Pain and cancer cannot be dissociated. A particular feature observed in children is that the child exhibits a certain psychomotor atony with increasing pain. The child complains less and less, making it difficult to recognize the degree of suffering and provide adequate relief. The most painful events for the child are iatrogenic: local care, puncture, injection, infusion, sample taking. The healthcare team must limit such events to the strict minimum.

To determine the extent to which personal characteristics and "person factors" predict symptom distress during the first cycle of chemotherapy.

Angiogenesis, a complex, coordinated process resulting in the assembly and maturation of new blood vessels, is critical for the growth of tumors. Several lines of evidence argue for angiogenesis inhibition in the treatment of colorectal cancer (CRC) : 1) angiogenesis (as measured by microvessel count), and the expression of pro-angiogenesis factors, such as vascular endothelial growth factor (VEGF), the key regulator of normal and pathological angiogenesis, have been reported to correlate with advanced disease and a worse prognosis ; 2) the expression of VEGF has been shown to correlate with RAS mutations, alterations in the APC-WNT signaling pathway, and overexpression of cyclo-oxygenase-2, which all are frequent in CRC ; 3) bevacizumab, a humanized anti-VEGF monoclonal antibody, is a potent inhibitor of tumor growth of various CRC cell lines in murine xenografts ; 4) the addition of bevacizumab to systemic chemotherapy has been shown to be significantly superior to chemotherapy alone in terms of objective tumor response rate, progression-free survival, and overall survival in patients with metastatic CRC, in the frontline, and more recently in the second-line setting, without worsening of chemotherapy-related toxicity. However, several potential specific adverse events, such as thrombosis, hemorrhages, proteinuria, arterial hypertension, and bowel perforations have been described. Whether the antitumoral efficacy of bevacizumab could be increased when combined to low-dose (metronomic) chemotherapy, or radiotherapy (in rectal cancer), is under development, as well other VEGF-targeted approaches (e.g., dominantnegative mutants, antisense oligonucleotides, antibodies directed against VEGF receptors (VEGFR), VEGFR tyrosine kinase inhibitors, soluble VEGFR,...), or other anti-angiogenesis agents (e.g., thalidomide, celecoxib, angiozyme...).

Nowadays, targeting epidermal growth factor-receptor (EGFR) represents an additional therapeutic line for patients with metastatic colorectal cancer (MCRC). Cetuximab, the first available anti-EGFR monoclonal antibody, is approved, combined to irinotecan, in EGFR-positive MCRC after progression while under an irinotecan-based chemotherapy. Other anti-EGFR monoclonal antibodies (panitunumab, matuzumab) are currently evaluated. Preliminary data seem to indicate similar efficacy and toxicity profile to that of cetuximab. Orally available EGFR tyrosine kinase inhibitors (gefitinib, erlotinib, EKB 569) have also been evaluated in patients with MCRC. Preliminary data in terms of clinical activity are not favouring their combination to conventional chemotherapy. Furthermore, they seem to increase the rate of severe haematological and digestive toxicities, especially in patients previously exposed to chemotherapy. At this point of the clinical development of these all EGFR inhibitors (monoclonal antibodies or tyrosine kinase inhibitors) in MCRC, informative data from randomized studies are urgently needed.

Several monoclonal antibodies directed against EGFR are currently in clinical evaluation and include notably the agent cetuximab (C225). Tyrosine kinase inhibitors have chemical structures close to that of ATP and are thus ATP competitors on the tyrosine kinase site (ATP pocket) which is located in the intracellular domain of EGFR (gefitinib and erlotinib, respectively Tarceva and Iressa being the most advanced in clinical development). Well-conducted experimental studies open the way to new clinical applications with the most rewarding currently being the association between cetuximab and irinotecan. The two approaches of EGFR targeting have the same target and similar intracellular molecular impacts but they may differ under several aspects. For instance for the mechanism of action where, for monoclonal antibodies, there is a potential complement of cytotoxic activity brought by the ADCC phenomenon (antibody-directed cell cytotoxicity). One of the main current questions about the clinical use of anti-EGFR drugs is to dispose of faithful predictors for identifying tumors sensitive to this targeted treatment. The agents targeting VEGF are conceptually the same to those applied to EGFR. A major therapeutic advance brought by antiangiogenic drugs in colorectal cancer is attributable to bevacizumab. Bevacizumab is a monoclonal antibody impacting VEGF itself. A controlled clinical trial recently conducted on more than 800 advanced colorectal cancer patients concluded to a significant improvement in both response rate and global survival. This trial was comparing the combination 5FU-leucovorin-bevacizumab to 5FU-leucovorin and the advantage was in favor of the triple combination.

Ifosfamide is an alkylating agent used in the treatment of germ-cell tumors, sarcomas and lymphomas. One of its main side effects is the encephalopathy of which the incidence may reach 30% in the literature, in adults and children just as well.

Bleomycin is an antibiotic with antineoplastic pro prieties. It is used in the traitement of many syndromes. The cutaneous toxicity of bleomycin includes many alteration. We report a case of flagellate erythema following the administration of bleomycin in a 57-year-old women with Kaposi sarcoma. She developped linear lesions 6 days after the first dose of bleomycin. Flagellate erythema is a specific reaction to bleomycin therapy wich occurs in susceptible individuals independently of dose, route of administration and type of malignant disease treated. Its occurs in 10 to 35% of the treated patients.

Chronic myelogenous leukemia is a model for the explaining between dysregulation of tyrosine-kinase and cellular transformation. BCR-ABL protein providing from the abnormal gene is the biological marker of the leukemic cells. It is the molecular counterpart of the chromosomal abnormality that is also called Philadelphia chromosome. Since BCR-ABL drives the leukemic proliferation, it became recently a specific target to develop the tyrosine-kinase inhibitors. These new specific drugs and their effects on the chronic myelogenous leukemia must be taken into account to explain the physiopathology of the disease.

Encephalopathies from 5 fluorouracil (5FU) are rare and generally resolve favorably.

To review and describe the anatomoclinical cases of the endometrial cancers arising on polyps during a hormonotherapy by tamoxifen for breast cancer.

Since last years, the proteasome has emerged as a real and exciting target for anticancer therapy. Velcade (bortezomib, formerly known as PS341) remains the first selective proteasome inhibitor that has demonstrated significant preclinical activity in several tumor models and a significant efficacy in patients with refractory or relapsed multiple myeloma, resulting in an accelerated approval in US and Europe in such a setting. The major biological effect of bortezomib is the inhibition of the nuclear transcription factor NFkappaB, with subsequent inhibition of the growth tumor cells, induction of apoptosis, inhibition of angiogenesis and of cellular adhesion. The better understanding of the role of proteasome in the regulation of tumor cell growth has led to the development of new therapeutic approaches, notably in patients with multiple myeloma but also seems to hold interesting promises in other hematologic malignancies and solid tumors. This review provides a summary of the rationale for using proteasome inhibitors and an update on available and ongoing clinical studies involving human malignancies.

To present the more frequent solid tumors, that require a general anaesthesia and to describe the particularities of the anaesthetic management.

GnRH agonists are derived from the native molecule by substitution of a D-amino acid in position 6 which increases their resistance to enzymatic breakdown and their affinity for LH-RH receptors in comparison with the native hormone. Because of this improved resistance which increases their half-life they have a super-agonistic effect. In 1973, two years only after he characterized LH-RH, A.V. Schally synthesized several GnRH analogs, including D-TRP6-LHRH obtained by substituting the glycine-6 with a D-tryptophan. The biological half life of this agonist injected by the subcutaneous route is 10 times greater than that observed after intravenous injection because of the progressive release of the peptide from the injection site. Pharmaceutical research has led to the development of delayed-release formulations allowing doses to be spaced by intervals of several weeks, or even three months when needed in some indications (Decapeptyl slow release). Triptorelin, as the other GnRH agonists, strongly reduces LH secretion, by preventing the production of the LH-beta subunit. On the opposite, the production of LH-alpha subunit is markedly increased and remains responsive to exogenous GnRH injection, demonstrating that the agonist does not induce actual pituitary desensitization. Compared with LH-RH antagonists which inhibit both LH-alpha and LH-beta subunit secretion, agonists offer the advantage of a sustained efficacy even after one or two days of withdrawal, while the effect of the agonist disappeared as soon as the administration is stopped. On the other hand, GnRH antagonists do not induce the initial hyperstimulation of the gonadotrophs, the so-called flare up, characteristic of the superagonistic effect.

Prostate cancer is currently the main indication of LH-RH analogs. This class, which in recent years has replaced diethylstilbestrol and surgical castration, now plays a major role at all stages of the disease. Numerous studies with contradictory results have compared total hormonal blockage, an alog combined with an anti-androgen, with analog alone in locally advanced prostate cancer. A recent metaanalysis showed a slight though globally non-significant advantage in favour of total blockage, but with a significant advantage in the case of a nonsteroidal anti-androgen. In stage T3 cancers, adjuvant hormone therapy over three years in combination with radiotherapy versus external radiotherapy alone was more effective in terms of local or metastatic progression and survival. Institution during radiotherapy and a prolonged duration of treatment gives a greater benefit though this was only significant for the subgroup of patients with a Gleason score > or = 8. For localized stages but at high risk (PSA > 15 ng / ml and\or Gleason score > 7), adjuvant hormone therapy after prostatectomy improved recurrence-free survival in comparison with prostatectomy followed-up by simple monitoring. On the other hand, the administration of analogs two or three months before radical prostatectomy did not seem to provide any additional benefit. Medical castration prolonged by LH-RH analogs engenders multiple side effects which become all the more worrying as patient survival is prolonged by this hormone therapy. In phase I-II studies, intermittent treatment is equivalent to continuous treatment for "hormone sensitive" patients (PSA nadir at six months < 0.5 ng). Phase III studies are in progress to confirm this equivalence. This intermittent hormone therapy may be a useful solution for elderly patients (> 78 years old) with a biologically highly active cancer and remains to be evaluated in relatively young subjects after radical prostatectomy or radiotherapy. Combination of analogs with chemotherapy has been used very recently for patients who have reached hormonal escape and may be a useful immediate option for patients with cancers with a high risk of progression.