A randomized two arm phase III study in patients post radical resection of liver metastases of colorectal cancer to investigate bevacizumab in combination with capecitabine plus oxaliplatin (CAPOX) vs CAPOX alone as adjuvant treatment

<p>Abstract</p> <p>Background</p> <p>About 50% of patients with colorectal cancer are destined to develop hepatic metastases. Radical resection is the most effective treatment for patients with colorectal liver metastases offering five year survival rates between 36-60%. Unfortunately only 20% of patients are resectable at time of presentation. Radiofrequency ablation is an alternative treatment option for irresectable colorectal liver metastases with reported 5 year survival rates of 18-30%. Most patients will develop local or distant recurrences after surgery, possibly due to the outgrowth of micrometastases present at the time of liver surgery. This study aims to achieve an improved disease free survival for patients after resection or resection combined with RFA of colorectal liver metastases by adding the angiogenesis inhibitor bevacizumab to an adjuvant regimen of CAPOX.</p> <p>Methods/design</p> <p>The Hepatica study is a two-arm, multicenter, randomized, comparative efficacy and safety study. Patients are assessed no more than 8 weeks before surgery with CEA measurement and CT scanning of the chest and abdomen. Patients will be randomized after resection or resection combined with RFA to receive CAPOX and Bevacizumab or CAPOX alone. Adjuvant treatment will be initiated between 4 and 8 weeks after metastasectomy or resection in combination with RFA. In both arms patients will be assessed for recurrence/new occurrence of colorectal cancer by chest CT, abdominal CT and CEA measurement. Patients will be assessed after surgery but before randomization, thereafter every three months after surgery in the first two years and every 6 months until 5 years after surgery. In case of a confirmed recurrence/appearance of new colorectal cancer, patients can be treated with surgery or any subsequent line of chemotherapy and will be followed for survival until the end of study follow up period as well. The primary endpoint is disease free survival. Secondary endpoints are overall survival, safety and quality of life.</p> <p>Conclusion</p> <p>The HEPATICA study is designed to demonstrate a disease free survival benefit by adding bevacizumab to an adjuvant regime of CAPOX in patients with colorectal liver metastases undergoing a radical resection or resection in combination with RFA.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier NCT00394992</p

Activity of a new antiemetic agent: alizapride. A randomized double-blind crossover controlled trial

Alizapride is a methoxy-2-benzamide derivative three times more potent than its parent compound, metoclopramide, as an antagonist of apomorphine-induced emesis in dogs. The antiemetic activity of alizapride plus dexamethasone (DXM) was compared with that of placebo plus DXM in a randomized, double-blind, crossover study in cancer patients receiving cisplatin (DDP). Alizapride, given at the maximally tolerated dose of 4 mg/kg x 5, or placebo was given in a sequence determined by randomization during two successive, identical courses of antitumor chemotherapy. The antiemetic treatment was given 30 min before and 1.5, 3.5, 5.5, and 7.5 h after starting. DXM, in a dose of 12 mg, was given IV with the first administration of alizapride or placebo. A total of 39 patients completed the two courses of chemotherapy. The severity of gastrointestinal symptoms was influenced by previous treatment but not by the treatment sequence. Although our overall results suggest that alizapride does not add to the activity of DXM against DDP-induced amesis, a statistically significant difference favoring alizapride plus DXM was found among patients with the lowest gastrointestinal tolerance to DDP: women, patients under 50 years of age, and patients pretreated with chemotherapy including DDP and non-DDP agents. Side effects consisted of orthostatic hypotension, which was symptomatic in two patients, and a single occurrence of severe extrapyramidal syndrome. We conclude that alizapride is more active than placebo when combined with DXM for DDP-induced emesis in patients at high risk of severe nausea and vomiting. The severity of the side effects in this study indicates that a dose reduction of alizapride might be appropriate for further studies.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Phase II study of a combination of hydroxyurea, fluorouracil and mitomycin in previously treated squamous cell carcinoma of the head and neck

Thirty-six evaluable patients with locoregionally recurrent or metastatic squamous cell carcinoma of the head and neck were treated with a combination of mitomycin (10 mg/m2 i.v. day 1), fluorouracil (500 mg/m2 i.v. days 1 + 8) and hydroxyurea (1 g/m2 orally days 2-14). Thirty-three patients had received prior radiation therapy and 34 prior chemotherapy. Only two patients exhibited a partial response. Hematological toxicity was substantial, with three patients experiencing leukopenia below 1000/mm3 and seven patients experiencing thrombocytopenia below 25,000/mm3. There were four cases of treatment-related bleeding and one infection. Other side-effects were mild to moderate. Low antitumor activity and substantial toxicity preclude further evaluation of this regimen in head and neck cancer. © 1986.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Phase II study of epirubicin in advanced adenocarcinoma of the pancreas

The EORTC Gastrointestinal Group has conducted a phase II trial in 41 patients with locally advanced or metastatic adenocarcinoma of the pancreas with epirubicin 90 mg/m2 intravenously every 4 weeks, with dose escalation if possible. Seven patients were not evaluable for response. In 34 evaluable patients there were two complete and six partial responses (response rate 24%). Nine patients had stable disease for at least 2 months, including one patient with a minor response. Median time to progression for responders was 7 months, for all patients 3 months. Median survival for responders was 9 months, for all patients 5 months. It is concluded that epirubicin is an active drug in pancreatic cancer. © 1985.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

EUROSCAN, a randomized trial of vitamin A and N-Acetylcysteine in patients with head and neck cancer or lung cancer

info:eu-repo/semantics/publishe

Differential sensitivity of normal marrow myeloid progenitor cells to mitoxantrone and bisantrene

info:eu-repo/semantics/publishe

The value of preoperative radiotherapy in esophageal cancer: Results of a study of the E.O.R.T.C.

Attempts to combine radiation therapy and surgery in patients with operable carcinoma of the esophagus began 30 years ago. The first reported surgical series showed a low rate of resectability and a high postoperative mortality. Results of radiation therapy alone were also disappointing in the long run, especially in patients who appeared to be excellent operative risks with small localized tumors. The rationale for a combined approach was that x-ray therapy could bring about a reduction of tumor activity and bulk, an improvement in nutritional state through the restoration of the ability to swallow, a reduction of transplantability of the tumor, and a curative effect on periesophageal regional disease which is not treated well by surgery. On the other hand, surgery often allowed an extended resection, clearing residual foci or distant esophageal wall extension. The limit of a combined approach is the toxicity of the preoperative radiation which must be mild enough to allow surgery to proceed without excessive delay or increased mortality. Numerous radiotherapy schedules were tried using different fields, doses, and fractionations, most of them in nonrandomized studies. Two prospective randomized trials have been recently reported. The final results of a third prospective trial, run by the E.O.R.T.C. will be presented. © 1987 Société Internationale de Chirurgie.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

An EORTC gastrointestinal group phase II evaluation of epirubicin combined with 5-fluorouracil in advanced adenocarcinoma of the pancreas

The EORTC Gastrointestinal Group has conducted a phase II trial in 47 patients with locally advanced or metastatic adenocarcinoma of the pancreas with epirubicin 90 mg/m2 intravenously on day 1 in combination with 5-fluorouracil 500 mg/m2 in a 2 hr infusion day 1-4, every 4 weeks. Of 43 evaluable patients there were six early deaths due to tumour progression and one due to a cerebrovascular accident. There were six partial responses for a response rate of 14% including early deaths. The median survival for all patients was 4 months. It is concluded that the addition of 5-fluorouracil to epirubicin does not appear to enhance the therapeutic results of epirubicin alone. © 1987.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

INTEREST RATE PASS-THROUGH IN THE COMMON MONETARY AREA OF THE SACU COUNTRIES

We investigate the interest rate pass-through in the four Common Monetary Area (CMA) countries of the South African Customs Union (SACU). We employ an empirical pass-through model that allows for thresholds, asymmetric adjustment, and structural changes. We show that CMA bank lending markets exhibit quite some degree of homogenization as the pass-through is often fast and complete. Deposit markets are somewhat more heterogeneous by showing differing degrees of interest rate stickiness and asymmetric adjustment. Policy makers should therefore be concerned about imperfect competition which may be at the heart of the remaining cross-country differences in monetary transmission in the CMA. Copyright (c) 2006 The Authors. Journal compilation (c) 2006 Economic Society of South Africa.