Myotax: a phase II trial of docetaxel plus non-pegylated liposomal doxorubicin as first-line therapy of metastatic breast cancer previously treated with adjuvant anthracyclines.

AIM: Non-pegylated liposomal doxorubicin (NPLD) has demonstrated equivalent antitumour activity to conventional doxorubicin and a significantly lower risk of cardiotoxicity when given as a single agent or in combination with cyclophosphamide. This phase II trial was performed to evaluate the efficacy and the safety of NPLD and docetaxel combination in patients with metastatic breast cancer previously exposed to adjuvant anthracyclines. PATIENTS AND METHODS: Thirty-four patients received NPLD 60 mg/m(2) and docetaxel 75 mg/m(2) in a 21-day cycle as first-line therapy of metastatic breast cancer. Treatment was planned for six cycles and was continued until progression or toxicity. RESULTS: Objective response rate among response-assessable patients was 79% (95% CI (confidence interval), 64-94%) and 27% (95% CI, 11-43%) presented a complete response. Median progression free survival was 11.3 months (95% CI, 6.2-13.3 months) and median overall survival was 28.2 months (95% CI, 16-36.4 months). Symptomatic grade 3 cardiotoxicity occurred in 15% of cases and febrile neutropenia in 47% of the patients. CONCLUSIONS: The combination of NPLD and docetaxel demonstrated high antitumour activity in a population of metastatic breast cancer patients exposed to adjuvant anthracyclines and showed an unexpected and unexplained 15% symptomatic left ventricular systolic dysfunction rate.

[Immunodepression and pulmonary infections]. / Immunodépression et infections pulmonaires.

The acquired immunosuppressed states are increasingly numerous. Pneumopathies are a frequent, serious complication and etiologic diagnosis is often difficult. The nature of the micro-organism in question is a function of the immunizing type of deficiency. In neutropenias, the infections are primarily bacterial, their potential gravity being correlated with the depth of the deficiency into polynuclear, or fungic, especially in prolonged neutropenias. The aspleened states are responsible for a deficit of the macrophage system and contribute to the infections with encapsulated germs (pneumococci, klebsiellas...). The organic grafts imply an attack of cell-mediated immunity, in the particular case of the auxiliary T lymphocytes (CD4)), with a special predisposition for viral and fungic infections. During VIH infection, the immunizing deficit of CD4 lymphocytes worsens with time. At the early stage, the infections are especially bacterial. At the more advanced stages, the pulmonary pneumocystosis and tuberculosis dominate. At the late stage, finally, deep immunosuppression allows emerging of the atypical mycobacteries. In the deficiencies of humoral immunity (congenital hypogammaglobulinemias, lymphoid hemopathies B), the germs to be mentioned are the pneumococcus, Haemophilus influenzae, the salmonellas and the legionellas. Immunosuppressed pneumopathies are characterized by radio-clinical pictures of very variable gravity, ranging from focused acute pneumopathy to bilateral diffuse pneumopathy with acute respiratory distress syndrome, with phases of atypical tables with respiratory symptomatology larval or absent. The highlighting of the micro-organisms in question requires urgent complementary investigations: hemocultures, bronchiolo-alveolar washing. In certain cases, it will be possible to resort to the transtracheal puncture or transthoracic puncture guided by tomodensitometry, and if necessary to pulmonary biopsy under videothoracoscopy. Emergency of the anti-infectious treatment imposes, in general, a presumptive treatment directed according to the immunizing deficiency in question and etiologic suspicion. It will be associated, if necessary, with urgent measurements of respiratory intensive care.

[Cytomegalovirus myeloradiculitis in pregnancy]. / Myéloradiculite à cytomégalovirus au cours d'une grossesse.

INTRODUCTION: Cytomegalovirus neurological complications are frequent in immunocompromised patients specially in HIV positive patient. In immunocompetent patient these complications are infrequent. EXEGESIS: We describe a case of cytomegalovirus myeloradiculitis during pregnancy in a 25-year-old woman, HIV negative. The evolution was favorable with foscarnet therapy. CONCLUSION: A spinal complication during cytomegalovirus infection in immunocompetent patient should lead to a therapy with a specific antiviral to reduce neurologic involvement.

[Meningoradiculitis revealing an occult medulloblastoma-PNET in an adult]. / Méningo-radiculite révélant un médulloblastome-PNET occulte de l'adulte.

Neoplastic meningitis as the presentation of occult primitive neuroectodermal tumor (PNET) is occasionally described in children. We report the case of an 64 year old-man who presented a meningo-radiculopathy with progressive injury of the cauda equina and then the ocular motor nerves, revealing an occult medulloblastoma-PNET.

Listeriosis after fludarabine treatment for chronic lymphocytic leukemia.

The authors report a case of Listeria monocytogenes septicemia in a patient with advanced CLL after a single course of fludarabine, without any other immunosuppressive therapy e.g. corticosteroids. The immunosuppressive action of fludarabine in patients who are already severely immunosuppressed must be considered from a diagnostic and therapeutic point of view. Listeriosis and other opportunistic infections, like pneumocystis carinii pneumonia, have been reported during and after treatment with purine analogues. Prophylaxis with cotrimoxazole must therefore be discussed in patients with CLL treated with fludarabine.

[Intensive chemotherapy with autologous stem cell transplantation in ovarian cancers: analysis of 67 patients treated at the Paoli-Calmettes Institute and a review of the literature]. / Chimiothérapie intensive avec autogreffe de cellules souches hématopoïétiques dans le cancer de l'ovaire: analyse de 67 patientes traitées à l'institut Paoli-Calmettes et revue de la littérature.

Despite important initial chemosensitivity, advanced ovarian cancer has a bad prognosis with a median survival of 20 to 30 months. These results might be better with intensive chemotherapy. We analysed 67 patients treated by intensive chemotherapy with autologous stem cell transplantation for advanced ovarian cancer at Institute Paoli-Calmettes between 1980 and 1994. Population was divided in two groups: salvage group (n = 30) for initial chemotherapy-refractory patients and consolidation group (n = 37) for sensitive patients. Several successive conditioning regimens were used, all based on alkylating agents. Principal toxicities were severe aplasia and mucositis. Four patients died from toxicity related to infection during strong immunosuppression. In salvage group, 9 out of 21 evaluable patients responded (43%), but duration of responses was short (median range of 5 months) and 2-year overall survival rate was 8% after transplantation. In consolidation group, 19 patients are alive and 15 are without disease progression with a median follow-up of 42 months (17, 161) after diagnosis. Five-year disease-free survival rate is 28% (median range of 35 months) and 5-year overall survival rate is 48% (median range of 41 months). Intensification does not seem to be long term beneficial for initial chemotherapy refractory patients, despite objective responses rate better than classical treatment. On the other hand, results seem better than conventional treatments in case of chemosensitive disease and should be confirmed prospectively in larger cohort of patients. Moreover, other research directions are open like intensification supported by hematopoietic growth-factors and peripheral stem cells, definition of best conditioning regimen, use of taxanes, and intensification in first line chemotherapy after initial surgery.