A phase II randomized study of combined infusional leucovorin sodium and 5- FU versus the leucovorin calcium followed by 5-FU both in combination with irinotecan or oxaliplatin in patients with metastatic colorectal cancer.

BACKGROUND: Leucovorin Sodium (LV/Na) has a high solubility, and is stable when given with continuous infusion of 5-FU. It could maintain significant plasma concentration of 5, 10-meTHF during the whole 5-FU perfusion with the potential of increasing 5-FU cytotoxicity. We conducted a randomized phase II clinical trial on leucovorin calcium (LV/Ca) and LV/Na in metastatic colorectal cancer patients (mCRC). Main objectives were to assess efficacy and safety. PATIENTS AND METHODS: Fifty seven patients with mCRC and no previous chemotherapy for metastatic disease were randomized to receive LV/Na or LV/Ca with irinotecan or oxaliplatine combined with infusional 5-FU. LV/Na was defined as warranting further evaluation in phase III if true overall response rate (ORR) > 35% (α=5%, ß=10% in case of true ORR >55%, 51 evaluable patients planned/arm). RESULTS: Results for LV/Ca and LV/Na arm respectively were: observed ORR, 55% (significantly higher than 35%, p = 0.02) and 61% (p = 0.004). Median overall survival durations were 11.9 months and 22.9 months (p = 0.02) and PFS 8.0 vs. 11.5 months (ns). Grade 3 events were 64% and 46% (p = 0.28). CONCLUSION: Both LV/Na and LV/Ca disclosed an ORR > 35% with comparable safety.

[Malignant peritoneal mesothelioma: a case report]. / Le cas clinique du mois. Mésothéliome péritonéal malin.

I report two cases of malignant peritoneal mesothelioma. Mesothelioma is mostly a pleural disease whether visceral or parietal. Infra-diaphragmatic Mesothelioma accounts for only 10-20% of all mesotheliomas. In over 80% of the cases the pathogenesis is related to asbestos and radiation exposure. However cases with no past history of such exposures appear in the literature. One of our two patients has non past history of exposure to asbestos. In both cases the diagnosis was establishes through both biopsy conducted by laparoscopy and ascites fluid cytology. The disease is most common in males over the age of 40. In case of localised disease cytoreductive surgery using hyperthermic intraperitoneal chemotherapy is recommended. Sadly the disease is often unveiled at an advanced stage requiring palliative chemotherapy usually with a platin derivative or in a small percentage of the cases with abdominal radiotherapy to alleviate pain. Prognosis for patients with malignant peritoneal mesothelioma is very poor with a mean survival of 5,4 months versus 12.5 months for pleural mesothelioma. Peritoneal mesothelioma, although rare, should be considered among the differential diagnosis of ascites differential diagnosis work up.

A Belgian registry of interleukin-2 administration for treatment of metastatic renal cell cancer and confrontation with literature data.

In an effort to map the use of interleukin-2 (IL-2) treatment in patients with clear cell renal cell cancer (RCC) in Belgian hospitals, 44 cases were registered from 9 hospitals between February 2003 and June 2006. It was demonstrated that the majority of these patients were treated with subcutaneous (SC) IL-2. Other methods such as the inhalation of the drug in case of intrathoracic disease or high dose intravenous (IV) administration were much less frequent (3 and 0 cases in this registry, respectively). The results of antitumour activity (around 16% partial response-absence of complete responses) and toxicity of this drug correlate with observations from the literature with the SC administration. In view of the poor results and tolerance with the currently used cytokines (IL-2 or interferon-alfa), much hope is directed towards the development of the novel targeted drugs like sunitinib or sorafenib used alone or in combination with cytokines in this disease.

[Surveillance and side-effects of transfusions]. / Surveillance et effects secondaires des transfusions.

Allogenic blood transfusion may be required for the treatment of anemia due to a hematologic disease, the consequences of chemotherapy or other circumstances, such as haemorrage and/or surgery. Transfusion becomes indispensable to prevent the side effects of anemia, such as hypoxia, palpitations, tachycardia, cardiac ischemia and fatigue. However, frequent transfusions can cause several acute problems such as hemolysis, anaphylactic shock and septic shock but also chronic problems such as iron overload (hemochromatosis), alloimmunisation and metabolic disturbances. Each of these complications can produce serious consequences and could even be sometimes fatal. Therefore we should recognise, prevent and if necessary treat all these hazards. Our article emphasises the potential chronic problems. For hemochromatosis, an iron chelator (deferoxamine) should be administered. In the presence of allo-immunisation the more compatible ABO blood group must be chosen and blood products be eliminated by filtration, when there has been blood reaction. When an allo-graft of hematopoitic tissues is considered an irradiation of blood products is necessary. Research is being carried out to develop substitute products for transfusion (haemoglobine solutions) or molecules acting on the syntheses of haemoglobine (butyrate arginine). The efficacy of erythropoitine, (EPO) is well recognised for stimulation of haemoglobine syntheses in renal failure and oncology.

[How I treat ... sickle cell anemia: current therapies]. / Comment je traite ... une drépanocytose: actualités thérapeutiques.

Vaso-occlusive crisis, thromboembolic events and acute chest syndrome are the most frequent complications in patients with sickle cell disease. Appropriate management of the vaso-occlusive painful crisis includes aggressive analgesia and hydratation. For thromboembolic events, anticoagulation and acetylsalicylic acid with dipyridamole may be considered. Transfusion has a place during some crisis, when hemolysis is increased. Hydroxyurea, a drug that induce foetal hemoglobin synthesis until 30%, has a therapeutic benefit in decreasing the number of vaso-occlusive episodes, of transfusions and that of the acute chest syndrome. Currently, the only treatment that allows definitive cures is familial allogeneic stem cell transplantation. New agents are currently under clinical evaluation such as NO and arginine for aggressive crisis or other aggressive complications and administration magnesium and clotrimazole to prevent intracellular deshydratation. These drugs block cation-transport channels in erythrocyte membranes.

[Malignant tumors of unknown origin]. / Les tumeurs malignes d'origine indéterminée.

Cancers of unknown origin form a specific clinical entity. The diagnostic procedure has to be guided by the therapeutical possibilities and requires a biopsy. Immunohistology, electron microscopy and cytogenetics are informative for carcinomas and poorly differentiated adenocarcinomas. The clinical status and the histology allow the definition of groups of patients who can benefit from a specific therapy and have a better prognosis. For the other patients, the prognosis is severe and there is no efficient therapy available. Such tumors are usually characterized by a very aggressive behaviour.