ever in absence of infection 15 14 7 6
Weight gain 15 14 16 15
Abnormal creatinine 14 13 11 10
Other gastrointestinal 13 14 11 11
Vomiting 12 11 6 5
Other neurologic 11 11 5 5
Hypocalcemia 10 10 5 5
Hematuria 9 11 5 6
Hyponatremia 9 9 3 3
Sweats 9 9 2 2
Other liver 8 8 8 8
Stomatitis 8 8 1 1
Cardiac dysrhythmia 7 7 3 3
Hypokalemia 7 7 4 4
Neuro/constipation 7 7 2 2
Neuro/motor disorder 7 7 3 3
Neuro/mood disorder 6 6 2 2
Skin disorder 6 6 4 4
Cardiac ischemia 5 5 1 1
Chills 5 5 0 0
Hemorrhage 5 5 3 3
Myalgias/arthralgias 5 5 3 3
Other kidney/bladder 5 5 3 3
Other endocrine 5 6 3 4
Other pulmonary 5 5 3 3
Hypertension 4 4 5 5
Impotence/libido 4 7 2 3
Proteinuria 4 6 2 3
Sterility 3 5 2 3
N= Novantrone, H= hydrocortisone
General
Allergic Reaction
Hypotension, urticaria, dyspnea, and rashes have been reported occasionally. Anaphylaxis/anaphylactoid reactions have been reported rarely.
Cutaneous
Extravasation at the infusion site has been reported, which may result in erythema, swelling, pain, burning, and/or blue discoloration of the skin. Extravasation can result in tissue necrosis with resultant need for debridement and skin grafting. Phlebitis has also been reported at the site of the infusion.
Hematologic
Topoisomerase II inhibitors, including Novantrone, in combination with other antineoplastic agents or alone, have been associated with the development of acute leukemia (see WARNINGS).
Leukemia
Myelosuppression is rapid in onset and is consistent with the requirement to produce significant marrow hypoplasia in order to achieve a response in acute leukemia. The incidences of infection and bleeding seen in the U.S. trial are consistent with those reported for other standard induction regimens.
Hormone-Refractory Prostate Cancer
In a randomized study where dose escalation was required for neutrophil counts greater than 1000/mm3, Grade 4 neutropenia (ANC < 500 /mm3) was observed in 54% of patients treated with Novantrone + low-dose prednisone. In a separate randomized trial where patients were treated with 14 mg/m2, Grade 4 neutropenia in 23% of patients treated with Novantrone + hydrocortisone was observed. Neutropenic fever/infection occurred in 11% and 10% of patients receiving Novantrone + corticosteroids, respectively, on the two trials. Platelets < 50,000/mm3 were noted in 4% and 3% of patients receiving Novantrone + corticosteroids on these trials, and there was one patient death on Novantrone + hydrocortisone due to intracranial hemorrhage after a fall.
Gastrointestinal
Nausea and vomiting occurred acutely in most patients and may have contributed to reports of dehydration, but were generally mild to moderate and could be controlled through the use of antiemetics. Stomatitis/mucositis occurred within 1 week of therapy.
Cardiovascular
Congestive heart failure, tachycardia, EKG changes including arrhythmias, chest pain, and asymptomatic decreases in left ventricular ejection fraction have occurred. (See WARNINGS)
Pulmonary
Interstitial pneumonitis has been reported in cancer patients receiving combination chemotherapy that included
