A phase I study of liposomal doxorubicin (Doxil) with topotecan

Christopher Ryan, Gini F. Fleming, Linda Janisch, Mark J. Ratain

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

New therapies are needed for patients with advanced ovarian cancer who relapse after initial treatment with platinum and/or paclitaxel-based regimens. This study sought to determine the toxicities of combined liposomal doxorubicin (Doxil) and topotecan, and to determine a regimen for future phase II testing in ovarian cancer. Nine patients with advanced malignancies were treated with topotecan 1.0 mg/m2/day × 5 days followed by liposomal doxorubicin at a starting dose of 30 mg/m2 on day 5. Cycles were repeated every 28 days. A total of 13 cycles of therapy were administered. Grade IV neutropenia and grade IV thrombocytopenia developed in both of the two patients treated at the first dose level. Subsequent patients received only 20 mg/m2 liposomal doxorubicin. At that dose level, three patients experienced dose-limiting toxicity (one grade IV neutropenia, two grade IV neutropenia and thrombocytopenia). No responses were observed. These data indicate that the described regimen of liposomal doxorubicin and topotecan is not feasible because of excessive hematologic toxicity. Escalation to doses of liposomal doxorubicin or topotecan that have previously demonstrated antitumor activity was not possible. Future strategies to minimize such toxicity may include limiting eligibility to patients with minimal prior therapy, reducing the number of days of topotecan administration, or use of oral topotecan.

Original languageEnglish (US)
Pages (from-to)297-300
Number of pages4
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume23
Issue number3
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Topotecan
Neutropenia
Thrombocytopenia
Ovarian Neoplasms
Therapeutics
Paclitaxel
Platinum
liposomal doxorubicin
Recurrence
Neoplasms

Keywords

  • Clinical trials
  • Doxorubicin
  • Ovarian neoplasms
  • Phase I
  • Topotecan

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A phase I study of liposomal doxorubicin (Doxil) with topotecan. / Ryan, Christopher; Fleming, Gini F.; Janisch, Linda; Ratain, Mark J.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 23, No. 3, 2000, p. 297-300.

Research output: Contribution to journalArticle

Ryan, Christopher ; Fleming, Gini F. ; Janisch, Linda ; Ratain, Mark J. / A phase I study of liposomal doxorubicin (Doxil) with topotecan. In: American Journal of Clinical Oncology: Cancer Clinical Trials. 2000 ; Vol. 23, No. 3. pp. 297-300.
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