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Sequential topotecan and oral etoposide in recurrent ovarian carcinoma pretreated with platinum-taxane - Results from a multicenter phase I/II study

Gronlund, B; Engelholm, SA; Horvath, G; Maenpaa, J and Ridderheim, Mona LU (2005) In Cancer 103(7). p.1388-1396
Abstract
BACKGROUND. The objectives of this study were to determine the maximum tolerable dose (MTD), toxicity, efficacy, and feasibility of a sequential regimen of fixed-dose topotecan (1.00 mg/m(2) on Days 1-5) and increasing doses of oral etoposide (50 mg, 75 mg, and 100 mg on Days 6-12 or Days 6-19) in patients with recurrent ovarian carcinoma. METHODS. This multicenter, open-label study was planned as a Phase I-II study that included patients with epithelial ovarian carcinoma who failed or who developed recurrent disease < 12 months after the end of platinum and taxane-containing chemotherapy. Dose-limiting toxicity (DLT) was defined as follows: Grade 4 neutropenia for > 1 week, or neutropenic fever 38.5 degrees C for > 24... (More)
BACKGROUND. The objectives of this study were to determine the maximum tolerable dose (MTD), toxicity, efficacy, and feasibility of a sequential regimen of fixed-dose topotecan (1.00 mg/m(2) on Days 1-5) and increasing doses of oral etoposide (50 mg, 75 mg, and 100 mg on Days 6-12 or Days 6-19) in patients with recurrent ovarian carcinoma. METHODS. This multicenter, open-label study was planned as a Phase I-II study that included patients with epithelial ovarian carcinoma who failed or who developed recurrent disease < 12 months after the end of platinum and taxane-containing chemotherapy. Dose-limiting toxicity (DLT) was defined as follows: Grade 4 neutropenia for > 1 week, or neutropenic fever 38.5 degrees C for > 24 hours/sepsis, or Grade 4 thrombocytopenia for > 1 week, or thrombocytopenia with bleeding, or Grade 3-4 nonhematologic toxicity. RESULTS. The MTD, as defined in the protocol, could not be settled because of unpredictable toxicity, because DLT was found at all dose levels except the starting dose level. In 28 patients (Phase I), 155 cycles were evaluable for toxicity. The main DLT was neutropenia Grade 4 for > 1 week or neutropenic fever/sepsis. Overall, neutropenia Grade 4 that lasted > 1 week and sepsis were noticed in 3% and 2% of cycles, respectively. Because no MTD was reached, the planned Phase II trial was not initiated. However, the patients from Phase I were followed until they developed progressive disease and, among them, 9 patients (32%) obtained an objective response (according to Response Evaluation Criteria in Solid Tumors (RECIST) or CA125 response criteria). CONCLUSIONS. Combined topotecan and oral etoposide was inappropriate in patients with recurrent ovarian carcinoma because of unpredictable hematologic toxicity. However, the high objective response rate highlighted the potential additive effect of topoisomerase I and II inhibitors. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
topoisomerase inhibitor, etoposide, topotecan, chemotherapy, second-line treatment, ovarian neoplasms, recurrence, Phase 1, response
in
Cancer
volume
103
issue
7
pages
1388 - 1396
publisher
John Wiley & Sons
external identifiers
  • pmid:15719439
  • wos:000227770400010
  • scopus:15744403993
ISSN
1097-0142
DOI
10.1002/cncr.20921
language
English
LU publication?
yes
id
d32dec31-cc6c-4859-b89f-f5474544bfcd (old id 248030)
date added to LUP
2007-08-24 13:33:07
date last changed
2017-01-01 04:57:02
@article{d32dec31-cc6c-4859-b89f-f5474544bfcd,
  abstract     = {BACKGROUND. The objectives of this study were to determine the maximum tolerable dose (MTD), toxicity, efficacy, and feasibility of a sequential regimen of fixed-dose topotecan (1.00 mg/m(2) on Days 1-5) and increasing doses of oral etoposide (50 mg, 75 mg, and 100 mg on Days 6-12 or Days 6-19) in patients with recurrent ovarian carcinoma. METHODS. This multicenter, open-label study was planned as a Phase I-II study that included patients with epithelial ovarian carcinoma who failed or who developed recurrent disease &lt; 12 months after the end of platinum and taxane-containing chemotherapy. Dose-limiting toxicity (DLT) was defined as follows: Grade 4 neutropenia for &gt; 1 week, or neutropenic fever 38.5 degrees C for &gt; 24 hours/sepsis, or Grade 4 thrombocytopenia for &gt; 1 week, or thrombocytopenia with bleeding, or Grade 3-4 nonhematologic toxicity. RESULTS. The MTD, as defined in the protocol, could not be settled because of unpredictable toxicity, because DLT was found at all dose levels except the starting dose level. In 28 patients (Phase I), 155 cycles were evaluable for toxicity. The main DLT was neutropenia Grade 4 for &gt; 1 week or neutropenic fever/sepsis. Overall, neutropenia Grade 4 that lasted &gt; 1 week and sepsis were noticed in 3% and 2% of cycles, respectively. Because no MTD was reached, the planned Phase II trial was not initiated. However, the patients from Phase I were followed until they developed progressive disease and, among them, 9 patients (32%) obtained an objective response (according to Response Evaluation Criteria in Solid Tumors (RECIST) or CA125 response criteria). CONCLUSIONS. Combined topotecan and oral etoposide was inappropriate in patients with recurrent ovarian carcinoma because of unpredictable hematologic toxicity. However, the high objective response rate highlighted the potential additive effect of topoisomerase I and II inhibitors.},
  author       = {Gronlund, B and Engelholm, SA and Horvath, G and Maenpaa, J and Ridderheim, Mona},
  issn         = {1097-0142},
  keyword      = {topoisomerase inhibitor,etoposide,topotecan,chemotherapy,second-line treatment,ovarian neoplasms,recurrence,Phase 1,response},
  language     = {eng},
  number       = {7},
  pages        = {1388--1396},
  publisher    = {John Wiley & Sons},
  series       = {Cancer},
  title        = {Sequential topotecan and oral etoposide in recurrent ovarian carcinoma pretreated with platinum-taxane - Results from a multicenter phase I/II study},
  url          = {http://dx.doi.org/10.1002/cncr.20921},
  volume       = {103},
  year         = {2005},
}