PREMIUM: A French prospective multicenter observational study of factors impacting on efficacy and compliance to cetuximab treatment in first-line KRAS wild-type metastatic colorectal cancer.

BACKGROUND: Cetuximab improves progression-free survival (PFS) and overall survival (OS) in patients with KRAS wild type (wt) metastatic colorectal cancer (mCRC). Few data are available on factors impacting both efficacy and compliance to cetuximab treatment, which is, in combination with chemotherapy, a standard-of-care first-line treatment regimen for patients with KRAS wt mCRC. PATIENTS AND METHODS: PREMIUM is a prospective, French multicenter, observational study that recruited patients with KRAS wt mCRC scheduled to receive cetuximab, with or without first-line chemotherapy, as part of routine clinical practice, between October 28, 2009 and April 5, 2012 (ClinicalTrials.gov Identifier: NCT01756625). The main endpoints were the factors impacting on efficacy and compliance to cetuximab treatment. Predefined efficacy endpoints were PFS and safety. RESULTS: A total of 493 patients were recruited by 94 physicians. Median follow-up was 12.9 months. Median progression-free survival was 11 months [9.6-12]. In univariate analyses, ECOG performance status (PS), smoking status, primary tumor location, number of metastatic organs, metastasis resectability, surgery, folliculitis, xerosis and paronychia maximum grade, and acne preventive treatment were statistically significant. In multivariate analysis (Hazard Ratios of multivariate stepwise Cox models), ECOG PS, surgery, xerosis and folliculitis were positive prognostics factors for longer PFS. Among all patients, 69 (14%) were non-compliant. In multivariate analysis, no variables were statistically significant. The safety profile of cetuximab was consistent with previous studies. CONCLUSIONS: ECOG PS <2, surgical treatment performed, and maximum grade xerosis or folliculitis developed were predictive factors of cetuximab efficacy on KRAS wt mCRC patients. Unfortunately, we failed in identifying predictive factors for compliance in these patients.

[A rare case of bone metastasis from gastro-intestinal stromal tumour: place of radiotherapy]. / À partir d'un cas rare de métastases osseuses d'une tumeur stromale gastro-intestinale : intérêt de la radiothérapie.

Gastro-intestinal stromal tumours are the most common mesenchymal neoplasms of the gastrointestinal tract. Their usual metastatic sites are the liver and the peritoneum, but gastro-intestinal stromal tumours rarely metastasize to the bones. We report the case of a 56-year-old male presenting with bone lesions six years after initial surgical resection. We discuss through this paper the possibilities of management of these lesions and the place of radiotherapy.

[Management of non-small cell lung carcinoma following docetaxel-cisplatin. Results of an epidemiologic survey]. / Prise en charge des cancers bronchiques non à petites cellules après docétaxel-cisplatine. Résultats d'une étude observationnelle.

BACKGROUND: The purpose of this epidemiologic survey was to describe the management of second-line therapy for patients with stage IIIB-IV non-small cell lung carcinoma (NSCLC) following docetaxel-cisplatin as first-line therapy. METHODS: Between June 2003 and December 2004, 265 patients were enrolled. The data registered were the choice of cytotoxics, the safety profile, the efficacy and the clinical benefit. RESULTS: Two hundred and sixty one patients were treated with docetaxel-cisplatin as a first-line regimen and 181 received a second line. This second line was a single agent regimen in 58% of cases and a gemcitabine based treatment in 60.8%. The main criterion for the choice of second-line therapy was the safety profile in 34.3% of cases. The overall response rate was 16.6% after the second line and clinical benefit was reported in 43.6% of patients. CONCLUSION: In more than 2/3 of patients with NSCLC the docetaxel-cisplatin combination leaves the opportunity to give a second-line treatment, providing satisfying results in terms of clinical benefit. In this study gemcitabine was the most widely prescribed second-line treatment, mainly as a single agent.

[Hemolytic uremic syndrome as a complication of gemcitabine treatment: report of six cases and review of the literature]. / Syndrome hémolytique et urémique secondaire à la gemcitabine: à propos de six observations et revue de la littérature.

UNLABELLED: Hemolytic uremic syndrome is a rare condition during gemcitabine therapy. METHODS: We report six new cases of hemolytic uremic syndrome related to gemcitabine, three issued from a retrospective study of 136 consecutive patients treated with gemcitabine for which a systematic screening of this side effect has been performed and 29 cases with clinical data available identified in the literature in order to better characterised frequency and clinical presentation of this side effect. RESULTS: In our series, frequency of HUS is 2.2% and is higher than this previously reported (0.015%) or estimated with the data of clinical trials analysed (0.072 %). For 35 cases with clinical data available, the patients were always treated for a local advanced and/or metastatic disease. For our cases and for literature cases, at the time of diagnosis of hemolytic uremic syndrome, mean number of doses received (mean+/-standard deviation. Minimum/maximum)) (personal cases: 26.5+/-6.6. 16/36, literature cases: 21+/-11. 8/54), cumulative dose received (g/m2) (personal cases : 24.5+/-6.3. 16/31.6, literature cases: 21.7+/-12.4. 2.4/54) and duration of treatment (months) (personal cases: 8.2+/-1.9. 5.6/11, literature cases: 8.5+/-4.0. 3/18) are very closed and high individual variations observed for these factors are not consistent with a time and/or dose dependant toxicity. New-onset hypertension or exacerbation of underlying hypertension is the most common clinical manifestation, with mild anemia; thrombocytopenia is inconstant. The degree of severity of renal failure is highly variable. The existence of subacute clinical form with progressive worsening of the symptoms and biological form at the time of diagnosis suggest the interest of a systematic clinical and biological screening of this side effect, before each injection of gemcitabine. Early prognosis is linked to the evolution of hemolytic uremic syndrome and after hemolytic uremic syndrome healing, cancer progression. Treatment include gemcitabine discontinuation, antihypertensive drugs and if necessary fresh frozen plasma. CONCLUSIONS: Systematic clinical and biological screening of hemolytic uremic syndrome during gemcitabine therapy should allow to better know this complication, to recognize and treat it earlier with a potential positive impact for patients.

[Leiomyosarcoma of the right ventricle]. / Léiomyosarcome cardiaque du ventricule droit.

A 58-year-old woman has dyspnea and palpitations which reveal a leiomyosarcoma of the right ventricle. The medical imaging shows a lobulated sessile tumor attached to the ventricular septum and the tricuspid valve extending into the pulmonary artery trunk. The resection is performed with a tricuspid valvoplasty. In spite of chemotherapy (epirubicin-cyclophosphamide), relapse is observed with pulmonary metastases 17 months after the surgery. The death becomes on 18 months in congestive heart failure. From this case, the authors make a review of the literature about this exceptional tumour, and talk over the low possibilities of treatment, despite the capacities of the new ways of diagnosis.

[Malignant paraganglioma of the uterus]. / Paragangliome malin de l'utérus.

We report a malignant uterine paraganglioma in a 41-year-old woman who underwent a hysterectomy for meno-metrorrhagia. It was initially thought to be a leiomyoma in necrobiosis. The clinical outcome was characterized by an early regional recurrence (in the left Fallopian tube). Later, vertebral and lung metastasis occurred, leading to death 22 months after the initial diagnosis. Paragangliomas are uncommon neuroendocrine tumors, related to pheochromocytomas. They are mainly found in the para-aortic and retroperitoneal region, and less commonly in the pelvic area. Location in the uterus is extremely rare: 5 cases were previously reported and only one malignant.

[Current chemotherapy of locally advanced or metastatic bladder tumors]. / Chimiothérapie actuelle des tumeurs de vessie localement avancées ou métastatiques.

Standard chemotherapy of transitional cell carcinoma of the bladder is actually the combination of cisplatine, methothrexate, vinblastine and doxorubicine (MVAC). Although a high response rate, long term survival are rarely observed. More effective agents without toxicity are necessary. Several agents have demonstrated activity alone or in combinations. Combinations regimens use, paclitaxel, gemcitabine and Gallium nitrate, who prove activity alone or in combination with cisplatine or carboplatine, with a response rate of 40 to 70% in patient with visceral localisations. The optimal regimen is not yet determined.

[Ifosfamide-related encephalopathy. Report of two cases]. / Encéphalopathie à l'ifosfamide. A propos de deux cas.

INTRODUCTION: Due to ifosfamide urotoxicity, encephalopathy is a frequent complication accompanying treatment with this drug. The various clinical, physiological and therapeutical aspects of ifosfamide-related encephalopathy are reviewed. We report two cases and review current literature. EXEGESIS: Ifosfamide-related encephalopathy has polymorphous and non-specific clinical picture. The disease severity is variable, as related deaths have been reported. Clinical signs disappear with treatment discontinuation. Routes of administration, doses, tumoral site and gender have been implicated in the disease physiopathology. Admittedly, metabolite mitochondrial toxicity would be the underlying mechanism. Treatment would be based on intravenous methylene blue. A clinical trial aimed at studying prophylaxis is in progress. A few number of patients have been cured until now. CONCLUSION: Further studies are required to confirm the involved physiopathological mechanisms and methylene blue effects.

[Metastatic pure seminomas of the testicle: role of chemotherapy]. / Séminomes purs métastatiques du testicule: place de la chimiothérapie.

40% of testicular tumours are seminomatous tumours. The low mass tumours (LMT) (stages IIA and IIB of the Royal Mardsen Hospital classification) are usually treated by radiotherapy and the high mass tumours (HMT) (stage IIC, III and IV) by chemotherapy. Chemotherapy regimens are platinum-based polychemotherapy. We report 9 cases of seminomatous testicular tumours (4 LMT and 5 HMT) treated by chemotherapy (BEP modified or CBDCA-etoposide regimens), three courses, with one supplement course if necessary and surgery if residual masses are more than 3 cm long. The rate of complete remission are 100% for LMT and 60% for HMT. This could be an indication to treat in addition with orchidectomy the LMT with chemotherapy and not with radiotherapy (standard-gold) which is more toxic.

[Testicular germ cell tumors]. / Les tumeurs germinales testiculaires.

Testicle germ cells tumors are the most common young men neoplasm. The incidence is maximal in Scandinavian countries. Cryptorchidism is a predisposing factor. Diagnosis is clinic, first treatment is radical orchidectomy by inguinal incision, after study of tumor markers. Histology shows seminoma or non seminomatous tumor. Carcinoma in situ is the precursor of invasive germ cell tumors. Germ cell tumors have no p53 mutation, and have isochrome of the short arm of chromosome 12 as a specific marker. With the results of histological, biochemical and radiographic evaluation, patient are classified as follows: good, intermediate and poor risk prognosis. Standard treatment of stage I seminoma is prophylactic irradiation. Stage II with less than 3 cm lymph node too. Other situations need a cisplatin based chemotherapy. In case of metastatic residuals masses more than 3 cm, surgery need to be discussed. Stage I non seminomatous germ cell tumors are treated by retroperitoneal lymphadenectomy, by surveillance or by two cycles of adjuvant chemotherapy with cisplatin, etoposide and bleomycin (BEP). Standard treatment of good prognosis stage II and III is three cycles of BEP, four for poor prognosis. Residual mass need surgery, adjuvant chemotherapy is necessary in presence of viable germ cell. Standard treatment for relapses is chemotherapy with cisplatin, ifosfamide and vinblastine with a 30% remission rate. The place of high dose chemotherapy with autologous stem cell transplantation is not yet standardised. New drugs, as paclitaxel, are under studies.

[Chronic compartment syndrome]. / Le syndrome chronique des loges.

Among causes of leg pains, a usual disability in athletes, chronic exertional compartment syndrome is far from being uncommon. To the opposite, descriptions concerning the others compartments such as the forearm or thigh are still scarce and poorly documented. A variety of techniques have been described for the measurement of intramuscular pressure. Intramuscular pressure measurement is a valuable and essential tool for diagnosing a compartment syndrome, but it is somewhat controversial when the deep posterior compartment is concerned. Conservative treatment is unsuccessful, whereas surgical decompression yield favorable results; two procedures are performed subcutaneous fasciotomy or open fasciotomy.