracil (200 mg per square meter per day) for 21 days. The primary end point was overall survival. RESULTS: ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer. Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group (46 percent and 45 percent, respectively), as were the numbers of deaths within 30 days after surgery. The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group. With a median follow-up of four years, 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died. As compared with the surgery group, the perioperative-chemotherapy group had a higher likelihood of overall survival (hazard ratio for death, 0.75; 95 percent confidence interval, 0.60 to 0.93; P=0.009; five-year survival rate, 36 percent vs. 23 percent) and of progression-free survival (hazard ratio for progression, 0.66; 95 percent confidence interval, 0.53 to 0.81; P<0.001). CONCLUSIONS: In patients with operable gastric or lower esophageal adenocarcinomas, a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival. (Current Controlled Trials number, ISRCTN93793971 [controlled-trials.com].).

Adenocarcinoma↗

Chemotherapy for advanced pancreatic cancer.

Single-agent gemcitabine was established as standard treatment for advanced pancreatic cancer after a superior clinical benefit response was demonstrated in a randomized study comparing it to 5-fluorouracil (FU). Until recently, many subsequent randomized trials of newer, often gemcitabine-based combinations have not been able to show improved survival over gemcitabine. Combination gemcitabine and capecitabine is likely to become the preferred standard treatment, at least in the UK, on the basis of the positive interim results of the UK National Cancer Research Institute (NCRI) randomized study of chemotherapy with this combination. At present, there is no standard second-line treatment for patients who have become refractory to gemcitabine, although a recently reported study has suggested that oxaliplatin with FU and leucovorin is superior to best supportive care in these patients. This article will review and discuss the clinical trials of chemotherapy for this disease, including the more recent trials, which have included the novel targeted agents.

Antineoplastic Agents↗

Panitumumab.

Panitumumab, previously known as ABX-EGF, is the first fully human monoclonal antibody to be shown to be effective as a treatment for solid-tumor cancers. Its target is the epidermal growth factor receptor (EGFR), which when overactive may contribute to the development and progression of cancer and is expressed in several solid tumors, including colorectal cancer. In a recently reported phase III trial, patients with metastatic colorectal cancer who had failed previous treatment with oxaliplatin- and irinotecan-based therapy were randomized to receive single-agent panitumumab and best-supportive care, or best-supportive care alone. This trial demonstrated a significant improvement in progression-free survival with panitumumab treatment in these patients. A rash similar to that which occurs with the other anti-EGFR antibody, cetuximab, has been observed in up to 100% of patients treated with panitumumab in the various clinical trials. As with other EGFR antagonists, EGFR staining by immunohistochemistry has not been shown to be an effective method of selecting patients for treatment, whereas the severity of the rash appears to be predictive of outcome. Ongoing randomized trials are evaluating the use of panitumumab with combination treatment for the first-line treatment of metastatic colorectal cancer. This review summarizes the rationale for targeting the EGFR and the development of panitumumab in preclinical and early phase trials in several tumor types. Clinical trial results in colorectal cancer, in which the development of this agent is most advanced, will also be discussed, as will the rash associated with treatment.

Animals↗

Neoadjuvant treatment of unresectable liver metastases from colorectal cancer.

There has been increasing interest in the use of neoadjuvant treatment for downstaging and downsizing disease in patients with initially unresectable liver metastases from colorectal cancer with a view to potentially curative surgery. This has been increasingly feasible with the more active treatment combinations presently available based on oxaliplatin or irinotecan. This article reviews the evidence supporting the use of this treatment strategy and discusses the implications of advances in treatment in other metastatic disease settings for these patients and the issues of patient selection and prognostic factors.

Adenocarcinoma↗

Adjuvant treatment for resectable pancreatic cancer.

There are relatively few randomized studies of adjuvant chemoradiotherapy and chemotherapy in patients with resected pancreatic adenocarcinoma. The European Study Group for Pancreatic Cancer 1 (ESPAC1) trial is the largest study of adjuvant treatment to date. The results of ESPAC1 are discussed in the context of other evidence from previous randomized studies, which have also been combined in a meta-analysis. Overall, the existing data show a clear benefit for postoperative adjuvant chemotherapy, which has not been demonstrated for adjuvant chemoradiotherapy. The subgroup of patients with resection margin positive disease did seem to benefit less from adjuvant chemotherapy, and showed a trend towards improved survival with chemoradiotherapy. Adjuvant chemoradiotherapy should be evaluated further in this latter group of patients. The optimal chemotherapy regimen for use as adjuvant treatment is the subject of ongoing trials. Other strategies which should be explored include neoadjuvant treatment and the incorporation of novel targeted agents into management.

Adenocarcinoma↗

Recent data with anti-epidermal growth factor receptor antibodies and irinotecan in colon cancer.

The epidermal growth factor receptor (EGFR) is overexpressed in the majority of colorectal cancers. It is the target for a class of agents at the forefront of development for the treatment of colorectal cancer, ie, the anti-EGFR monoclonal antibodies, which include cetuximab, panitumumab, and matuzumab. At present, cetuximab is the furthest along in terms of established efficacy in the treatment of metastatic or inoperable disease and is licensed for the treatment of patients with irinotecan-refractory colorectal cancer. This article reviews the recent evidence supporting the combination of these anti-EGFR agents with the cytotoxic chemotherapeutic agent irinotecan.

Antibodies, Monoclonal↗

Recent advances in management of small-cell lung cancer.

Small-cell lung cancer (SCLC) is a smoking-related disease with a poor prognosis. While SCLC is usually initially sensitive to chemotherapy and radiotherapy, responses are rarely long lasting. Frustratingly, most patients ultimately relapse, often with increasingly treatment resistant disease. Many strategies have been developed in an attempt to improve treatment outcomes, which have plateaued since the introduction of combination chemotherapy in the 1980s. These include trials of maintenance therapy, and dose intensification, the latter by means of increasing dose density, growth factor support and high dose chemotherapy with autologous stem cell rescue. None have been shown to improve patient survival. On the other hand, the integration of concurrent thoracic radiation and prophylactic cranial irradiation has improved the survival outcomes in patients with limited disease. In extensive disease, irinotecan combined with cisplatin has shown promise in improving survival over conventional platinum/etoposide chemotherapy schedules and a confirmatory study is awaited. The future of SCLC treatment may however lie with molecularly targeted therapies, such as antiangiogenesis agents and signal transduction inhibitors, which are being studied at present.

Angiogenesis Inhibitors↗