Dose-dependent effect of thalidomide on overall survival in relapsed multiple myeloma

Clin Cancer Res. 2002 Nov;8(11):3377-82.

Abstract

Purpose: Although thalidomide (Thal) was introduced successfully in the treatment of multiple myeloma (MM), the optimal Thal dosage and schedule are still controversial. The aim of this study was to analyze whether the effect of Thal in MM is dose dependent and whether the outcome might be improved when the Thal dosage is adjusted to parameters reflecting body size.

Experimental design: From December 1998 to March 2001, 83 patients with relapsed MM were enrolled in a clinical Phase II trial and treated with a maximum Thal dosage of 400 mg daily. We performed a retrospective analysis and studied the effect of the cumulative 3-month Thal dosage on progression-free survival and overall survival (OS) together with age and the pretreatment levels of beta2-microglobulin, C-reactive protein, albumin, and hemoglobin in a Cox regression model.

Results: After a median follow-up time of 17 months (range, 1-30 months), the estimated 12-month progression-free survival and OS were 45% (SE = 6%) and 86% (SE = 4%) for the whole patient group. After backward selection, hemoglobin (P = 0.002) and the cumulative 3-month Thal dosage (P = 0.002) were the remaining factors for OS. The effect on OS could not be improved when the cumulative 3-month Thal dosage was adjusted to parameters reflecting body size such as height, weight, body surface area, or body mass index in comparison with Thal alone.

Conclusions: Our retrospective analysis demonstrates that the cumulative 3-month Thal dosage is one of the major prognostic factors for OS, supporting the hypothesis of a dose-dependent effect of Thal in relapsed MM.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Albumins / biosynthesis
  • Body Height
  • Body Weight
  • C-Reactive Protein / biosynthesis
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Female
  • Hemoglobins / biosynthesis
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality
  • Multiple Myeloma / pathology*
  • Prognosis
  • Proportional Hazards Models
  • Recurrence
  • Retrospective Studies
  • Thalidomide / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • beta 2-Microglobulin / blood

Substances

  • Albumins
  • Hemoglobins
  • Immunosuppressive Agents
  • beta 2-Microglobulin
  • Thalidomide
  • C-Reactive Protein