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 6.0 mg/m(2)/d combined with CY 1.5 g/m(2)/d and carboplatin 200 mg/m(2)/d, 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 4.5 mg/m(2)/d and two of three patients at 6.0 mg/m(2)/d 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 (P=0.04). Topotecan can safely be dose escalated to 4.5 mg/m(2)/d in combination with CY, carboplatin and AHSCT. This trial is registered at ClinicalTrials.gov as NCT00652691.

journal_name

Bone Marrow Transplant

authors

Litzow MR,Peethambaram PP,Safgren SL,Keeney GL,Ansell SM,Dispenzieri A,Elliott MA,Gastineau DA,Gertz MA,Inwards DJ,Lacy MQ,Micallef IN,Porrata LF,Lingle WL,Hartmann LC,Frost MH,Barrette BA,Long HJ,Suman VJ,Reid JM,

doi

10.1038/bmt.2009.181

subject

Has Abstract

pub_date

2010-03-01 00:00:00

pages

490-7

issue

3

eissn

0268-3369

issn

1476-5365

pii

bmt2009181

journal_volume

45

pub_type

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