Phase i trial of autologous hematopoietic SCT with escalating doses of topotecan combined with CY and carboplatin in patients with relapsed or persistent ovarian or primary peritoneal carcinoma

M. R. Litzow; P. P. Peethambaram; S. L. Safgren; G. L. Keeney; S. M. Ansell; A. Dispenzieri; M. A. Elliott; D. A. Gastineau; M. A. Gertz; D. J. Inwards; M. Q. Lacy; I. N.M. Micallef; L. F. Porrata; W. L. Lingle; L. C. Hartmann; M. H. Frost; B. A. Barrette; H. J. Long; V. J. Suman; J. M. Reid; M. M. Ames; S. H. Kaufmann

doi:10.1038/bmt.2009.181

Phase i trial of autologous hematopoietic SCT with escalating doses of topotecan combined with CY and carboplatin in patients with relapsed or persistent ovarian or primary peritoneal carcinoma

M. R. Litzow, P. P. Peethambaram, S. L. Safgren, G. L. Keeney, S. M. Ansell, A. Dispenzieri, M. A. Elliott, D. A. Gastineau, M. A. Gertz, D. J. Inwards, M. Q. Lacy, I. N.M. Micallef, L. F. Porrata, W. L. Lingle, L. C. Hartmann, M. H. Frost, B. A. Barrette, H. J. Long, V. J. Suman, J. M. ReidM. M. Ames, S. H. Kaufmann

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5 Scopus citations

Abstract

We designed a phase I clinical trial of escalating doses of topotecan with CY and carboplatin in combination with autologous hematopoietic SCT (AHSCT) for the treatment of relapsed or persistent platinum sensitive ovarian or primary peritoneal carcinoma. After stem cell collection, 16 patients received topotecan at 1.5, 2.5, 3.5, 4.5 or 6.0mgm²d combined with CY 1.5gm ²d and carboplatin 200mgm²d, all by 4-day continuous infusion. Steady state pharmacokinetics of topotecan and carboplatin were examined. Pre-treatment biopsies were examined for the expression of topoisomerase (topo) I, Ki67 and Bcl-2 family members by immunohistochemistry. One of six patients at a topotecan dose of 4.5mgm²d and two of three patients at 6.0mgm²d had dose-limiting toxicity of grade 3 stomatitis lasting >2 weeks. There was no treatment-related mortality. As topotecan clearance was constant over the dose range examined, topotecan steady state plasma concentrations increased with dose. Median progression-free survival and overall survival were 6.5 months and 2.7 years, respectively. Shorter progression-free survival was observed in tumors with low topo expression (P0.04). Topotecan can safely be dose escalated to 4.5mgm²d in combination with CY, carboplatin and AHSCT. This trial is registered at ClinicalTrials.gov as NCT00652691.

Original language	English (US)
Pages (from-to)	490-497
Number of pages	8
Journal	Bone Marrow Transplantation
Volume	45
Issue number	3
DOIs	https://doi.org/10.1038/bmt.2009.181
State	Published - 2010

Keywords

Autologous hematopoietic stem cell transplantation
Phase I
Topotecan

ASJC Scopus subject areas

Hematology
Transplantation

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10.1038/bmt.2009.181

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Litzow, M. R., Peethambaram, P. P., Safgren, S. L., Keeney, G. L., Ansell, S. M., Dispenzieri, A., Elliott, M. A., Gastineau, D. A., Gertz, M. A., Inwards, D. J., Lacy, M. Q., Micallef, I. N. M., Porrata, L. F., Lingle, W. L., Hartmann, L. C., Frost, M. H., Barrette, B. A., Long, H. J., Suman, V. J., ... Kaufmann, S. H. (2010). Phase i trial of autologous hematopoietic SCT with escalating doses of topotecan combined with CY and carboplatin in patients with relapsed or persistent ovarian or primary peritoneal carcinoma. Bone Marrow Transplantation, 45(3), 490-497. https://doi.org/10.1038/bmt.2009.181

Phase i trial of autologous hematopoietic SCT with escalating doses of topotecan combined with CY and carboplatin in patients with relapsed or persistent ovarian or primary peritoneal carcinoma. / Litzow, M. R.; Peethambaram, P. P.; Safgren, S. L. et al.
In: Bone Marrow Transplantation, Vol. 45, No. 3, 2010, p. 490-497.

Research output: Contribution to journal › Article › peer-review

Litzow, MR, Peethambaram, PP, Safgren, SL, Keeney, GL , Ansell, SM , Dispenzieri, A, Elliott, MA, Gastineau, DA, Gertz, MA, Inwards, DJ, Lacy, MQ , Micallef, INM, Porrata, LF, Lingle, WL, Hartmann, LC, Frost, MH, Barrette, BA, Long, HJ, Suman, VJ , Reid, JM, Ames, MM & Kaufmann, SH 2010, 'Phase i trial of autologous hematopoietic SCT with escalating doses of topotecan combined with CY and carboplatin in patients with relapsed or persistent ovarian or primary peritoneal carcinoma', Bone Marrow Transplantation, vol. 45, no. 3, pp. 490-497. https://doi.org/10.1038/bmt.2009.181

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title = "Phase i trial of autologous hematopoietic SCT with escalating doses of topotecan combined with CY and carboplatin in patients with relapsed or persistent ovarian or primary peritoneal carcinoma",

abstract = "We designed a phase I clinical trial of escalating doses of topotecan with CY and carboplatin in combination with autologous hematopoietic SCT (AHSCT) for the treatment of relapsed or persistent platinum sensitive ovarian or primary peritoneal carcinoma. After stem cell collection, 16 patients received topotecan at 1.5, 2.5, 3.5, 4.5 or 6.0mgm2d combined with CY 1.5gm 2d and carboplatin 200mgm2d, all by 4-day continuous infusion. Steady state pharmacokinetics of topotecan and carboplatin were examined. Pre-treatment biopsies were examined for the expression of topoisomerase (topo) I, Ki67 and Bcl-2 family members by immunohistochemistry. One of six patients at a topotecan dose of 4.5mgm2d and two of three patients at 6.0mgm2d had dose-limiting toxicity of grade 3 stomatitis lasting >2 weeks. There was no treatment-related mortality. As topotecan clearance was constant over the dose range examined, topotecan steady state plasma concentrations increased with dose. Median progression-free survival and overall survival were 6.5 months and 2.7 years, respectively. Shorter progression-free survival was observed in tumors with low topo expression (P0.04). Topotecan can safely be dose escalated to 4.5mgm2d in combination with CY, carboplatin and AHSCT. This trial is registered at ClinicalTrials.gov as NCT00652691.",

keywords = "Autologous hematopoietic stem cell transplantation, Phase I, Topotecan",

author = "Litzow, {M. R.} and Peethambaram, {P. P.} and Safgren, {S. L.} and Keeney, {G. L.} and Ansell, {S. M.} and A. Dispenzieri and Elliott, {M. A.} and Gastineau, {D. A.} and Gertz, {M. A.} and Inwards, {D. J.} and Lacy, {M. Q.} and Micallef, {I. N.M.} and Porrata, {L. F.} and Lingle, {W. L.} and Hartmann, {L. C.} and Frost, {M. H.} and Barrette, {B. A.} and Long, {H. J.} and Suman, {V. J.} and Reid, {J. M.} and Ames, {M. M.} and Kaufmann, {S. H.}",

note = "Funding Information: We thank the Mayo Clinic Tissue and Cell Molecular Analysis Shared Resources for assistance with the immunohistochemical analyses of biopsy samples and gratefully acknowledge the contributions of Margo Marzolf for data support, Kim Kalli for sample acquisition and Denise Chase for manuscript preparation. M. Litzow received research funding support from GlaxoSmithKline to conduct this research: Glaxo SmithKline, R01 CA73709, P30 CA15083.",

year = "2010",

doi = "10.1038/bmt.2009.181",

language = "English (US)",

volume = "45",

pages = "490--497",

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AU - Peethambaram, P. P.

AU - Safgren, S. L.

AU - Keeney, G. L.

AU - Ansell, S. M.

AU - Dispenzieri, A.

AU - Elliott, M. A.

AU - Gastineau, D. A.

AU - Gertz, M. A.

AU - Inwards, D. J.

AU - Lacy, M. Q.

AU - Micallef, I. N.M.

AU - Porrata, L. F.

AU - Lingle, W. L.

AU - Hartmann, L. C.

AU - Frost, M. H.

AU - Barrette, B. A.

AU - Long, H. J.

AU - Suman, V. J.

AU - Reid, J. M.

AU - Ames, M. M.

AU - Kaufmann, S. H.

N1 - Funding Information: We thank the Mayo Clinic Tissue and Cell Molecular Analysis Shared Resources for assistance with the immunohistochemical analyses of biopsy samples and gratefully acknowledge the contributions of Margo Marzolf for data support, Kim Kalli for sample acquisition and Denise Chase for manuscript preparation. M. Litzow received research funding support from GlaxoSmithKline to conduct this research: Glaxo SmithKline, R01 CA73709, P30 CA15083.

PY - 2010

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N2 - We designed a phase I clinical trial of escalating doses of topotecan with CY and carboplatin in combination with autologous hematopoietic SCT (AHSCT) for the treatment of relapsed or persistent platinum sensitive ovarian or primary peritoneal carcinoma. After stem cell collection, 16 patients received topotecan at 1.5, 2.5, 3.5, 4.5 or 6.0mgm2d combined with CY 1.5gm 2d and carboplatin 200mgm2d, all by 4-day continuous infusion. Steady state pharmacokinetics of topotecan and carboplatin were examined. Pre-treatment biopsies were examined for the expression of topoisomerase (topo) I, Ki67 and Bcl-2 family members by immunohistochemistry. One of six patients at a topotecan dose of 4.5mgm2d and two of three patients at 6.0mgm2d had dose-limiting toxicity of grade 3 stomatitis lasting >2 weeks. There was no treatment-related mortality. As topotecan clearance was constant over the dose range examined, topotecan steady state plasma concentrations increased with dose. Median progression-free survival and overall survival were 6.5 months and 2.7 years, respectively. Shorter progression-free survival was observed in tumors with low topo expression (P0.04). Topotecan can safely be dose escalated to 4.5mgm2d in combination with CY, carboplatin and AHSCT. This trial is registered at ClinicalTrials.gov as NCT00652691.

AB - We designed a phase I clinical trial of escalating doses of topotecan with CY and carboplatin in combination with autologous hematopoietic SCT (AHSCT) for the treatment of relapsed or persistent platinum sensitive ovarian or primary peritoneal carcinoma. After stem cell collection, 16 patients received topotecan at 1.5, 2.5, 3.5, 4.5 or 6.0mgm2d combined with CY 1.5gm 2d and carboplatin 200mgm2d, all by 4-day continuous infusion. Steady state pharmacokinetics of topotecan and carboplatin were examined. Pre-treatment biopsies were examined for the expression of topoisomerase (topo) I, Ki67 and Bcl-2 family members by immunohistochemistry. One of six patients at a topotecan dose of 4.5mgm2d and two of three patients at 6.0mgm2d had dose-limiting toxicity of grade 3 stomatitis lasting >2 weeks. There was no treatment-related mortality. As topotecan clearance was constant over the dose range examined, topotecan steady state plasma concentrations increased with dose. Median progression-free survival and overall survival were 6.5 months and 2.7 years, respectively. Shorter progression-free survival was observed in tumors with low topo expression (P0.04). Topotecan can safely be dose escalated to 4.5mgm2d in combination with CY, carboplatin and AHSCT. This trial is registered at ClinicalTrials.gov as NCT00652691.

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Phase i trial of autologous hematopoietic SCT with escalating doses of topotecan combined with CY and carboplatin in patients with relapsed or persistent ovarian or primary peritoneal carcinoma

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Keywords

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