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Vumon

Brand Name:	Vumon	Trade Name:	teniposide, VM-26
FDA Approved For:	VUMON, in combination with other approved anticancer agents, is indicated for induction therapy in patients with refractory childhood acute lymphoblastic leukemia.	Pediatric Use:	?
Carcinogen:	Children at SJCRH with ALL in remission who received maintenance therapy with VUMON at weekly or twice weekly doses (plus other chemotherapeutic agents), had a relative risk of developing secondary acute nonlymphocytic leukemia (ANLL) approximately 12 times that of patients treated according to other less intensive schedules. 6 A short course of VUMON for remission-induction and/or consolidation therapy was not associated with an increased risk of secondary ANLL, but the number of patients assessed was small. The potential benefit from VUMON must be weighed on a case by case basis against the potential risk of the induction of a secondary leukemia. The carcinogenicity of teniposide has not been studied in laboratory animals. Compounds with similar mechanisms of action and mutagenicity profiles have been reported to be carcinogenic and teniposide should be considered a potential carcinogen in humans.	Mutagen:	Teniposide has been shown to be mutagenic in various bacterial and mammalian genetic toxicity tests. These include positive mutagenic effects in the Ames/Salmonella and B. subtilis bacterial mutagenicity assays. Teniposide caused gene mutations in both Chinese hamster ovary cells and mouse lymphoma cells and DNA damage as measured by alkaline elution in human lung carcinoma derived cell lines. In addition, teniposide induced aberrations in chromosome structure in primary cultures of human lymphocytes in vitro and in L5178y/TK +/- mouse lymphoma cells in vitro . Chromosome aberrations were observed in vivo in the embryonic tissue of pregnant Swiss albino mice treated with teniposide. Teniposide also caused a dose-related increase in sister chromatid exchanges in Chinese hamster ovary cells and it has been shown to be embryotoxic and teratogenic in rats receiving teniposide during organogenesis.
Manufacturer and/or Distributor:	Bristol-Myers Squibb

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 seven 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. (See Table) 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 percent 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 percent 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 percent 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. 1 Central Nervous System: Acute central nervous system depression and hypotension have been observed in patients receiving investigational infusions of high-dose VUMON (teniposide injection) 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 percent of evaluable pediatric patients who received VUMON as single agent therapy. It was usually reversible. )

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