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® (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.
Published Studies Related to Novantrone (Mitoxantrone)
A randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated chronic lymphocytic leukaemia. [2011.03]
Combination fludarabine (F), cyclophosphamide (C) and rituximab (R) is the standard front-line therapy in chronic lymphocytic leukaemia (CLL), but appropriate treatment of relapsed/refractory CLL is less clear. Combined FC and mitoxantrone (M) has been reported to be effective in a single arm study, and rituximab when added to chemotherapy in CLL is synergistic...
Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial. [2010.12.11]
BACKGROUND: Although survival of children with acute lymphoblastic leukaemia has improved greatly in the past two decades, the outcome of those who relapse has remained static. We investigated the outcome of children with acute lymphoblastic leukaemia who relapsed on present therapeutic regimens... INTERPRETATION: As compared with idarubicin, mitoxantrone conferred a significant benefit in progression-free and overall survival in children with relapsed acute lymphobastic leukaemia, a potentially useful clinical finding that warrants further investigation. FUNDING: Cancer Research UK, Leukaemia and Lymphoma Research, Cancer Council NSW, and Sporting Chance Cancer Foundation. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
A randomized phase II trial of mitoxantrone, estramustine and vinorelbine or bcl-2 modulation with 13-cis retinoic acid, interferon and paclitaxel in patients with metastatic castrate-resistant prostate cancer: ECOG 3899. [2010.02.24]
BACKGROUND: To test the hypothesis that modulation of Bcl-2 with 13-cis retinoic acid (CRA)/interferon-alpha2b (IFN) with paclitaxel (TAX), or mitoxantrone, estramustine and vinorelbine (MEV) will have clinical activity in men with metastatic castrate-resistant prostate cancer (CRPC)... CONCLUSIONS: Treatment with MEV was well tolerated and demonstrated clinical activity in patients with CRPC. Given the adverse effect of CRA/IFN/TAX on QOL, the study of other novel agents that target Bcl-2 family proteins is warranted. The feasibility of measuring Bcl-2 protein in a cooperative group setting is hypothesis generating and supports further study as a marker for Bcl-2 targeted therapy. TRIAL REGISTRATION: Clinical Trials Registration number: CDR0000067865.
A randomized multicenter phase II clinical trial of mitoxantrone-loaded nanoparticles in the treatment of 108 patients with unresected hepatocellular carcinoma. [2009.12]
Previous studies have demonstrated that intravenous administration of mitoxantrone-loaded polybutylcyanacrylate nanoparticles (DHAD-PBCA-NPs) could allow increased cytotoxicity in hepatic tumors. Therefore, we evaluated the activity and toxicity of DHAD-PBCA-NPs and DHAD injection in individuals with unresected hepatocellular carcinoma...
Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: the EORTC and GIMEMA Groups Study AML-10. [2009.11.10]
PURPOSE: To compare the antitumor efficacy of three different anthracyclines in combination with cytarabine and etoposide in adult patients with newly diagnosed acute myeloid leukemia (AML)... CONCLUSION: In adult patients with AML who do not receive an allogeneic SCT, the use of mitoxantrone or idarubicin instead of daunorubicin enhances the long-term efficacy of chemotherapy.
Clinical Trials Related to Novantrone (Mitoxantrone)
A Study to Evaluate the Safety and Effectiveness of Novantrone Therapy Followed by Copaxone for Multiple Sclerosis. [Completed]
It is thought that treating multiple sclerosis with Novantrone for a short period of time
prior to treatment with Copaxone may enhance the onset effect of Copaxone.
Phase I and Pharmacokinetic Study of Mitoxantrone Hydrochloride Liposome Injection [Completed]
Mitoxantrone � Cetuximab 2nd Line Androgen Independent Prostate Cancer (AIPC) [Active, not recruiting]
To determine the time to progression produced by the combination of Novantrone
(mitoxantrone) and Erbitux (cetuximab) versus Novantrone alone in metastatic AIPC patients
previously treated with docetaxel-based chemotherapy. TTP is defined as time from the start
of treatment date to the date the patient is first recorded as having disease progression,
even in patients who discontinue study treatment early due to toxicity.
Clofarabine, Etoposide, and Mitoxantrone for Relapsed and Refractory Acute Leukemias [Completed]
The purpose of this study is to establish toxicity and a maximum tolerated dose recommended
phase 2 dose of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of
relapsed or refractory acute leukemias. The investigators will observe responses with these
therapy agents and assess the impact of Clofarabine interacting with Etoposide in induction
of DNA strand breaks.
Phase I Study of Weekly Intravenous PS-341 (Bortezomib) Plus Mitoxantrone [Completed]
- Establish the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of weekly
mitoxantrone in combination with weekly PS-341 in patients with advanced AI-PCa.
- Evaluate the effect of bortezomib and mitoxantrone in combination on PSA levels among
patients with baseline PSA levels >/=5 ng/mL who are treated near the maximum tolerated
- Monitor the effect of escalating doses of bortezomib combined with mitoxantrone on
selected parameters of clinical benefit (i. e. performance status, tumor-related
symptoms, measurable disease response).
Reports of Suspected Novantrone (Mitoxantrone) Side Effects
Acute Promyelocytic Leukaemia (21),
Cardiac Failure (12),
Acute Myeloid Leukaemia (10),
Cardiac Failure Congestive (7),
Febrile Neutropenia (6),
Bone Pain (5),
Lung Infection (5),
Pneumonia Fungal (5), more >>
Page last updated: 2011-12-09