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Marc Debled

Publications and source records attributed to Marc Debled.

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When will more useful predictive factors be ready for use?

Adjuvant chemotherapy is widely used, but its performance is not optimal. Two subgroups of patients do not get any benefit from adjuvant chemotherapy: the first one comprises patients who are already cured by locoregional treatment alone and the second one patients who do not profit from adjuvant chemotherapy because of resistance to the regimens employed. To improve the cost/benefit of this treatment strategy, we have two means: one is to improve the sensitivity of prognostic factors to be able to select a specific group with a good signature that does not need adjuvant treatment; the second is to identify predictive factors that may help us to select the optimal therapeutic strategy or the optimal regimen or drug for individual patients. New technologies of microarray revealed several genetic profiles. A large randomized trial (Microarray In Node-negative Disease may Avoid ChemoTherapy, MINDACT) will compare the information obtained with the genomic profiling and the classical clinico-pathologic index (St Gallen); the objective is to allow women not to be treated with adjuvant chemotherapy if their genomic signature is good. Another trial (EORTC 10994) is conducted in order to show that in cases of p53 mutated tumors, neoadjuvant chemotherapy with docetaxel is more efficient than an anthracycline-containing regimen. A supplementary study will evaluate gene profile predicting for p53 status. So, new genomic prognostic factors are still in development and seem very promising for optimizing the indications for adjuvant chemotherapy.

Breast Neoplasms↗

Intense paraneoplastic neutrophilic leukemoid reaction related to a G-CSF-secreting lung sarcoma.

A white blood cell count more than 50 x 10(9)/l, not related to bone marrow involvement, is termed leukemoid reaction. We report on the first case of an undifferentiated sarcoma of the lung associated with an intense paraneoplastic neutrophilic leukemoid reaction related to the production of granulocyte colony-stimulating factor (G-CSF). A radiography and a computed tomography scan of the chest revealed a well-limited voluminous and heterogeneous low-density mass of the left lung. The patient died of multiorgan failure related to uncontrolled progressive tumor growth after admission and two cycles of chemotherapy. The patient's G-CSF serum concentration was dramatically elevated (6,538 pg/ml) compared to serum levels observed in normal controls and patients with elevated leukocytosis (31 and 387 pg/ml, respectively). The G-CSF concentration dramatically increased after the first cycle of chemotherapy and during the subsequent neutropenia, as a result of the tumor lyses as well as of disruption of the physiological negative feedback mechanism. Adjunction of the patient's serum to CD34+ cell cultures induced a 12.3-fold increase in CD15+ cells, demonstrating the serum's capacity to induce myeloid differentiation.

Cell Proliferation↗

Hypocalcemia following pamidronate administration for bone metastases of solid tumor: three clinical case reports.

Bisphosphonates, such as pamidronate, are a new class of drugs, initially described for treatment of neoplasic hypercalcemia. Currently, they also may be used in the treatment of bone metastases from solid tumor, even without hypercalcemia. Hypocalcemia is a potential adverse effect of these drugs, which is considered infrequent and rarely symptomatic. We describe three cases of severe hypocalcemia following one injection of pamidronate. The three patients had bone metastases from solid tumors (breast in two cases, prostate in one), at least partially osteoblastic, and none had hypercalcemia. The induced hypocalcemia was rapid in onset, severe, and durable. The mechanism seems to be multiple and may include both the expected reduction of osteolysis and also a rapid and direct action on parathyroid glands followed by resistance to parathormone. Some elements could amplify the phenomenon, such as latent hypoparathyroidism after surgery, cervical radiotherapy, hypomagnesemia, or low 25 hydroxy vitamin D (25OH D). For patients who have such risk factors, it may be useful to check calcium several days after the first injection.

Antineoplastic Agents↗