The table below presents the incidencesof adverse reactions derived from an analysis of data contained within literaturereports of 7 studies involving 303 pediatric patients in which VUMON was administeredby injection as a single agent in a variety of doses and schedules for a varietyof hematologic malignancies and solid tumors. The total number of patientseva luable for a given event was not 303 since the individual studies did notaddress the occurrence of each event listed. Five of these 7 studies assessedVUMON activity in hematologic malignancies, such as leukemia. Thus, many ofthese patients had abnormal hematologic status at start of therapy with VUMONand were expected to develop significant myelosuppression as an endpoint oftreatment.

Single-Agent VUMON Summary of Toxicity for All eva luable PediatricPatients Toxicity  Incidence in
eva luablePatients
(%) 
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

VUMON, when used with other chemotherapeutic agents for the treatmentof ALL, results in severe myelosuppression. Early onset of profound myelosuppressionwith delayed recovery can be expected when using the doses and schedules ofVUMON necessary for treatment of refractory ALL, since bone marrow hypoplasiais a desired endpoint of therapy. The occurrence of acute non-lymphocyticleukemia (ANLL), with or without a preleukemic phase, has been reported inpatients treated with VUMON in combination with other antineoplastic agents.(See PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairmentof Fertility .)

Nausea and vomiting are the most common gastrointestinal toxicities,having occurred in 29% of eva luable pediatric patients. The severity of thisnausea and vomiting is generally mild to moderate.

Transient hypotension following rapid intravenous administrationhas been reported in 2% of eva luable pediatric patients. One episode of suddendeath, attributed to probable arrhythmia and intractable hypotension, hasbeen reported in an elderly patient receiving VUMON combination therapy fora non-leukemic malignancy.

No other cardiac toxicity or electrocardiographic changes havebeen documented. No delayed hypotension has been noted.

Hypersensitivity reactions characterized by chills, fever, tachycardia,flushing, bronchospasm, dyspnea, and blood pressure changes (hypertensionor hypotension) have been reported to occur in approximately 5% of eva luablepediatric patients receiving intravenous VUMON. The incidence of hypersensitivityreactions to VUMON appears to be increased in patients with brain tumors andin patients with neuroblastoma.