Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial

Noriyuki Katsumata, Makoto Yasuda, Fumiaki Takahashi, Seiji Isonishi, Toshiko Jobo, Daisuke Aoki, Hiroshi Tsuda, Toru Sugiyama, Shoji Kodama, Eizo Kimura, Kazunori Ochiai, Kiichiro Noda

Research output: Contribution to journalArticle

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Abstract

Background: Paclitaxel and carboplatin given every 3 weeks is standard treatment for advanced ovarian carcinoma. Attempts to improve patient survival by including other drugs have yielded disappointing results. We compared a conventional regimen of paclitaxel and carboplatin with a dose-dense weekly regimen in women with advanced ovarian cancer. Methods: Patients with stage II to IV epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer were eligible for enrolment in this phase 3, open-label, randomised controlled trial at 85 centres in Japan. Patients were randomly assigned by computer-generated randomisation sequence to receive six cycles of either paclitaxel (180 mg/m2; 3-h intravenous infusion) plus carboplatin (area under the curve [AUC] 6 mg/mL per min), given on day 1 of a 21-day cycle (conventional regimen; n=320), or dose-dense paclitaxel (80 mg/m2; 1-h intravenous infusion) given on days 1, 8, and 15 plus carboplatin given on day 1 of a 21-day cycle (dose-dense regimen; n=317). The primary endpoint was progression-free survival. Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov, number NCT00226915. Findings: 631 of the 637 enrolled patients were eligible for treatment and were included in the ITT population (dose-dense regimen, n=312; conventional regimen, n=319). Median progression-free survival was longer in the dose-dense treatment group (28·0 months, 95% CI 22·3-35·4) than in the conventional treatment group (17·2 months, 15·7-21·1; hazard ratio [HR] 0·71; 95% CI 0·58-0·88; p=0·0015). Overall survival at 3 years was higher in the dose-dense regimen group (72·1%) than in the conventional treatment group (65·1%; HR 0·75, 0·57-0·98; p=0·03). 165 patients assigned to the dose-dense regimen and 117 assigned to the conventional regimen discontinued treatment early. Reasons for participant dropout were balanced between the groups, apart from withdrawal because of toxicity, which was higher in the dose-dense regimen group than in the conventional regimen group (n=113 vs n=69). The most common adverse event was neutropenia (dose-dense regimen, 286 [92%] of 312; conventional regimen, 276 [88%] of 314). The frequency of grade 3 and 4 anaemia was higher in the dose-dense treatment group (214 [69%]) than in the conventional treatment group (137 [44%]; p<0·0001). The frequencies of other toxic effects were similar between groups. Interpretation: Dose-dense weekly paclitaxel plus carboplatin improved survival compared with the conventional regimen and represents a new treatment option in women with advanced epithelial ovarian cancer. Funding: Bristol-Myers Squibb.

Original languageEnglish
Pages (from-to)1331-1338
Number of pages8
JournalThe Lancet
Volume374
Issue number9698
DOIs
Publication statusPublished - 2009

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Carboplatin
Paclitaxel
Ovarian Neoplasms
Randomized Controlled Trials
Fallopian Tube Neoplasms
Therapeutics
Intravenous Infusions
Disease-Free Survival
Survival
Intention to Treat Analysis
Poisons
Random Allocation
Neutropenia
Area Under Curve
Anemia
Japan
Carcinoma

ASJC Scopus subject areas

  • Medicine(all)

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Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer : a phase 3, open-label, randomised controlled trial. / Katsumata, Noriyuki; Yasuda, Makoto; Takahashi, Fumiaki; Isonishi, Seiji; Jobo, Toshiko; Aoki, Daisuke; Tsuda, Hiroshi; Sugiyama, Toru; Kodama, Shoji; Kimura, Eizo; Ochiai, Kazunori; Noda, Kiichiro.

In: The Lancet, Vol. 374, No. 9698, 2009, p. 1331-1338.

Research output: Contribution to journalArticle

Katsumata, N, Yasuda, M, Takahashi, F, Isonishi, S, Jobo, T, Aoki, D, Tsuda, H, Sugiyama, T, Kodama, S, Kimura, E, Ochiai, K & Noda, K 2009, 'Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial', The Lancet, vol. 374, no. 9698, pp. 1331-1338. https://doi.org/10.1016/S0140-6736(09)61157-0
Katsumata, Noriyuki ; Yasuda, Makoto ; Takahashi, Fumiaki ; Isonishi, Seiji ; Jobo, Toshiko ; Aoki, Daisuke ; Tsuda, Hiroshi ; Sugiyama, Toru ; Kodama, Shoji ; Kimura, Eizo ; Ochiai, Kazunori ; Noda, Kiichiro. / Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer : a phase 3, open-label, randomised controlled trial. In: The Lancet. 2009 ; Vol. 374, No. 9698. pp. 1331-1338.
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T1 - Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer

T2 - a phase 3, open-label, randomised controlled trial

AU - Katsumata, Noriyuki

AU - Yasuda, Makoto

AU - Takahashi, Fumiaki

AU - Isonishi, Seiji

AU - Jobo, Toshiko

AU - Aoki, Daisuke

AU - Tsuda, Hiroshi

AU - Sugiyama, Toru

AU - Kodama, Shoji

AU - Kimura, Eizo

AU - Ochiai, Kazunori

AU - Noda, Kiichiro

PY - 2009

Y1 - 2009

N2 - Background: Paclitaxel and carboplatin given every 3 weeks is standard treatment for advanced ovarian carcinoma. Attempts to improve patient survival by including other drugs have yielded disappointing results. We compared a conventional regimen of paclitaxel and carboplatin with a dose-dense weekly regimen in women with advanced ovarian cancer. Methods: Patients with stage II to IV epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer were eligible for enrolment in this phase 3, open-label, randomised controlled trial at 85 centres in Japan. Patients were randomly assigned by computer-generated randomisation sequence to receive six cycles of either paclitaxel (180 mg/m2; 3-h intravenous infusion) plus carboplatin (area under the curve [AUC] 6 mg/mL per min), given on day 1 of a 21-day cycle (conventional regimen; n=320), or dose-dense paclitaxel (80 mg/m2; 1-h intravenous infusion) given on days 1, 8, and 15 plus carboplatin given on day 1 of a 21-day cycle (dose-dense regimen; n=317). The primary endpoint was progression-free survival. Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov, number NCT00226915. Findings: 631 of the 637 enrolled patients were eligible for treatment and were included in the ITT population (dose-dense regimen, n=312; conventional regimen, n=319). Median progression-free survival was longer in the dose-dense treatment group (28·0 months, 95% CI 22·3-35·4) than in the conventional treatment group (17·2 months, 15·7-21·1; hazard ratio [HR] 0·71; 95% CI 0·58-0·88; p=0·0015). Overall survival at 3 years was higher in the dose-dense regimen group (72·1%) than in the conventional treatment group (65·1%; HR 0·75, 0·57-0·98; p=0·03). 165 patients assigned to the dose-dense regimen and 117 assigned to the conventional regimen discontinued treatment early. Reasons for participant dropout were balanced between the groups, apart from withdrawal because of toxicity, which was higher in the dose-dense regimen group than in the conventional regimen group (n=113 vs n=69). The most common adverse event was neutropenia (dose-dense regimen, 286 [92%] of 312; conventional regimen, 276 [88%] of 314). The frequency of grade 3 and 4 anaemia was higher in the dose-dense treatment group (214 [69%]) than in the conventional treatment group (137 [44%]; p<0·0001). The frequencies of other toxic effects were similar between groups. Interpretation: Dose-dense weekly paclitaxel plus carboplatin improved survival compared with the conventional regimen and represents a new treatment option in women with advanced epithelial ovarian cancer. Funding: Bristol-Myers Squibb.

AB - Background: Paclitaxel and carboplatin given every 3 weeks is standard treatment for advanced ovarian carcinoma. Attempts to improve patient survival by including other drugs have yielded disappointing results. We compared a conventional regimen of paclitaxel and carboplatin with a dose-dense weekly regimen in women with advanced ovarian cancer. Methods: Patients with stage II to IV epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer were eligible for enrolment in this phase 3, open-label, randomised controlled trial at 85 centres in Japan. Patients were randomly assigned by computer-generated randomisation sequence to receive six cycles of either paclitaxel (180 mg/m2; 3-h intravenous infusion) plus carboplatin (area under the curve [AUC] 6 mg/mL per min), given on day 1 of a 21-day cycle (conventional regimen; n=320), or dose-dense paclitaxel (80 mg/m2; 1-h intravenous infusion) given on days 1, 8, and 15 plus carboplatin given on day 1 of a 21-day cycle (dose-dense regimen; n=317). The primary endpoint was progression-free survival. Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov, number NCT00226915. Findings: 631 of the 637 enrolled patients were eligible for treatment and were included in the ITT population (dose-dense regimen, n=312; conventional regimen, n=319). Median progression-free survival was longer in the dose-dense treatment group (28·0 months, 95% CI 22·3-35·4) than in the conventional treatment group (17·2 months, 15·7-21·1; hazard ratio [HR] 0·71; 95% CI 0·58-0·88; p=0·0015). Overall survival at 3 years was higher in the dose-dense regimen group (72·1%) than in the conventional treatment group (65·1%; HR 0·75, 0·57-0·98; p=0·03). 165 patients assigned to the dose-dense regimen and 117 assigned to the conventional regimen discontinued treatment early. Reasons for participant dropout were balanced between the groups, apart from withdrawal because of toxicity, which was higher in the dose-dense regimen group than in the conventional regimen group (n=113 vs n=69). The most common adverse event was neutropenia (dose-dense regimen, 286 [92%] of 312; conventional regimen, 276 [88%] of 314). The frequency of grade 3 and 4 anaemia was higher in the dose-dense treatment group (214 [69%]) than in the conventional treatment group (137 [44%]; p<0·0001). The frequencies of other toxic effects were similar between groups. Interpretation: Dose-dense weekly paclitaxel plus carboplatin improved survival compared with the conventional regimen and represents a new treatment option in women with advanced epithelial ovarian cancer. Funding: Bristol-Myers Squibb.

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