Camptothecin analogues: studies from The Johns Hopkins Oncology Center

William J. Slichenmyer, Eric K. Rowinsky, Louise B. Grochow, Scott H Kaufmann, Ross C. Donehower

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The camptothecin analogues topotecan and irinotecan (CPT-11) are active anticancer drugs. This article reviews the accumulated results of clinical and laboratory studies performed with these agents at The Johns Hopkins Oncology Center. In a phase I clinical and pharmacology trial of topotecan given as a 30-min infusion daily for 5 days every 3 weeks, profound neutropenia precluded dose escalation above 1.5-2.0 mg/m2 per day, the maximum tolerated dose (MTD). The daily ×5 schedule has been developed further with dose escalation using granulocytecolony-stimulating factor support in patients who have kidney or liver dysfunction and given in combination with cisplatin. In addition, a phase I trial of topotecan given as a 5-day continuous intravenous infusion to patients with refractory leukemia has had promising antileukemic responses. A separate series of in vitro studies indicates that a modest degree of resistance to the cytotoxicity of topotecan can be mediated by P-glycoprotein. A phase I and pharmacology study of irinotecan given as a 90-min infusion every 3 weeks has defined an MTD of 240 mg/m2, with dose escalation being limited by several toxicities. These included an acute treatment-related syndrome of flushing, warmth, nausea, vomiting, and diarrhea; a subacute combination of nausea, diarrhea, anorexia, and weight loss; and/or neutropenia. Antitumor activity has been observed with topotecan and irinotecan in patients with a variety of solid tumors and refractory leukemia in our studies, which supports the widespread enthusiasm for this group of compounds.

Original languageEnglish (US)
JournalCancer Chemotherapy and Pharmacology
Volume34
Issue number1 Supplement
DOIs
StatePublished - Jan 1994
Externally publishedYes

Fingerprint

irinotecan
Topotecan
Camptothecin
Oncology
Maximum Tolerated Dose
Neutropenia
Refractory materials
Nausea
Diarrhea
Leukemia
Clinical Trials, Phase I
Clinical Pharmacology
Anorexia
P-Glycoprotein
Cytotoxicity
Intravenous Infusions
Liver
Cisplatin
Vomiting
Toxicity

Keywords

  • Camptothecin
  • Cancer chemotherapy
  • Topoisomerase I

ASJC Scopus subject areas

  • Pharmacology
  • Oncology
  • Cancer Research

Cite this

Camptothecin analogues : studies from The Johns Hopkins Oncology Center. / Slichenmyer, William J.; Rowinsky, Eric K.; Grochow, Louise B.; Kaufmann, Scott H; Donehower, Ross C.

In: Cancer Chemotherapy and Pharmacology, Vol. 34, No. 1 Supplement, 01.1994.

Research output: Contribution to journalArticle

Slichenmyer, William J. ; Rowinsky, Eric K. ; Grochow, Louise B. ; Kaufmann, Scott H ; Donehower, Ross C. / Camptothecin analogues : studies from The Johns Hopkins Oncology Center. In: Cancer Chemotherapy and Pharmacology. 1994 ; Vol. 34, No. 1 Supplement.
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