European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: High-dose versus low-dose and long versus short infusion

Elizabeth A. Eisenhauer, Wim W. Ten Bokkel Huinink, Kenneth D. Swenerton, Luca Gianni, James Myles, Maria E L Van Der Burg, Ian Kerr, Jan B. Vermorken, Katharina Buser, Nicoletta Colombo, Monica Bacon, Pedro Santabárbara, Nicole Onetto, Benjamin Winograd, Renzo Canetta

Research output: Contribution to journalArticle

Abstract

Purpose: Taxol (paclitaxel; Bristol-Myers Squibb, Wallingford, CT) is a new anticancer agent with activity in a number of human tumors, including epithelial ovarian cancer. In nonrandomized trials, doses studied have ranged from 135 mg/m2 to 250 mg/m2 administered over 24 hours with premedication to avoid hypersensitivity reactions (HSRs). This study addressed two questions: the dose-response relationship of Taxol in relapsed ovarian cancer and the safety of a short infusion given with premedication. Methods: Women with platinum-pretreated epithelial ovarian cancer and measurable recurrent disease were randomized in a bifactorial design to receive either 175 or 135 mg/m2 of Taxol over either 24 or 3 hours. Major end points were the frequency of significant HSRs and objective response rate. Secondary end points were progression-free and overall survival. Results: Of 407 patients randomized, 391 were eligible and 382 assessable for response. Analysis was performed according to the bifactorial design. Severe HSRs were rare (1.5% patients) and were not affected by either dose or schedule. Response was slightly higher at the 175-mg/m2 dose (20%) than at 135 mg/m2 (15%), but this was not statistically significant (P = .2). However, progression-free survival was significantly longer in the high-dose group (19 v 14 weeks; P = .02). Significantly more neutropenia was seen when Taxol was administered as a 24-hour infusion. Response rates were similar in the 24- and 3-hour groups (19% and 16%, respectively; P = .6). No survival differences were noted. Conclusion: The 3-hour infusion of Taxol is safe when given with premedication and is associated with less neutropenia. There is a modest dose effect with longer time to progression at 175 mg/m2. The observation that longer infusion produces more myelosuppression but does not yield higher response rates should lead to further studies to determine the optimal dose and schedule of this interesting new agent.

Original languageEnglish
Pages (from-to)2654-2666
Number of pages13
JournalJournal of Clinical Oncology
Volume12
Issue number12
Publication statusPublished - Dec 1994

Fingerprint

Paclitaxel
Ovarian Neoplasms
Premedication
Hypersensitivity
Neutropenia
Disease-Free Survival
Appointments and Schedules
Platinum
Antineoplastic Agents
Safety
Survival
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Eisenhauer, E. A., Ten Bokkel Huinink, W. W., Swenerton, K. D., Gianni, L., Myles, J., Van Der Burg, M. E. L., ... Canetta, R. (1994). European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: High-dose versus low-dose and long versus short infusion. Journal of Clinical Oncology, 12(12), 2654-2666.

European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer : High-dose versus low-dose and long versus short infusion. / Eisenhauer, Elizabeth A.; Ten Bokkel Huinink, Wim W.; Swenerton, Kenneth D.; Gianni, Luca; Myles, James; Van Der Burg, Maria E L; Kerr, Ian; Vermorken, Jan B.; Buser, Katharina; Colombo, Nicoletta; Bacon, Monica; Santabárbara, Pedro; Onetto, Nicole; Winograd, Benjamin; Canetta, Renzo.

In: Journal of Clinical Oncology, Vol. 12, No. 12, 12.1994, p. 2654-2666.

Research output: Contribution to journalArticle

Eisenhauer, EA, Ten Bokkel Huinink, WW, Swenerton, KD, Gianni, L, Myles, J, Van Der Burg, MEL, Kerr, I, Vermorken, JB, Buser, K, Colombo, N, Bacon, M, Santabárbara, P, Onetto, N, Winograd, B & Canetta, R 1994, 'European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: High-dose versus low-dose and long versus short infusion', Journal of Clinical Oncology, vol. 12, no. 12, pp. 2654-2666.
Eisenhauer EA, Ten Bokkel Huinink WW, Swenerton KD, Gianni L, Myles J, Van Der Burg MEL et al. European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: High-dose versus low-dose and long versus short infusion. Journal of Clinical Oncology. 1994 Dec;12(12):2654-2666.
Eisenhauer, Elizabeth A. ; Ten Bokkel Huinink, Wim W. ; Swenerton, Kenneth D. ; Gianni, Luca ; Myles, James ; Van Der Burg, Maria E L ; Kerr, Ian ; Vermorken, Jan B. ; Buser, Katharina ; Colombo, Nicoletta ; Bacon, Monica ; Santabárbara, Pedro ; Onetto, Nicole ; Winograd, Benjamin ; Canetta, Renzo. / European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer : High-dose versus low-dose and long versus short infusion. In: Journal of Clinical Oncology. 1994 ; Vol. 12, No. 12. pp. 2654-2666.
@article{468a2f8f921441259a25fe46a34730df,
title = "European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: High-dose versus low-dose and long versus short infusion",
abstract = "Purpose: Taxol (paclitaxel; Bristol-Myers Squibb, Wallingford, CT) is a new anticancer agent with activity in a number of human tumors, including epithelial ovarian cancer. In nonrandomized trials, doses studied have ranged from 135 mg/m2 to 250 mg/m2 administered over 24 hours with premedication to avoid hypersensitivity reactions (HSRs). This study addressed two questions: the dose-response relationship of Taxol in relapsed ovarian cancer and the safety of a short infusion given with premedication. Methods: Women with platinum-pretreated epithelial ovarian cancer and measurable recurrent disease were randomized in a bifactorial design to receive either 175 or 135 mg/m2 of Taxol over either 24 or 3 hours. Major end points were the frequency of significant HSRs and objective response rate. Secondary end points were progression-free and overall survival. Results: Of 407 patients randomized, 391 were eligible and 382 assessable for response. Analysis was performed according to the bifactorial design. Severe HSRs were rare (1.5{\%} patients) and were not affected by either dose or schedule. Response was slightly higher at the 175-mg/m2 dose (20{\%}) than at 135 mg/m2 (15{\%}), but this was not statistically significant (P = .2). However, progression-free survival was significantly longer in the high-dose group (19 v 14 weeks; P = .02). Significantly more neutropenia was seen when Taxol was administered as a 24-hour infusion. Response rates were similar in the 24- and 3-hour groups (19{\%} and 16{\%}, respectively; P = .6). No survival differences were noted. Conclusion: The 3-hour infusion of Taxol is safe when given with premedication and is associated with less neutropenia. There is a modest dose effect with longer time to progression at 175 mg/m2. The observation that longer infusion produces more myelosuppression but does not yield higher response rates should lead to further studies to determine the optimal dose and schedule of this interesting new agent.",
author = "Eisenhauer, {Elizabeth A.} and {Ten Bokkel Huinink}, {Wim W.} and Swenerton, {Kenneth D.} and Luca Gianni and James Myles and {Van Der Burg}, {Maria E L} and Ian Kerr and Vermorken, {Jan B.} and Katharina Buser and Nicoletta Colombo and Monica Bacon and Pedro Santab{\'a}rbara and Nicole Onetto and Benjamin Winograd and Renzo Canetta",
year = "1994",
month = "12",
language = "English",
volume = "12",
pages = "2654--2666",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "12",

}

TY - JOUR

T1 - European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer

T2 - High-dose versus low-dose and long versus short infusion

AU - Eisenhauer, Elizabeth A.

AU - Ten Bokkel Huinink, Wim W.

AU - Swenerton, Kenneth D.

AU - Gianni, Luca

AU - Myles, James

AU - Van Der Burg, Maria E L

AU - Kerr, Ian

AU - Vermorken, Jan B.

AU - Buser, Katharina

AU - Colombo, Nicoletta

AU - Bacon, Monica

AU - Santabárbara, Pedro

AU - Onetto, Nicole

AU - Winograd, Benjamin

AU - Canetta, Renzo

PY - 1994/12

Y1 - 1994/12

N2 - Purpose: Taxol (paclitaxel; Bristol-Myers Squibb, Wallingford, CT) is a new anticancer agent with activity in a number of human tumors, including epithelial ovarian cancer. In nonrandomized trials, doses studied have ranged from 135 mg/m2 to 250 mg/m2 administered over 24 hours with premedication to avoid hypersensitivity reactions (HSRs). This study addressed two questions: the dose-response relationship of Taxol in relapsed ovarian cancer and the safety of a short infusion given with premedication. Methods: Women with platinum-pretreated epithelial ovarian cancer and measurable recurrent disease were randomized in a bifactorial design to receive either 175 or 135 mg/m2 of Taxol over either 24 or 3 hours. Major end points were the frequency of significant HSRs and objective response rate. Secondary end points were progression-free and overall survival. Results: Of 407 patients randomized, 391 were eligible and 382 assessable for response. Analysis was performed according to the bifactorial design. Severe HSRs were rare (1.5% patients) and were not affected by either dose or schedule. Response was slightly higher at the 175-mg/m2 dose (20%) than at 135 mg/m2 (15%), but this was not statistically significant (P = .2). However, progression-free survival was significantly longer in the high-dose group (19 v 14 weeks; P = .02). Significantly more neutropenia was seen when Taxol was administered as a 24-hour infusion. Response rates were similar in the 24- and 3-hour groups (19% and 16%, respectively; P = .6). No survival differences were noted. Conclusion: The 3-hour infusion of Taxol is safe when given with premedication and is associated with less neutropenia. There is a modest dose effect with longer time to progression at 175 mg/m2. The observation that longer infusion produces more myelosuppression but does not yield higher response rates should lead to further studies to determine the optimal dose and schedule of this interesting new agent.

AB - Purpose: Taxol (paclitaxel; Bristol-Myers Squibb, Wallingford, CT) is a new anticancer agent with activity in a number of human tumors, including epithelial ovarian cancer. In nonrandomized trials, doses studied have ranged from 135 mg/m2 to 250 mg/m2 administered over 24 hours with premedication to avoid hypersensitivity reactions (HSRs). This study addressed two questions: the dose-response relationship of Taxol in relapsed ovarian cancer and the safety of a short infusion given with premedication. Methods: Women with platinum-pretreated epithelial ovarian cancer and measurable recurrent disease were randomized in a bifactorial design to receive either 175 or 135 mg/m2 of Taxol over either 24 or 3 hours. Major end points were the frequency of significant HSRs and objective response rate. Secondary end points were progression-free and overall survival. Results: Of 407 patients randomized, 391 were eligible and 382 assessable for response. Analysis was performed according to the bifactorial design. Severe HSRs were rare (1.5% patients) and were not affected by either dose or schedule. Response was slightly higher at the 175-mg/m2 dose (20%) than at 135 mg/m2 (15%), but this was not statistically significant (P = .2). However, progression-free survival was significantly longer in the high-dose group (19 v 14 weeks; P = .02). Significantly more neutropenia was seen when Taxol was administered as a 24-hour infusion. Response rates were similar in the 24- and 3-hour groups (19% and 16%, respectively; P = .6). No survival differences were noted. Conclusion: The 3-hour infusion of Taxol is safe when given with premedication and is associated with less neutropenia. There is a modest dose effect with longer time to progression at 175 mg/m2. The observation that longer infusion produces more myelosuppression but does not yield higher response rates should lead to further studies to determine the optimal dose and schedule of this interesting new agent.

UR - http://www.scopus.com/inward/record.url?scp=0027999966&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027999966&partnerID=8YFLogxK

M3 - Article

C2 - 7989941

AN - SCOPUS:0027999966

VL - 12

SP - 2654

EP - 2666

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 12

ER -