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Infusional therapy with alkylating agents

R B Jones1

  • 1University of Colorado Marrow Transplant Program, USA.

The Journal of Infusional Chemotherapy
|January 1, 1996
PubMed
Summary
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Infusing chemotherapy drugs, known as antineoplastics (AA), may offer therapeutic advantages over bolus administration. Future studies will explore AA infusions, considering pharmacokinetic and pharmacodynamic changes for improved cancer treatment.

Area of Science:

  • Pharmacology and Oncology
  • Drug delivery systems in cancer therapy

Background:

  • Historical context of evaluating chemotherapy by infusion, including early phase III studies with etoposide and cisplatin in non-small cell lung cancer.
  • Previous research suggested potential therapeutic index improvements for antineoplastics (AA) using infusional schedules, forming a rationale for their use with bone marrow transplantation (BMT).
  • Concerns were raised regarding the lack of clear pharmacokinetic advantages and potential for increased toxicity with certain infusional schedules, necessitating strong preclinical and pharmacological justification.

Purpose of the Study:

  • To review the rationale and preclinical data supporting the use of infusional antineoplastic (AA) chemotherapy.
  • To highlight the need for scientifically based studies on AA infusions, considering pharmacokinetic (PK) and pharmacodynamic (PD) relationships.
  • To establish a foundation for future research into the benefits and toxicities of prolonged AA administration.

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Main Methods:

  • Review of existing preclinical studies (Teicher, Frei) providing data on the efficacy of infusional AA schedules.
  • Analysis of pharmacokinetic (PK) studies related to AA administration.
  • Consideration of historical clinical trial data and expert commentary (Donehower, Goldberg).

Main Results:

  • Preclinical data suggest that infusional schedules can improve the therapeutic index for most antineoplastics (AA).
  • Early clinical studies showed no advantage for infusional schedules and, in some cases, increased toxicity (e.g., myelotoxicity with cDDP).
  • Pharmacokinetic studies indicated that for drugs with long half-lives, daily infusional doses may not differ significantly from bolus schedules.

Conclusions:

  • A strong scientific rationale, supported by preclinical data and PK/PD understanding, is crucial for designing future studies of AA infusions.
  • Advances in managing toxicities, particularly hematologic toxicity with hematopoietic cell support, enable safer exploration of infusional AA therapy.
  • Future research should focus on understanding the relationship between visceral organ toxicities and PK/PD changes associated with prolonged AA infusion.