BOXED WARNING SECTION
NOVANTRONE® (mitoxantrone for injection concentrate) should be administered under the supervision of a physician experienced in the use of cytotoxic chemotherapy agents.
NOVANTRONE® should be given slowly into a freely flowing intravenous infusion. It must never be given subcutaneously, intramuscularly, or intra-arterially. Severe local tissue damage may occur if there is extravasation during administration. (See ADVERSE REACTIONS, General, Cutaneous and DOSAGE AND ADMINISTRATION, Preparation and Administration Precautions ).
NOT FOR INTRATHECAL USE. Severe injury with permanent sequelae can result from intrathecal administration. (See WARNINGS, General)
Except for the treatment of acute nonlymphocytic leukemia, NOVANTRONE® therapy generally should not be given to patients with baseline neutrophil counts of less than 1,500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving NOVANTRONE®.
Use of NOVANTRONE® has been associated with cardiotoxicity. Cardiotoxicity can occur at any time during NOVANTRONE® therapy, and the risk increases with cumulative dose. Congestive heart failure (CHF), potentially fatal, may occur either during therapy with NOVANTRONE® or months to years after termination of therapy. All patients should be carefully assessed for cardiac signs and symptoms by history and physical examination prior to start of NOVANTRONE® therapy. Baseline evaluation of left ventricular ejection fraction (LVEF) by echocardiogram or multi-gated radionuclide angiography (MUGA) should be performed. Multiple sclerosis patients with a baseline LVEF <50% should not be treated with NOVANTRONE®. LVEF should be reevaluated by echocardiogram or MUGA prior to each dose administered to patients with multiple sclerosis. Additional doses of NOVANTRONE® should not be administered to multiple sclerosis patients who have experienced either a drop in LVEF to below 50% or a clinically significant reduction in LVEF during NOVANTRONE® therapy. Patients with multiple sclerosis should not receive a cumulative dose greater than 140 mg/m2. In cancer patients, the risk of symptomatic congestive heart failure (CHF) was estimated to be 2.6% for patients receiving up to a cumulative dose of 140 mg/m2. Presence or history of cardiovascular disease, prior or concomitant radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, or concomitant use of other cardiotoxic drugs may increase the risk of cardiac toxicity. Cardiac toxicity with NOVANTRONE® may occur whether or not cardiac risk factors are present. For additional information, see WARNINGS, Cardiac Effects, and DOSAGE AND ADMINISTRATION.
Secondary acute myelogenous leukemia (AML) has been reported in multiple sclerosis and cancer patients treated with mitoxantrone. In a cohort of mitoxantrone treated MS patients followed for varying periods of time, an elevated leukemia risk of 0.25% (2/802) has been observed. Postmarketing cases of secondary AML have also been reported. In 1774 patients with breast cancer who received NOVANTRONE® concomitantly with other cytotoxic agents and radiotherapy, the cumulative risk of developing treatment-related AML, was estimated as 1.1% and 1.6% at 5 and 10 years, respectively (see WARNINGS section). Secondary acute myelogenous leukemia (AML) has been reported in cancer patients treated with anthracyclines. NOVANTRONE® is an anthracenedione, a related drug.
The occurrence of refractory secondary leukemia is more common when anthracyclines are given in combination with DNA-damaging antineoplastic agents, when patients have been heavily pretreated with cytotoxic drugs, or when doses of anthracyclines have been escalated.
|
| |
NOVANTRONE SUMMARY
NOVANTRONE® (mitoxantrone hydrochloride) is a synthetic antineoplastic anthracenedione for intravenous use.
NOVANTRONE® is indicated for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (i.e., patients whose neurologic status is significantly abnormal between relapses). NOVANTRONE® is not indicated in the treatment of patients with primary progressive multiple sclerosis.
The clinical patterns of multiple sclerosis in the studies were characterized as follows: secondary progressive and progressive relapsing disease were characterized by gradual increasing disability with or without superimposed clinical relapses, and worsening relapsing-remitting disease was characterized by clinical relapses resulting in a step-wise worsening of disability.
NOVANTRONE® in combination with corticosteroids is indicated as initial chemotherapy for the treatment of patients with pain related to advanced hormone-refractory prostate cancer.
NOVANTRONE® in combination with other approved drug(s) is indicated in the initial therapy of acute nonlymphocytic leukemia (ANLL) in adults. This category includes myelogenous, promyelocytic, monocytic, and erythroid acute leukemias.
|
NEWS HIGHLIGHTS
Published Studies Related to Novantrone (Mitoxantrone)
Survival and PSA response of patients in the TAX 327 study who crossed over to receive docetaxel after mitoxantrone or vice versa. [2008.10]
BACKGROUND: The TAX 327 study compared 3-weekly docetaxel, weekly docetaxel or 3-weekly mitoxantrone, each with prednisone, for 1006 patients with metastatic hormone-refractory prostate cancer. Survival and symptom control were superior following 3-weekly docetaxel as compared with mitoxantrone. At progression, many patients were treated with the other drug. Here, we provide a retrospective report of survival and prostate-specific antigen (PSA) response after second-line therapy... CONCLUSIONS: One quarter of men received crossover therapy and survival was similar in the crossover groups. The PSA response rate to docetaxel after mitoxantrone was higher than that for mitoxantrone after docetaxel.
Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. [2008.01.10]
PURPOSE: The TAX 327 study compared docetaxel administered every 3 weeks (D3), weekly docetaxel (D1), and mitoxantrone (M), each with prednisone (P), in 1,006 men with metastatic hormone-resistant prostate cancer (HRPC). The original analysis, undertaken in August 2003 when 557 deaths had occurred, showed significantly better survival and response rates for pain, prostate-specific antigen (PSA), and quality of life for D3P when compared with MP. Here, we report an updated analysis of survival... CONCLUSION: The present analysis confirms that survival of men with metastatic HRPC is significantly longer after treatment with D3P than with MP. Consistent results are observed across subgroups of patients.
[Cognitive impact of mitoxantrone and methylprednisolone in multiple sclerosis: an open label study] [2008.01]
Interferons beta have shown some positive effects on cognitive function in multiple sclerosis (MS).We suggest that mitoxantrone combined with methylprednisolone has a potential positive effect on cognitive functions.
Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. [2007.05.20]
PURPOSE: Rituximab has been shown to be active in follicular lymphoma (FL), both as monotherapy and in combination with chemotherapy. We conducted a randomized trial comparing mitoxantrone, chlorambucil, and prednisolone (MCP) chemotherapy plus rituximab with MCP alone... CONCLUSION: The R-MCP regimen significantly improves complete and overall response rates, EFS, PFS, and OS in patients with previously untreated advanced FL, without a clinically significant increase in toxicity.
Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). [2006.12.15]
In follicular lymphoma (FL) and mantle cell lymphoma (MCL) the monoclonal antibody rituximab (R) improves the prognosis when combined with chemotherapy... Hence, R-maintenance is effective after salvage with R-chemotherapy and significantly prolongs response duration in patients with recurring or refractory FL or MCL.
Clinical Trials Related to Novantrone (Mitoxantrone)
Phase II Study of Novantrone(R) (Mitoxantrone) and Etoposide in Patients With HIV Associated Large Cell and Immunoblastic Lymphomas [Completed]
To determine the efficacy and toxicity of the combination of mitoxantrone hydrochloride (
Novantrone ) and etoposide in the treatment of patients with HIV associated lymphomas.
A Study of the Safety and Efficacy of CNTO 328 in Patients With Metastatic Hormone-Refractory Prostate Cancer (HRPC) [Suspended]
This study has two parts. The purpose of this part 1 of the study is to determine whether it
is safe to administer CNTO 328 in combination with mitoxantrone and prednisone in patients
with metastatic hormone- refractory prostate cancer (HRPC).The main purpose of the part 2
study is to assess the effects (good and bad) of CNTO 328 when given in combination with
mitoxantrone and prednisone to patients with metastatic hormone-refractory prostate cancer.
Fludarabine, Mitoxantrone, and Dexamethasone (FND) Plus Rituximab for Lymphoma Patients [Active, not recruiting]
Primary Objectives:
1. To compare molecular response rates with the FND regimen followed by rituximab (chimeric
anti-CD20 antibody) and interferon versus FND plus rituximab concurrently, followed by
interferon, for patients with stage IV indolent lymphoma.
2. To compare the toxicity of these two regimens, including their effects on B- and T-cell
subsets, immunoglobulins, and patterns of infections.
3. To compare failure-free and overall survival rates with these two regimens.
4. To identify and treat with a separate strategy those follicular lymphoma patients
without bcl-2 mbr or mcr gene rearrangement ("germline" patients) because of their
adverse outcome with FND alone in our prior experience.
Mitoxantrone, Prednisone Plus Sorafenib in Taxane-Refractory Metastatic Hormone Refractory Prostate Cancer (HRPC) [Active, not recruiting]
The purpose of this research study is to determine if the combination of mitoxantrone,
prednisone and sorafenib will improve the time to progression of advanced stage metastatic
hormone-refractory prostate cancer.
Phase II Study of Intravenous Novantrone(R) in the Treatment of AIDS Related Kaposi's Sarcoma [Completed]
|
|
|
|
Page last updated: 2008-11-03
|
