Weekly vs. every-3-week paclitaxel and carboplatin for ovarian cancer

J. K. Chan, M. F. Brady, R. T. Penson, H. Huang, M. J. Birrer, J. L. Walker, P. A. DiSilvestro, S. C. Rubin, L. P. Martin, S. A. Davidson, W. K. Huh, D. M. O'Malley, M. P. Boente, Helen Michael, B. J. Monk

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

BACKGROUND A dose-dense weekly schedule of paclitaxel (resulting in a greater frequency of drug delivery) plus carboplatin every 3 weeks or the addition of bevacizumab to paclitaxel and carboplatin administered every 3 weeks has shown efficacy in ovarian cancer. We proposed to determine whether dose-dense weekly paclitaxel and carboplatin would prolong progression-free survival as compared with paclitaxel and carboplatin administered every 3 weeks among patients receiving and those not receiving bevacizumab. METHODS We prospectively stratified patients according to whether they elected to receive bevacizumab and then randomly assigned them to receive either paclitaxel, administered intravenously at a dose of 175 mg per square meter of body-surface area every 3 weeks, plus carboplatin (dose equivalent to an area under the curve [AUC] of 6) for six cycles or paclitaxel, administered weekly at a dose of 80 mg per square meter, plus carboplatin (AUC, 6) for six cycles. The primary end point was progression-free survival. RESULTS A total of 692 patients were enrolled, 84% of whom opted to receive bevacizumab. In the intention-to-treat analysis, weekly paclitaxel was not associated with longer progressionfree survival than paclitaxel administered every 3 weeks (14.7 months and 14.0 months, respectively; hazard ratio for disease progression or death, 0.89; 95% confidence interval [CI], 0.74 to 1.06; P = 0.18). Among patients who did not receive bevacizumab, weekly paclitaxel was associated with progression-free survival that was 3.9 months longer than that observed with paclitaxel administered every 3 weeks (14.2 vs. 10.3 months; hazard ratio, 0.62; 95% CI, 0.40 to 0.95; P = 0.03). However, among patients who received bevacizumab, weekly paclitaxel did not significantly prolong progression-free survival, as compared with paclitaxel administered every 3 weeks (14.9 months and 14.7 months, respectively; hazard ratio, 0.99; 95% CI, 0.83 to 1.20; P = 0.60). A test for interaction that assessed homogeneity of the treatment effect showed a significant difference between treatment with bevacizumab and without bevacizumab (P = 0.047). Patients who received weekly paclitaxel had a higher rate of grade 3 or 4 anemia than did those who received paclitaxel every 3 weeks (36% vs. 16%), as well as a higher rate of grade 2 to 4 sensory neuropathy (26% vs. 18%); however, they had a lower rate of grade 3 or 4 neutropenia (72% vs. 83%). CONCLUSIONS Overall, weekly paclitaxel, as compared with paclitaxel administered every 3 weeks, did not prolong progression-free survival among patients with ovarian cancer. (Funded by the National Cancer Institute and Genentech; GOG-0262 ClinicalTrials.gov number, NCT01167712.).

Original languageEnglish (US)
Pages (from-to)738-748
Number of pages11
JournalNew England Journal of Medicine
Volume374
Issue number8
DOIs
StatePublished - Feb 25 2016

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Carboplatin
Paclitaxel
Ovarian Neoplasms
Disease-Free Survival
Confidence Intervals
Area Under Curve
Intention to Treat Analysis
National Cancer Institute (U.S.)
Bevacizumab
Body Surface Area
Neutropenia

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Chan, J. K., Brady, M. F., Penson, R. T., Huang, H., Birrer, M. J., Walker, J. L., ... Monk, B. J. (2016). Weekly vs. every-3-week paclitaxel and carboplatin for ovarian cancer. New England Journal of Medicine, 374(8), 738-748. https://doi.org/10.1056/NEJMoa1505067

Weekly vs. every-3-week paclitaxel and carboplatin for ovarian cancer. / Chan, J. K.; Brady, M. F.; Penson, R. T.; Huang, H.; Birrer, M. J.; Walker, J. L.; DiSilvestro, P. A.; Rubin, S. C.; Martin, L. P.; Davidson, S. A.; Huh, W. K.; O'Malley, D. M.; Boente, M. P.; Michael, Helen; Monk, B. J.

In: New England Journal of Medicine, Vol. 374, No. 8, 25.02.2016, p. 738-748.

Research output: Contribution to journalArticle

Chan, JK, Brady, MF, Penson, RT, Huang, H, Birrer, MJ, Walker, JL, DiSilvestro, PA, Rubin, SC, Martin, LP, Davidson, SA, Huh, WK, O'Malley, DM, Boente, MP, Michael, H & Monk, BJ 2016, 'Weekly vs. every-3-week paclitaxel and carboplatin for ovarian cancer', New England Journal of Medicine, vol. 374, no. 8, pp. 738-748. https://doi.org/10.1056/NEJMoa1505067
Chan JK, Brady MF, Penson RT, Huang H, Birrer MJ, Walker JL et al. Weekly vs. every-3-week paclitaxel and carboplatin for ovarian cancer. New England Journal of Medicine. 2016 Feb 25;374(8):738-748. https://doi.org/10.1056/NEJMoa1505067
Chan, J. K. ; Brady, M. F. ; Penson, R. T. ; Huang, H. ; Birrer, M. J. ; Walker, J. L. ; DiSilvestro, P. A. ; Rubin, S. C. ; Martin, L. P. ; Davidson, S. A. ; Huh, W. K. ; O'Malley, D. M. ; Boente, M. P. ; Michael, Helen ; Monk, B. J. / Weekly vs. every-3-week paclitaxel and carboplatin for ovarian cancer. In: New England Journal of Medicine. 2016 ; Vol. 374, No. 8. pp. 738-748.
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title = "Weekly vs. every-3-week paclitaxel and carboplatin for ovarian cancer",
abstract = "BACKGROUND A dose-dense weekly schedule of paclitaxel (resulting in a greater frequency of drug delivery) plus carboplatin every 3 weeks or the addition of bevacizumab to paclitaxel and carboplatin administered every 3 weeks has shown efficacy in ovarian cancer. We proposed to determine whether dose-dense weekly paclitaxel and carboplatin would prolong progression-free survival as compared with paclitaxel and carboplatin administered every 3 weeks among patients receiving and those not receiving bevacizumab. METHODS We prospectively stratified patients according to whether they elected to receive bevacizumab and then randomly assigned them to receive either paclitaxel, administered intravenously at a dose of 175 mg per square meter of body-surface area every 3 weeks, plus carboplatin (dose equivalent to an area under the curve [AUC] of 6) for six cycles or paclitaxel, administered weekly at a dose of 80 mg per square meter, plus carboplatin (AUC, 6) for six cycles. The primary end point was progression-free survival. RESULTS A total of 692 patients were enrolled, 84{\%} of whom opted to receive bevacizumab. In the intention-to-treat analysis, weekly paclitaxel was not associated with longer progressionfree survival than paclitaxel administered every 3 weeks (14.7 months and 14.0 months, respectively; hazard ratio for disease progression or death, 0.89; 95{\%} confidence interval [CI], 0.74 to 1.06; P = 0.18). Among patients who did not receive bevacizumab, weekly paclitaxel was associated with progression-free survival that was 3.9 months longer than that observed with paclitaxel administered every 3 weeks (14.2 vs. 10.3 months; hazard ratio, 0.62; 95{\%} CI, 0.40 to 0.95; P = 0.03). However, among patients who received bevacizumab, weekly paclitaxel did not significantly prolong progression-free survival, as compared with paclitaxel administered every 3 weeks (14.9 months and 14.7 months, respectively; hazard ratio, 0.99; 95{\%} CI, 0.83 to 1.20; P = 0.60). A test for interaction that assessed homogeneity of the treatment effect showed a significant difference between treatment with bevacizumab and without bevacizumab (P = 0.047). Patients who received weekly paclitaxel had a higher rate of grade 3 or 4 anemia than did those who received paclitaxel every 3 weeks (36{\%} vs. 16{\%}), as well as a higher rate of grade 2 to 4 sensory neuropathy (26{\%} vs. 18{\%}); however, they had a lower rate of grade 3 or 4 neutropenia (72{\%} vs. 83{\%}). CONCLUSIONS Overall, weekly paclitaxel, as compared with paclitaxel administered every 3 weeks, did not prolong progression-free survival among patients with ovarian cancer. (Funded by the National Cancer Institute and Genentech; GOG-0262 ClinicalTrials.gov number, NCT01167712.).",
author = "Chan, {J. K.} and Brady, {M. F.} and Penson, {R. T.} and H. Huang and Birrer, {M. J.} and Walker, {J. L.} and DiSilvestro, {P. A.} and Rubin, {S. C.} and Martin, {L. P.} and Davidson, {S. A.} and Huh, {W. K.} and O'Malley, {D. M.} and Boente, {M. P.} and Helen Michael and Monk, {B. J.}",
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TY - JOUR

T1 - Weekly vs. every-3-week paclitaxel and carboplatin for ovarian cancer

AU - Chan, J. K.

AU - Brady, M. F.

AU - Penson, R. T.

AU - Huang, H.

AU - Birrer, M. J.

AU - Walker, J. L.

AU - DiSilvestro, P. A.

AU - Rubin, S. C.

AU - Martin, L. P.

AU - Davidson, S. A.

AU - Huh, W. K.

AU - O'Malley, D. M.

AU - Boente, M. P.

AU - Michael, Helen

AU - Monk, B. J.

PY - 2016/2/25

Y1 - 2016/2/25

N2 - BACKGROUND A dose-dense weekly schedule of paclitaxel (resulting in a greater frequency of drug delivery) plus carboplatin every 3 weeks or the addition of bevacizumab to paclitaxel and carboplatin administered every 3 weeks has shown efficacy in ovarian cancer. We proposed to determine whether dose-dense weekly paclitaxel and carboplatin would prolong progression-free survival as compared with paclitaxel and carboplatin administered every 3 weeks among patients receiving and those not receiving bevacizumab. METHODS We prospectively stratified patients according to whether they elected to receive bevacizumab and then randomly assigned them to receive either paclitaxel, administered intravenously at a dose of 175 mg per square meter of body-surface area every 3 weeks, plus carboplatin (dose equivalent to an area under the curve [AUC] of 6) for six cycles or paclitaxel, administered weekly at a dose of 80 mg per square meter, plus carboplatin (AUC, 6) for six cycles. The primary end point was progression-free survival. RESULTS A total of 692 patients were enrolled, 84% of whom opted to receive bevacizumab. In the intention-to-treat analysis, weekly paclitaxel was not associated with longer progressionfree survival than paclitaxel administered every 3 weeks (14.7 months and 14.0 months, respectively; hazard ratio for disease progression or death, 0.89; 95% confidence interval [CI], 0.74 to 1.06; P = 0.18). Among patients who did not receive bevacizumab, weekly paclitaxel was associated with progression-free survival that was 3.9 months longer than that observed with paclitaxel administered every 3 weeks (14.2 vs. 10.3 months; hazard ratio, 0.62; 95% CI, 0.40 to 0.95; P = 0.03). However, among patients who received bevacizumab, weekly paclitaxel did not significantly prolong progression-free survival, as compared with paclitaxel administered every 3 weeks (14.9 months and 14.7 months, respectively; hazard ratio, 0.99; 95% CI, 0.83 to 1.20; P = 0.60). A test for interaction that assessed homogeneity of the treatment effect showed a significant difference between treatment with bevacizumab and without bevacizumab (P = 0.047). Patients who received weekly paclitaxel had a higher rate of grade 3 or 4 anemia than did those who received paclitaxel every 3 weeks (36% vs. 16%), as well as a higher rate of grade 2 to 4 sensory neuropathy (26% vs. 18%); however, they had a lower rate of grade 3 or 4 neutropenia (72% vs. 83%). CONCLUSIONS Overall, weekly paclitaxel, as compared with paclitaxel administered every 3 weeks, did not prolong progression-free survival among patients with ovarian cancer. (Funded by the National Cancer Institute and Genentech; GOG-0262 ClinicalTrials.gov number, NCT01167712.).

AB - BACKGROUND A dose-dense weekly schedule of paclitaxel (resulting in a greater frequency of drug delivery) plus carboplatin every 3 weeks or the addition of bevacizumab to paclitaxel and carboplatin administered every 3 weeks has shown efficacy in ovarian cancer. We proposed to determine whether dose-dense weekly paclitaxel and carboplatin would prolong progression-free survival as compared with paclitaxel and carboplatin administered every 3 weeks among patients receiving and those not receiving bevacizumab. METHODS We prospectively stratified patients according to whether they elected to receive bevacizumab and then randomly assigned them to receive either paclitaxel, administered intravenously at a dose of 175 mg per square meter of body-surface area every 3 weeks, plus carboplatin (dose equivalent to an area under the curve [AUC] of 6) for six cycles or paclitaxel, administered weekly at a dose of 80 mg per square meter, plus carboplatin (AUC, 6) for six cycles. The primary end point was progression-free survival. RESULTS A total of 692 patients were enrolled, 84% of whom opted to receive bevacizumab. In the intention-to-treat analysis, weekly paclitaxel was not associated with longer progressionfree survival than paclitaxel administered every 3 weeks (14.7 months and 14.0 months, respectively; hazard ratio for disease progression or death, 0.89; 95% confidence interval [CI], 0.74 to 1.06; P = 0.18). Among patients who did not receive bevacizumab, weekly paclitaxel was associated with progression-free survival that was 3.9 months longer than that observed with paclitaxel administered every 3 weeks (14.2 vs. 10.3 months; hazard ratio, 0.62; 95% CI, 0.40 to 0.95; P = 0.03). However, among patients who received bevacizumab, weekly paclitaxel did not significantly prolong progression-free survival, as compared with paclitaxel administered every 3 weeks (14.9 months and 14.7 months, respectively; hazard ratio, 0.99; 95% CI, 0.83 to 1.20; P = 0.60). A test for interaction that assessed homogeneity of the treatment effect showed a significant difference between treatment with bevacizumab and without bevacizumab (P = 0.047). Patients who received weekly paclitaxel had a higher rate of grade 3 or 4 anemia than did those who received paclitaxel every 3 weeks (36% vs. 16%), as well as a higher rate of grade 2 to 4 sensory neuropathy (26% vs. 18%); however, they had a lower rate of grade 3 or 4 neutropenia (72% vs. 83%). CONCLUSIONS Overall, weekly paclitaxel, as compared with paclitaxel administered every 3 weeks, did not prolong progression-free survival among patients with ovarian cancer. (Funded by the National Cancer Institute and Genentech; GOG-0262 ClinicalTrials.gov number, NCT01167712.).

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