1%)
Gastrointestinal Disorders
Diarrhea 173 (47%) 23 (6%) 39 (11%) 1 (< 1%)
Nausea 127 (34%) 7 (2%) 85 (23%) 1 (< 1%)
Vomiting 83 (22%) 6 (2%) 38 (10%) 0
Constipation 76 (20%) 4 (1%) 57 (15%) 2 (< 1%)
Abdominal Pain§ 64 (17%) 7 (2%) 23 (6%) 0
Dyspepsia¶ 36 (10%) 0 9 (2%) 0
General Disorders and Administration Site Conditions
Fatigue 136 (37%) 18 (5%) 102 (27%) 11 (3%)
Asthenia 76 (20%) 17 (5%) 46 (12%) 9 (2%)
Pyrexia 45 (12%) 4 (1%) 23 (6%) 1 (< 1%)
Peripheral Edema 34 (9%) 2 (< 1%) 34 (9%) 2 (< 1%)
Mucosal Inflammation 22 (6%) 1 (< 1%) 10 (3%) 1 (< 1%)
Pain 20 (5%) 4 (1%) 18 (5%) 7 (2%)
Infections and Infestations
Urinary Tract Infection# 29 (8%) 6 (2%) 12 (3%) 4 (1%)
Investigations
Weight Decreased 32 (9%) 0 28 (8%) 1 (< 1%)
Metabolism and Nutrition Disorders
Anorexia 59 (16%) 3 (< 1%) 39 (11%) 3 (< 1%)
Dehydration 18 (5%) 8 (2%) 10 (3%) 3 (< 1%)
Musculoskeletal and Connective Tissue Disorders
Back Pain 60 (16%) 14 (4%) 45 (12%) 11 (3%)
Arthralgia 39 (11%) 4 (1%) 31 (8%) 4 (1%)
Muscle Spasms 27 (7%) 0 10 (3%) 0
Nervous System Disorders
Peripheral NeuropathyÞ 50 (13%) 3 (< 1%) 12 (3.2%) 3 (< 1%)
Dysgeusia 41 (11%) 0 15 (4%) 0
Dizziness 30 (8%) 0 21 (6%) 2 (< 1%)
Headache 28 (8%) 0 19 (5%) 0
Renal and Urinary Tract Disorders
Hematuria 62 (17%) 7 (2%) 13 (4%) 1 (< 1%)
Dysuria 25 (7%) 0 5 (1%) 0
Respiratory, Thoracic and Mediastinal Disorders
Dyspnea 43 (12%) 4 (1%) 16 (4%) 2 (< 1%)
Cough 40 (11%) 0 22 (6%) 0
Skin and Subcutaneous Tissue Disorders
Alopecia 37 (10%) 0 18 (5%) 0
Vascular Disorders
Hypotension 20 (5%) 2 (<1 %) 9 (2%) 1 (< 1%)
Median Duration of Treatment 6 cycles
4 cycles
Neutropenia and Associated Clinical Events:
Five patients experienced fatal infectious adverse events (sepsis or septic shock). All had grade 4 neutropenia and one had febrile neutropenia. One additional patient's death was attributed to neutropenia without a documented infection. Twenty-two (6%) patients discontinued JEVTANA treatment due to neutropenia, febrile neutropenia, infection, or sepsis. The most common adverse reaction leading to treatment discontinuation in the JEVTANA group was neutropenia (2%).
Hematuria:
Adverse events of hematuria, including those requiring medical intervention, were more common in JEVTANA-treated patients. The incidence of grade ≥ 2 hematuria was 6% in JEVTANA-treated patients and 2% in mitoxantrone-treated patients. Other factors associated with hematuria were well-balanced between arms and do not account for the increased rate of hematuria on the JEVTANA arm.
Hepatic Laboratory Abnormalities:
The incidences of grade 3–4 increased AST, increased ALT, and increased bilirubin were each ≤ 1%.
Elderly Population:
The following grade 1–4 adverse reactions were reported at rates ≥ 5% higher in patients 65 years of age or greater compared to younger patients: fatigue (40% vs. 30%), neutropenia (97% vs. 89%), asthenia (24% vs. 15%), pyrexia (15% vs. 8%), dizziness (10% vs. 5%), urinary tract infection (10% vs. 3%) and dehydration (7% vs. 2%), respectively.
The incidence of the following grade 3–4 adverse reactions were higher in patients ≥ 65 years of age compared to younger patients; neutropenia (87% vs. 74%), and febrile neutropenia (8% vs. 6%) [see U
