Phase 1 study of XL119, a rebeccamycin analog, in patients with refractory hematologic malignancies

Gautam Borthakur, Yesid Alvarado, Farhad Ravandi-Kashani, Jorge Cortes, Zeev Estrov, Stefan Faderl, Percy Ivy, Carlos Bueso-Ramos, B. Nebiyou Bekele, Francis Giles

Research output: Contribution to journalArticle

Abstract

BACKGROUND. XL119 is a water-soluble derivative of rebeccamycin with dose-dependent myelosuppression as dose-limiting toxicity in phase 1 studies of solid tumors. A phase 1 study was conducted to determine the maximum tolerated dose and toxicities of XL119 in patients with advanced myelodysplastic syndrome and relapsed or refractory acute leukemias. METHODS. Thirty-one patients were treated at 7 dose levels ranging from 140 to 260 mg/m2/daily times 5 in a 21-day cycle. Consenting patients had correlative biologic parameters studied. RESULTS. Dose-limiting toxicity was grade 3/4 mucositis. The recommended phase 2 dose in hematologic malignancies is 240 mg/m 2/daily times 5 in a 21-day cycle. Clinically significant reduction in bone marrow blasts were seen in 5 patients and additional patients had reductions in peripheral blood blasts. However, the responses were transient. Changes of plasma vascular endothelial growth factor levels from Day 1 to Day 7 correlated negatively with changes in peripheral blood blasts from Day 1 to Day 7. CONCLUSIONS. Further assessment of XL119 in combination with other agents in patients with acute leukemias and high-risk myelodysplastic syndrome is warranted.

Original languageEnglish (US)
Pages (from-to)360-366
Number of pages7
JournalCancer
Volume113
Issue number2
DOIs
StatePublished - Jul 15 2008
Externally publishedYes

Fingerprint

Hematologic Neoplasms
Myelodysplastic Syndromes
Leukemia
Mucositis
Maximum Tolerated Dose
Proxy
Vascular Endothelial Growth Factor A
Bone Marrow
rebeccamycin
Water
Neoplasms

Keywords

  • Leukemia
  • Phase 1
  • Rebeccamycin analog
  • XL119

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Borthakur, G., Alvarado, Y., Ravandi-Kashani, F., Cortes, J., Estrov, Z., Faderl, S., ... Giles, F. (2008). Phase 1 study of XL119, a rebeccamycin analog, in patients with refractory hematologic malignancies. Cancer, 113(2), 360-366. https://doi.org/10.1002/cncr.23559

Phase 1 study of XL119, a rebeccamycin analog, in patients with refractory hematologic malignancies. / Borthakur, Gautam; Alvarado, Yesid; Ravandi-Kashani, Farhad; Cortes, Jorge; Estrov, Zeev; Faderl, Stefan; Ivy, Percy; Bueso-Ramos, Carlos; Bekele, B. Nebiyou; Giles, Francis.

In: Cancer, Vol. 113, No. 2, 15.07.2008, p. 360-366.

Research output: Contribution to journalArticle

Borthakur, G, Alvarado, Y, Ravandi-Kashani, F, Cortes, J, Estrov, Z, Faderl, S, Ivy, P, Bueso-Ramos, C, Bekele, BN & Giles, F 2008, 'Phase 1 study of XL119, a rebeccamycin analog, in patients with refractory hematologic malignancies', Cancer, vol. 113, no. 2, pp. 360-366. https://doi.org/10.1002/cncr.23559
Borthakur G, Alvarado Y, Ravandi-Kashani F, Cortes J, Estrov Z, Faderl S et al. Phase 1 study of XL119, a rebeccamycin analog, in patients with refractory hematologic malignancies. Cancer. 2008 Jul 15;113(2):360-366. https://doi.org/10.1002/cncr.23559
Borthakur, Gautam ; Alvarado, Yesid ; Ravandi-Kashani, Farhad ; Cortes, Jorge ; Estrov, Zeev ; Faderl, Stefan ; Ivy, Percy ; Bueso-Ramos, Carlos ; Bekele, B. Nebiyou ; Giles, Francis. / Phase 1 study of XL119, a rebeccamycin analog, in patients with refractory hematologic malignancies. In: Cancer. 2008 ; Vol. 113, No. 2. pp. 360-366.
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