[Granulocyte- colony stimulating factor (G-CSF) use in clinical practice in patients receiving chemotherapy for breast cancer: The Opaline Study]. / Description des modalités pratiques de prescription d'un facteur de croissance de la lignée granulocytaire (G-CSF) chez les patientes recevant une chimiothérapie pour un cancer du sein : étude Opaline.

OBJECTIVES: To describe the French routine use of G-CSF in patients treated for breast cancer as per the EORTC recommendations. PATIENTS AND METHODS: A prospective multicenter observational study conducted between February 2008 and September 2009 in 869 breast cancer patients treated by chemotherapy (CT) and for whom G-CSF treatment will be delivered in primary (PP) or secondary prophylaxis. RESULTS: The mean age was 55 years. A total of 80.3% of CT was in neoadjuvant/adjuvant setting (NAS). PP was delivered in 78.9% of the NAS patients and 67.5% in metastatic situation. Of the 702 evaluable patients, incidences of severe (SN) and febrile neutropenias (FN) in patients who received PP were 9.3% and 4.2%, respectively. In patients who did not received G-CSF at first cycle, SN and FN were 12.4% and 7.3%, respectively. The use of PP was mainly driven by the type of CT for patients treated in the NAS and by patient or disease related risk factors in the locally advanced/metastatic setting. CONCLUSION: This study has shown that the use of G-CSF was in accordance with the 2010 updates of the EORTC recommendations. However, G-CSF appears more widely used in the routine practice.

Phase II trial of pegylated liposomal doxorubicin in combination with gemcitabine in metastatic breast cancer patients.

OBJECTIVE: To assess the efficacy and toxicity of pegylated liposomal doxorubicin combined with gemcitabine as first-line chemotherapy in metastatic breast cancer patients in a phase II trial. PATIENTS AND METHODS: All breast cancer patients with HER2-negative status, hormone refractory tumor, assessable targets, with preserved performance status, and who had not received chemotherapy earlier as treatment for their metastatic disease were eligible. The patients received pegylated liposomal doxorubicin (30 mg/m(2), venous injection, day 1) concurrently with gemcitabine (1000 mg/m(2), venous injection, days 1 and 8), 1 cycle every 3 weeks. RESULTS: Although 38 patients should have been included, this study was prematurely discontinued after recruiting 20 patients because of excessive toxicity: 75% of the patients experienced grade 3 or 4 treatment-related toxicity, including neutropenia, thrombopenia, hand-foot syndrome, and stomatitis, which significantly affected the quality of life. Cardiac toxicity was mild. With regard to efficacy, 50% of the patients (95% confidence interval, 26%-74%) experienced tumor response. The response rate was 40% in patients who had earlier received anthracyclines as adjuvant therapy. Median progression-free survival and median overall survival were 8.8 months and 19 months, respectively. CONCLUSIONS: This combination was efficient, but not well tolerated. From these results, we could not recommend these doses for further assessment and lower doses should be preferred.

Low-molecular-weight heparin (nadroparin) and very low doses of warfarin in the prevention of upper extremity thrombosis in cancer patients with indwelling long-term central venous catheters: a pilot randomized trial.

BACKGROUND AND OBJECTIVES: Upper extremity thrombosis is a major complication of central venous catheters implanted for chemotherapy in cancer patients. Vitamin K antagonists and low-molecular-weight heparins have been recommended in this setting, but their relative benefit-to-risk ratios have never been compared. DESIGN AND METHODS: A prospective, randomized, open, parallel-group, multicenter trial was performed comparing the antithrombotic efficacy and safety of warfarin and the low-molecular-weight heparin, nadroparin, in cancer patients who had undergone central venous catheter implantation. Warfarin was given orally at a fixed daily dose of 1 mg and nadroparin was injected subcutaneously at a fixed daily dose of 2,850 IU for 90 days, or until venographically-confirmed thrombosis occurred. The primary efficacy outcome was the occurrence of upper extremity thrombosis confirmed by venography performed 90 days after insertion of the catheter, or earlier if symptoms of thrombosis had appeared. Safety end-points were bleeding and thrombocytopenia. RESULTS: Fifty-nine patients were included in the study. A total of 21 and 24 patients in the nadroparin and warfarin groups, respectively, were evaluable for primary efficacy. Six out of the 21 patients in the nadroparin group (28.6%) and 4 out of the 24 patients in the warfarin group (16.7%) had venographically-documented upper extremity thrombosis at day 90 (p=0.48). Safety was satisfactory and similar with both treatments. INTERPRETATION AND CONCLUSIONS: Warfarin at a fixed, very low dose and nadroparin at a fixed, prophylactic dose had comparable benefit-to-risk ratios in the prevention of thrombosis associated with central venous catheters in cancer patients.

In-vitro circadian rhythm of murine bone marrow progenitor production.

Hematopoietic processes display 24h rhythms both in rodents and in human beings. We hypothesized these rhythms to be in part generated by a circadian oscillator within the bone marrow. The ability of murine bone marrow granulo-monocytic (GM) precursors to form colonies following colony-stimulating factor (rm GM-CSF) exposure was investigated in liquid culture samples obtained every 3 h for a span of up to 198 h. The CFU-GM count varied rhythmically over the first 4 d of culture, with a reproducible maximum in the early morning hours, similar to that observed in vivo. These experiments provide the first evidence that bone marrow progenitors sustain in vitro circadian rhythmicity, and they demonstrate the presence of a circadian time-keeping system within these cells. The results support the potential usefulness of bone marrow cultures for investigating chronopharmacologic effects of anticancer drugs and cytokines on this target system.