6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data in Warnings and Precautions reflect exposure to topotecan from 8 trials in which 879 patients with small cell lung cancer (SCLC) and other solid tumors received topotecan 1.5 mg/m2 by intravenous infusion daily for 5 consecutive days, starting on Day 1 of a 21-day cycle.
Small Cell Lung Cancer (SCLC)
The safety of topotecan was evaluated in randomized, comparative trial in patients with recurrent or progressive SCLC (Study 090) [see Clinical Studies (14.1)]. Table 1 shows the Grade 3 or 4 hematologic and non-hematologic adverse reactions in patients with SCLC.
Table 1. Adverse Reactions Occurring in ≥5% of Patients with Small Cell Lung Cancer in Study 090Adverse Reactions | Topotecan (n = 107) | CAV* (n = 104) |
---|
Grade 3–4 (%) | Grade 3–4 (%) |
---|
|
Hematologic |
Grade 4 neutropenia (< 500/mm3) | 70 | 72 |
Grade 3 or 4 anemia (Hgb < 8 g/dL) | 42 | 20 |
Grade 4 thrombocytopenia (< 25,000/mm3) | 29 | 5 |
Febrile neutropenia | 28 | 26 |
Non-Hematologic |
Respiratory, thoracic, and mediastinal | | |
Dyspnea | 9 | 14 |
Pneumonia | 8 | 6 |
General and administrative site conditions | | |
Asthenia | 9 | 7 |
Fatigue | 6 | 10 |
Pain† | 5 | 7 |
Gastrointestinal | | |
Nausea | 8 | 6 |
Abdominal pain | 6 | 4 |
Infections | | |
Sepsis‡ | 5 | 5 |
Hepatobiliary Disorders
Based on 879 patients with small cell lung cancer or another solid tumor who were treated with topotecan, Grade 3 or 4 elevated aspartate (AST) or alanine transaminase (ALT) occurred in 4% and Grade 3 or 4 elevated bilirubin occurred in less than 2% of patients.
6.2 Postmarketing Experience
The following reactions have been identified during postapproval use of topotecan. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatic System
Severe bleeding (in association with thrombocytopenia)
Hypersensitivity
Allergic manifestations, anaphylactoid reactions, angioedema
Gastrointestinal
Abdominal pain potentially associated with neutropenic enterocolitis, gastrointestinal perforation
Pulmonary
Interstitial lung disease
Skin and Subcutaneous Tissue
Severe dermatitis, severe pruritus
General and Administration Site Conditions
Extravasation, mucosal inflammation