Cargando…
A phase I study of irinotecan and pegylated liposomal doxorubicin in recurrent ovarian cancer (Tohoku Gynecologic Cancer Unit 104 study)
PURPOSE: A phase I clinical study was conducted to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of irinotecan hydrochloride (CPT-11) in CPT-11/pegylated liposomal doxorubicin (PLD) combination therapy, a novel treatment regimen for platinum- and taxane-resistant recurrent...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000409/ https://www.ncbi.nlm.nih.gov/pubmed/24585045 http://dx.doi.org/10.1007/s00280-014-2418-8 |
_version_ | 1782313615245705216 |
---|---|
author | Shoji, Tadahiro Takatori, Eriko Kaido, Yoshitaka Omi, Hideo Yokoyama, Yoshihito Mizunuma, Hideki Kaiho, Michiko Otsuki, Takeo Takano, Tadao Yaegashi, Nobuo Nishiyama, Hiroshi Fujimori, Keiya Sugiyama, Toru |
author_facet | Shoji, Tadahiro Takatori, Eriko Kaido, Yoshitaka Omi, Hideo Yokoyama, Yoshihito Mizunuma, Hideki Kaiho, Michiko Otsuki, Takeo Takano, Tadao Yaegashi, Nobuo Nishiyama, Hiroshi Fujimori, Keiya Sugiyama, Toru |
author_sort | Shoji, Tadahiro |
collection | PubMed |
description | PURPOSE: A phase I clinical study was conducted to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of irinotecan hydrochloride (CPT-11) in CPT-11/pegylated liposomal doxorubicin (PLD) combination therapy, a novel treatment regimen for platinum- and taxane-resistant recurrent ovarian cancer. METHODS: Pegylated liposomal doxorubicin was administered intravenously on day 3 at a fixed dose of 30 mg/m(2). CPT-11 was administered intravenously on days 1 and 15, at a dose of 50 mg/m(2) on both days. One course of chemotherapy was 28 days, and patients were given a maximum of six courses, with the CPT-11 dose being increased in increments of 10 mg/m(2) (level 1, 50 mg/m(2); level 2, 60 mg/m(2); level 3, 70 mg/m(2); level 4, 80 mg/m(2)) to determine MTD and RD. RESULTS: During the period from April 2010 to March 2013, three patients were enrolled for each level. In the first course, no dose-limiting toxicity occurred in any of the patients. Grade 4 neutropenia was observed in two of three patients at level 4. At level 4, the antitumor effect was a partial response (PR) in two of the three patients and stable disease (SD) in one. At level 3, one of the three patients showed PR and two had SD. At level 4, the start of the next course was postponed in two of three patients. In addition, one patient at level 4 experienced hemotoxicity that met the criteria for dose reduction in the next course. The above results suggested that administration of CPT-11 at dose level 5 (90 mg/m(2)) would result in more patients with severe neutropenia and in more patients requiring postponement of the next course or a dose reduction. Based on the above, the RD of CPT-11 was determined to be 80 mg/m(2). CONCLUSIONS: The results suggest that CPT-11/PLD combination therapy for recurrent ovarian cancer is a useful treatment method with a high response rate and manageable adverse reactions. In the future phase II study, the safety and efficacy of this therapy will be assessed at 80 mg/m(2) of CPT-11 and 30 mg/m(2) of PLD. |
format | Online Article Text |
id | pubmed-4000409 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-40004092014-05-07 A phase I study of irinotecan and pegylated liposomal doxorubicin in recurrent ovarian cancer (Tohoku Gynecologic Cancer Unit 104 study) Shoji, Tadahiro Takatori, Eriko Kaido, Yoshitaka Omi, Hideo Yokoyama, Yoshihito Mizunuma, Hideki Kaiho, Michiko Otsuki, Takeo Takano, Tadao Yaegashi, Nobuo Nishiyama, Hiroshi Fujimori, Keiya Sugiyama, Toru Cancer Chemother Pharmacol Original Article PURPOSE: A phase I clinical study was conducted to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of irinotecan hydrochloride (CPT-11) in CPT-11/pegylated liposomal doxorubicin (PLD) combination therapy, a novel treatment regimen for platinum- and taxane-resistant recurrent ovarian cancer. METHODS: Pegylated liposomal doxorubicin was administered intravenously on day 3 at a fixed dose of 30 mg/m(2). CPT-11 was administered intravenously on days 1 and 15, at a dose of 50 mg/m(2) on both days. One course of chemotherapy was 28 days, and patients were given a maximum of six courses, with the CPT-11 dose being increased in increments of 10 mg/m(2) (level 1, 50 mg/m(2); level 2, 60 mg/m(2); level 3, 70 mg/m(2); level 4, 80 mg/m(2)) to determine MTD and RD. RESULTS: During the period from April 2010 to March 2013, three patients were enrolled for each level. In the first course, no dose-limiting toxicity occurred in any of the patients. Grade 4 neutropenia was observed in two of three patients at level 4. At level 4, the antitumor effect was a partial response (PR) in two of the three patients and stable disease (SD) in one. At level 3, one of the three patients showed PR and two had SD. At level 4, the start of the next course was postponed in two of three patients. In addition, one patient at level 4 experienced hemotoxicity that met the criteria for dose reduction in the next course. The above results suggested that administration of CPT-11 at dose level 5 (90 mg/m(2)) would result in more patients with severe neutropenia and in more patients requiring postponement of the next course or a dose reduction. Based on the above, the RD of CPT-11 was determined to be 80 mg/m(2). CONCLUSIONS: The results suggest that CPT-11/PLD combination therapy for recurrent ovarian cancer is a useful treatment method with a high response rate and manageable adverse reactions. In the future phase II study, the safety and efficacy of this therapy will be assessed at 80 mg/m(2) of CPT-11 and 30 mg/m(2) of PLD. Springer Berlin Heidelberg 2014-03-01 2014 /pmc/articles/PMC4000409/ /pubmed/24585045 http://dx.doi.org/10.1007/s00280-014-2418-8 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/4.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Original Article Shoji, Tadahiro Takatori, Eriko Kaido, Yoshitaka Omi, Hideo Yokoyama, Yoshihito Mizunuma, Hideki Kaiho, Michiko Otsuki, Takeo Takano, Tadao Yaegashi, Nobuo Nishiyama, Hiroshi Fujimori, Keiya Sugiyama, Toru A phase I study of irinotecan and pegylated liposomal doxorubicin in recurrent ovarian cancer (Tohoku Gynecologic Cancer Unit 104 study) |
title | A phase I study of irinotecan and pegylated liposomal doxorubicin in recurrent ovarian cancer (Tohoku Gynecologic Cancer Unit 104 study) |
title_full | A phase I study of irinotecan and pegylated liposomal doxorubicin in recurrent ovarian cancer (Tohoku Gynecologic Cancer Unit 104 study) |
title_fullStr | A phase I study of irinotecan and pegylated liposomal doxorubicin in recurrent ovarian cancer (Tohoku Gynecologic Cancer Unit 104 study) |
title_full_unstemmed | A phase I study of irinotecan and pegylated liposomal doxorubicin in recurrent ovarian cancer (Tohoku Gynecologic Cancer Unit 104 study) |
title_short | A phase I study of irinotecan and pegylated liposomal doxorubicin in recurrent ovarian cancer (Tohoku Gynecologic Cancer Unit 104 study) |
title_sort | phase i study of irinotecan and pegylated liposomal doxorubicin in recurrent ovarian cancer (tohoku gynecologic cancer unit 104 study) |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000409/ https://www.ncbi.nlm.nih.gov/pubmed/24585045 http://dx.doi.org/10.1007/s00280-014-2418-8 |
work_keys_str_mv | AT shojitadahiro aphaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT takatorieriko aphaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT kaidoyoshitaka aphaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT omihideo aphaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT yokoyamayoshihito aphaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT mizunumahideki aphaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT kaihomichiko aphaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT otsukitakeo aphaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT takanotadao aphaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT yaegashinobuo aphaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT nishiyamahiroshi aphaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT fujimorikeiya aphaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT sugiyamatoru aphaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT shojitadahiro phaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT takatorieriko phaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT kaidoyoshitaka phaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT omihideo phaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT yokoyamayoshihito phaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT mizunumahideki phaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT kaihomichiko phaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT otsukitakeo phaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT takanotadao phaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT yaegashinobuo phaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT nishiyamahiroshi phaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT fujimorikeiya phaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study AT sugiyamatoru phaseistudyofirinotecanandpegylatedliposomaldoxorubicininrecurrentovariancancertohokugynecologiccancerunit104study |