Hypersensitivity reactions to teniposide (VM-26): an analysis.

Abstract

An analysis of hypersensitivity reactions to teniposide was approached using three methods: investigator survey, adverse drug reaction analysis, and literature search. By the survey method, hypersensitivity incidence was 6.5% with the majority of the reactions (82%) occurring in brain tumor or neuroblastoma patients. By the second method, 43 cases of hypersensitivity that were reported to the National Cancer Institute (NCI) between January 1983 and October 1985 were analyzed in detail. Reaction onset was unpredictable according to the number of drug doses. The majority of the patients (65%) experiencing the reaction had neuroblastoma or brain tumors, and these patients also tended to react earlier in the course of drug administration than those with hematologic malignancies. Clinical presentation was not correlated with the patient's diagnosis. All patients recovered. However, only six of 13 were successfully rechallenged with the drug. The third approach, the literature search, provided information on 82 hypersensitivity reactions among 2,250 patients (3.6% incidence). Forty-five percent of these reactions were linked to neuroblastoma or brain tumor patients. The analysis of hypersensitivity to teniposide by these three methods provides insight into the true incidence of hypersensitivity reactions in the general patient population. The frequency of the reactions is substantially higher in patients with neuroblastoma and brain tumors. This population should be considered for future trials of aggressive prophylactic therapy.

A Novel Paclitaxel Microemulsion Containing a Reduced Amount of Cremophor EL: Pharmacokinetics, Biodistribution, and In Vivo Antitumor Efficacy and Safety

“…Therefore, in the present study, we chose beagle dogs as an animal model to evaluating the allergic reactions caused by PTX formulations. Due to the amount of CrEL necessary to deliver the required doses of cyclosporine or teniposide being much lower than that in the PTX injection, the reported side effects linked with CrEL are limited [28, 29]. Considering the formulation of the present PTX microemulsion, the amount of CrEL was markedly reduced compared with that in the PTX injection (0.8 g in microemulsion versus 2.6 g in injection).…”

Pulmonary Complications of Novel Antineoplastic Agents for Solid Tumors

“…However, the timing of the hypersensitivity reaction is unpredictable and may occur during the first treatment cycle or during subsequent treatment cycles. 68…”

Toxicity studies of cremophor-free paclitaxel solid dispersion formulated by a supercritical antisolvent process

“…However the ethanol/Cremophor EL vehicle required to solubilize the paclitaxel in Taxol ® is toxic. Although it has been used to administer other drugs, such as cyclosporine (Howrie et al, 1985) and teniposide (O'Dwyer et al, 1986), the amount of Cremophor EL necessary to deliver the required doses of Taxol ® is significantly higher than that administered with any other marketed drug (Rowinsky et al, 1992). Thus the vehicle has been shown to cause serious, even fatal, hypersensitivity episodes (Dye and Watkins, 1980) at all steps in both preclinical and clinical testing (Weiss et al, 1990).…”