RGB-02 (biosimilar pegfilgrastim) in the treatment of chemotherapy-induced neutropenia.

Pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. The development and use of biosimilar agents help to rationalize healthcare expenditure and improve access to modern therapies to all who need them. This review focuses on pegfilgrastims with important role in oncology supportive care. RGB-02 (Gedeon Richter) is a proposed biosimilar to pegylated granulocyte-colony stimulating factor (Neulasta®, Amgen) with sustained release properties. The clinical analyses in three randomized clinical studies provided comparative data between RGB-02 and Neulasta, in a Phase III study patients receiving docetaxel-doxorubicin chemotherapy treatment equivalence was found. No difference was detected in any safety measure including immunogenicity; treatment switch, from the reference product to RGB-02 proved safe. Long-acting pegylated filgrastim RGB-02 has successfully accomplished various steps of biosimilar development.

Efficacy and safety of RGB-02, a pegfilgrastim biosimilar to prevent chemotherapy-induced neutropenia: results of a randomized, double-blind phase III clinical study vs. reference pegfilgrastim in patients with breast cancer receiving chemotherapy.

BACKGROUND: Treatment with recombinant human granulocyte-colony stimulating factor (G-CSF) is accepted standard for prevention of chemotherapy-induced neutropenia. RGB-02 (Gedeon Richter) is a proposed biosimilar to pegylated G-CSF (Neulasta®, Amgen) with sustained release properties. This is a randomized, comparative, double-blind, multicenter study to evaluate efficacy and safety of RGB-02 in breast cancer patients receiving cytotoxic regimen. METHODS: Two hundred thirty-nine women presenting with breast cancer were randomized to RGB-02 (n = 121) and the reference product (n = 118). All patients received up to 6 cycles of docetaxel/doxorubicin chemotherapy combination and a once-per-cycle injection of a fixed 6 mg dose of pegfilgrastim. Primary endpoint was the duration of severe neutropenia (ANC < 0.5 × 109/L) in Cycle 1 (2-sided CI 95%). Secondary endpoints included incidence and duration of severe neutropenia (in cycles 2-4), incidence of febrile neutropenia, time to ANC recovery, depth of ANC nadir, and safety outcomes. RESULTS: The mean duration of severe neutropenia in Cycle 1 was 1.7 (RGB-02) and 1.6 days (reference), with a difference (LS Mean) of 0.1 days (95% CI -0.2, 0.4). Equivalence could be established as the CI for the difference in LS Mean lay entirely within the pre-defined range of ±1 day. This positive result was supported by the analysis of secondary endpoints, which also revealed no clinical meaningful differences. Safety profiles were comparable between groups. No neutralizing antibodies against pegfilgrastim were identified. CONCLUSIONS: Treatment equivalence in reducing the duration of chemotherapy induced neutropenia between RGB-02 and Neulasta® could be demonstrated. Similar efficacy and safety profiles of the once-per-cycle administration of RGB-02 and the pegfilgrastim reference were demonstrated. TRIAL REGISTRATION: The trial was registered prospectively, prior to study initiation. EudraCT number ( 2013-003166-14 ). The date of registration was 12 July, 2013.

In vitro effect of carboplatin, cytarabine, paclitaxel, vincristine, and low-power laser irradiation on murine mesenchymal stem cells.

BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) are promising for use in regenerative medicine. Cytostatics can decrease, but low-power laser irradiation (LPLI) can increase the growth of MSCs. The interaction of LPLI, MSCs and cytostatics is not known. This study investigated the effect of four cytostatics (carboplatin, cytarabine, paclitaxel, vincristine), LPLI, and combination of a cytostatic drug and LPLI on murine MSCs (mMSCs). STUDY DESIGN/MATERIALS AND METHODS: MMSCs were exposed to LPLI (660 nm diode laser; 60 mW output power; range of power density: 76-156 mW/cm(2); range of energy density: 1.9-11.7 J/cm(2)) and/or a cytostatic drug (carboplatin: 2, 10, 50; cytarabine: 0.4, 10, 50; paclitaxel: 0.4, 2, 10; vincristine: 0.02, 0.1, 0.5 microg/ml, respectively). Cell proliferation was measured after 24, 48, or 72 hours incubation. RESULTS: LPLI at 1.9 J/cm(2) dose increased the proliferation rate with 41% after 48 hours. However, 11.7 J/cm(2) LPLI caused 42% inhibition and cytostasis was still detectable after 72 hours. LPLI caused equivalent stimulation in single or in divided doses (3.8 vs. double 1.9 J/cm(2) in a 24-hour period). The cytotoxicity of 50 microg/ml carboplatin was eliminated, the inhibitory power of 0.1 microg/ml vincristine was attenuated by 1.9 J/cm(2) LPLI even 3 days post-treatment (attenuation >10%). The 11.7 J/cm(2) LPLI enhanced the cytotoxicity of 50 microg/ml cytarabine (from 48% to 73%) and 10 microg/ml paclitaxel (from 37% to 78%). Combination of the ineffective 0.4 microg/ml cytarabine or paclitaxel with the inhibitory 11.7 J/cm(2) LPLI exhibited stronger inhibition than the 11.7 J/cm(2) LPLI alone (69% and 69% vs. 42%). CONCLUSIONS: Low energy density of LPLI increases and high energy density of LPLI decreases the proliferation of mMSCs. Furthermore, LPLI can prevent or attenuate some drug's cytotoxicity and amplify others'. The result depends on the applied energy density, on the type and concentration of the cytostatics.

[Modern diagnosis and treatment of pancreatic cancer--from the viewpoint of the internist]. / A hasnyálmirigyrák korszeru diagnosztikája és kezelése--belgyógyász onkológus szemmel.

INTRODUCTION: Despite considerable progress in the areas of epidemiology and molecular genetics, pancreatic cancer is still characterized by a dismal prognosis. Pancreatic cancer remains a major unsolved health problem, with conventional cancer treatments having little impact on disease course. AIM: The authors purpose was to offer an overview of the modern diagnosis and treatment of pancreatic cancer for internists and every doctors who are interested in this subject. METHOD: The current literature has been reviewed and summarized. RESULTS AND CONCLUSIONS: Resectability rates and reduction in postoperative mortality are achieved by centralisation of treatment in high-volume speciality centres. For locally advanced, unresectable, and metastatic disease treatment is palliative, however, new methods are being investigated. The current overview provide recommendations for diagnostic and therapeutic algorithms.

[Systemic chemotherapy of liver cancer and patient follow-up]. / A májrák szisztémás kemoterápiája és a betegek gondozása.

We have many possibilities how to treat hepatocellular carcinoma. These therapeutic options depend on the stage of the disease, the condition of the patient and the available therapeutic modalities. At present, none of these treatments are fully successful and the results of systemic treatments are very poor. This paper introduces the role of systemic therapy concerning to prevention, curative and palliative treatments. As well, we emphasize the importance of early diagnosis and patient's follow up.