Phase I study of pegylated liposomal doxorubicin and gemcitabine in patients with advanced malignancies

Paula M. Fracasso, Kristie A. Blum, Benjamin R. Tan, Carole L. Fears, Nancy L. Bartlett, Matthew A. Arquette, Romnee Clark

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

BACKGROUND. Pegylated liposomal doxorubicin (PEG-LD) and gemcitabine have single-agent activity in breast and ovarian carcinoma patients. We conducted a Phase I trial to evaluate the maximum tolerated dose (MTD) and toxicities of this combination in patients with advanced malignancies. METHODS. Twenty-six patients with refractory or recurrent malignancies were enrolled in this dose escalation trial. Dose escalation proceeded from a starting level of PEG-LD 20 mg/m2 and gemcitabine 1000 mg/m2 administered on Days 1 and 15 of a 28-day cycle. RESULTS. The MTD was PEG-LD 20 mg/m2 and gemcitabine 2000 mg/m2 administered on Days 1 and 15 of a 28-day cycle. Dose-limiting toxicity, a Grade 3 rash, was observed in one patient during Cycle 1 and Grade 3 stomatitis and a rash were observed in a second patient during Cycle 2 after administration of PEG-LD 25 mg/m2 and gemcitabine 2000 mg/m2. Other side effects included palmar-plantar erythrodysesthesia, nausea, and fatigue. One complete and two partial responses were observed. CONCLUSIONS. The recommended Phase II dose is PEG-LD 20 mg/m2 with gemcitabine 2000 mg/m2 on Days 1 and 15 of a 28-day cycle. A trial with this combination is currently ongoing at this institution comprising patients with refractory ovarian carcinoma.

Original languageEnglish (US)
Pages (from-to)2223-2229
Number of pages7
JournalCancer
Volume95
Issue number10
DOIs
StatePublished - Nov 15 2002
Externally publishedYes

Fingerprint

gemcitabine
Neoplasms
Maximum Tolerated Dose
Exanthema
Stomatitis
Nausea
Fatigue
liposomal doxorubicin
Breast Neoplasms
Carcinoma

Keywords

  • Doxil®
  • Gemcitabine
  • Gemzar®
  • Palmar-plantar erythrodysesthesia
  • Pegylated liposomal doxorubicin
  • Phase I

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Fracasso, P. M., Blum, K. A., Tan, B. R., Fears, C. L., Bartlett, N. L., Arquette, M. A., & Clark, R. (2002). Phase I study of pegylated liposomal doxorubicin and gemcitabine in patients with advanced malignancies. Cancer, 95(10), 2223-2229. https://doi.org/10.1002/cncr.10937

Phase I study of pegylated liposomal doxorubicin and gemcitabine in patients with advanced malignancies. / Fracasso, Paula M.; Blum, Kristie A.; Tan, Benjamin R.; Fears, Carole L.; Bartlett, Nancy L.; Arquette, Matthew A.; Clark, Romnee.

In: Cancer, Vol. 95, No. 10, 15.11.2002, p. 2223-2229.

Research output: Contribution to journalArticle

Fracasso, PM, Blum, KA, Tan, BR, Fears, CL, Bartlett, NL, Arquette, MA & Clark, R 2002, 'Phase I study of pegylated liposomal doxorubicin and gemcitabine in patients with advanced malignancies', Cancer, vol. 95, no. 10, pp. 2223-2229. https://doi.org/10.1002/cncr.10937
Fracasso PM, Blum KA, Tan BR, Fears CL, Bartlett NL, Arquette MA et al. Phase I study of pegylated liposomal doxorubicin and gemcitabine in patients with advanced malignancies. Cancer. 2002 Nov 15;95(10):2223-2229. https://doi.org/10.1002/cncr.10937
Fracasso, Paula M. ; Blum, Kristie A. ; Tan, Benjamin R. ; Fears, Carole L. ; Bartlett, Nancy L. ; Arquette, Matthew A. ; Clark, Romnee. / Phase I study of pegylated liposomal doxorubicin and gemcitabine in patients with advanced malignancies. In: Cancer. 2002 ; Vol. 95, No. 10. pp. 2223-2229.
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AB - BACKGROUND. Pegylated liposomal doxorubicin (PEG-LD) and gemcitabine have single-agent activity in breast and ovarian carcinoma patients. We conducted a Phase I trial to evaluate the maximum tolerated dose (MTD) and toxicities of this combination in patients with advanced malignancies. METHODS. Twenty-six patients with refractory or recurrent malignancies were enrolled in this dose escalation trial. Dose escalation proceeded from a starting level of PEG-LD 20 mg/m2 and gemcitabine 1000 mg/m2 administered on Days 1 and 15 of a 28-day cycle. RESULTS. The MTD was PEG-LD 20 mg/m2 and gemcitabine 2000 mg/m2 administered on Days 1 and 15 of a 28-day cycle. Dose-limiting toxicity, a Grade 3 rash, was observed in one patient during Cycle 1 and Grade 3 stomatitis and a rash were observed in a second patient during Cycle 2 after administration of PEG-LD 25 mg/m2 and gemcitabine 2000 mg/m2. Other side effects included palmar-plantar erythrodysesthesia, nausea, and fatigue. One complete and two partial responses were observed. CONCLUSIONS. The recommended Phase II dose is PEG-LD 20 mg/m2 with gemcitabine 2000 mg/m2 on Days 1 and 15 of a 28-day cycle. A trial with this combination is currently ongoing at this institution comprising patients with refractory ovarian carcinoma.

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