ADVERSE REACTIONS
The table below presents the incidences of adverse reactions derived from an analysis of data contained within literature reports of 7 studies involving 303 pediatric patients in which VUMON was administered by injection as a single agent in a variety of doses and schedules for a variety of hematologic malignancies and solid tumors. The total number of patients evaluable for a given event was not 303 since the individual studies did not address the occurrence of each event listed. Five of these 7 studies assessed VUMON activity in hematologic malignancies, such as leukemia. Thus, many of these patients had abnormal hematologic status at start of therapy with VUMON and were expected to develop significant myelosuppression as an endpoint of treatment.
Single-Agent VUMON Summary of Toxicity for All Evaluable Pediatric Patients | Toxicity | Incidence in
Evaluable Patients
(%) |
|---|
| Hematologic Toxicity | |
| Myelosuppression, nonspecified | 75 |
| Leukopenia (<3,000 WBC/mcL) | 89 |
| Neutropenia (<2,000 ANC/mcL) | 95 |
| Thrombocytopenia (<100,000 plt/mcL) | 85 |
| Anemia | 88 |
| Non-Hematologic Toxicity | |
| Mucositis | 76 |
| Diarrhea | 33 |
| Nausea/vomiting | 29 |
| Infection | 12 |
| Alopecia | 9 |
| Bleeding | 5 |
| Hypersensitivity reactions | 5 |
| Rash | 3 |
| Fever | 3 |
| Hypotension/Cardiovascular | 2 |
| Neurotoxicity | <1 |
| Hepatic dysfunction | <1 |
| Renal dysfunction | <1 |
| Metabolic abnormalities | <1 |
Hematologic Toxicity
VUMON, when used with other chemotherapeutic agents for the treatment of ALL, results in severe myelosuppression. Early onset of profound myelosuppression with delayed recovery can be expected when using the doses and schedules of VUMON necessary for treatment of refractory ALL, since bone marrow hypoplasia is a desired endpoint of therapy. The occurrence of acute non-lymphocytic leukemia (ANLL), with or without a preleukemic phase, has been reported in patients treated with VUMON in combination with other antineoplastic agents. (See PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment of Fertility.)
Gastrointestinal Toxicity
Nausea and vomiting are the most common gastrointestinal toxicities, having occurred in 29% of evaluable pediatric patients. The severity of this nausea and vomiting is generally mild to moderate.
Hypotension
Transient hypotension following rapid intravenous administration has been reported in 2% of evaluable pediatric patients. One episode of sudden death, attributed to probable arrhythmia and intractable hypotension, has been reported in an elderly patient receiving VUMON combination therapy for a non-leukemic malignancy.
No other cardiac toxicity or electrocardiographic changes have been documented. No delayed hypotension has been noted.
Allergic Reactions
Hypersensitivity reactions characterized by chills, fever, tachycardia, flushing, bronchospasm, dyspnea, and blood pressure changes (hypertension or hypotension) have been reported to occur in approximately 5% of evaluable pediatric patients receiving intravenous VUMON. The incidence of hypersensitivity reactions to VUMON appears to be increased in patients with brain tumors and in patients with neuroblastoma.
Central Nervous System
Acute central nervous system depression and hypotension have been observed in patients receiving investigational infusions of high-dose VUMON who were pretreated with antiemetic drugs. The depressant effects of the antiemetic agents and the alcohol content of the VUMON formulation may place patients receiving higher than recommended doses of VUMON at risk for central nervous system depression.
Alopecia
Alopecia, sometimes progressing to total baldness, was observed in 9% of evaluable pediatric patients who received VUMON as single-agent therapy. It was usually reversible.
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