Unexpected toxicity associated with use of body surface area for dosing melphalan in the dog.

Journal Article (Journal Article)

A multiinstitutional Phase I study using i.v. melphalan was conducted in dogs with spontaneously occurring neoplasia. Melphalan was administered at 7.5, 10, 11.25, 12.5, and 20 mg/m2 of body surface area. Disproportionately greater toxicity was observed in small dogs. Seven of the eight dogs (88%) weighing less than 14 kg experienced severe myelosuppression (neutropenia, less than 1500/mm3; and/or thrombocytopenia, less than 80,000/mm3), whereas only three of 13 dogs (23%) weighing greater than 14 kg developed severe myelosuppression (P = 0.016). We concluded that small dogs are at greater risk of developing bone marrow toxicity from i.v. melphalan than large dogs if body surface area is used to calculate the dose. Although both body surface area and weight were found to be significantly correlated with severity of toxicity, melphalan-induced toxicity in dogs can be more accurately estimated by body weight than by surface area, P = 0.008 versus P = 0.022, respectively. It may be necessary to prescribe antineoplastic agents that are eliminated by processes not primarily under metabolic influence or that produce side effects on tissue not correlated to basal metabolic rate on a parameter other than body surface area. In dogs, melphalan should be dosed on a weight basis, and treatment groups should be stratified by weight in randomized clinical studies, particularly when the weight range of treated subjects is great.

Full Text

Duke Authors

Cited Authors

  • Page, RL; Macy, DW; Thrall, DE; Dewhirst, MW; Allen, SL; Heidner, GL; Sim, DA; McGee, ML; Gillette, EL

Published Date

  • January 15, 1988

Published In

Volume / Issue

  • 48 / 2

Start / End Page

  • 288 - 290

PubMed ID

  • 3335006

International Standard Serial Number (ISSN)

  • 0008-5472


  • eng

Conference Location

  • United States