Event MP
(n = 21) N + MP
(n = 21)
N = Novantrone, MP = methylprednisolone.
*  Assessed using National Cancer Institute (NCI) common toxicity criteria.
a.  < 4000 cells/mm3
b.  < 1500 cells/mm3
c.  < 100,000 cells/mm3
WBC low a 14 100
ANC low b 10 100
Lymphocytes low 43 95
Hemoglobin low 48 43
Platelets low c 0 33
SGOT high 5 15
SGPT high 10 15
Glucose high 5 10
Potassium low 0 10
N = Novantrone, MP = methylprednisolone
*  Assessed using National Cancer Institute (NCI) common toxicity criteria.
a.  < 4000 cells/mm3
b.  < 1500 cells/mm3
c.  < 100,000 cells/mm3
WBC low a 14 100
ANC low b 10 100
Lymphocytes low 43 95
Hemoglobin low 48 43
Platelets low c 0 33
SGOT high 5 15
SGPT high 10 15
Glucose high 5 10
Potassium low 0 10

Leukopenia and neutropenia were reported in the N +MP group (see Table 5b).  Neutropenia occurred within 3 weeks after Novantrone administration and was always reversible.  Only mild to moderate intensity infections were reported in 9 of 21 patients in the N +MP group and in 3 of 21 patients in the MP group; none of these required hospitalization.  There was no difference among treatment groups in the incidence or severity of hemorrhagic events.  There were no withdrawals from Study 2 for safety reasons.

Leukemia

Novantrone has been studied in approximately 600 patients with acute non-lymphocytic leukemia (ANLL).  Table 6 represents the adverse reaction experience in the large U.S. comparative study of mitoxantrone + cytarabine vs daunorubicin + cytarabine.  Experience in the large international study was similar.  A much wider experience in a variety of other tumor types revealed no additional important reactions other than cardiomyopathy (see WARNINGS).  It should be appreciated that the listed adverse reaction categories include overlapping clinical symptoms related to the same condition, e.g., dyspnea, cough and pneumonia.  In addition, the listed adverse reactions cannot all necessarily be attributed to chemotherapy as it is often impossible to distinguish effects of the drug and effects of the underlying disease.  It is clear, however, that the combination of Novantrone + cytarabine was responsible for nausea and vomiting, alopecia, mucositis/stomatitis, and myelosuppression.

Table 6 summarizes adverse reactions occurring in patients treated with Novantrone + cytarabine in comparison with those who received daunorubicin + cytarabine for therapy of ANLL in a large multicenter randomized prospective U.S. trial.

Adverse reactions are presented as major categories and selected examples of clinically significant subcategories.

Table 6 Adverse Events Occurring in ANLL Patients Receiving Novantrone or Daunorubicin  Induction     Consolidation
 [% pts entering induction]     [% pts entering induction]
 NOV DAUN     NOV DAUN
Event N = 102 N = 102     N = 55 N = 49
NOV = Novantrone, DAUN = dau