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N Engl J Med. 2016 Feb 25;374(8):738-48. doi: 10.1056/NEJMoa1505067.

Weekly vs. Every-3-Week Paclitaxel and Carboplatin for Ovarian Cancer.

Author information

1
From the California Pacific-Palo Alto Medical Foundation, Sutter Cancer Research Institute, San Francisco (J.K.C.); NRG Oncology-Gynecologic Oncology Group Statistics and Data Center, Roswell Park Cancer Institute, Buffalo, NY (M.F.B., H.H.); Massachusetts General Hospital, Boston (R.T.P., M.J.B.); University of Oklahoma, Oklahoma City (J.L.W.); Women and Infants Hospital, Providence, RI (P.A.D.S.); University of Pennsylvania (S.C.R.) and Fox Chase Cancer Center (L.P.M.) - both in Philadelphia; University of Colorado Cancer Center, Aurora (S.A.D.); University of Alabama at Birmingham, Birmingham (W.K.H.); James Cancer Center, Ohio State University, Columbus (D.M.O.); Minnesota Oncology/Hematology-Oncology Service, Edina (M.P.B.); Indiana University School of Medicine, Carmel (H.M.); and University of Arizona Cancer Center, Creighton University School of Medicine, and St. Joseph's Hospital and Medical Center (B.J.M.) - all in Phoenix.

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 progression-free 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.).

PMID:
26933849
PMCID:
PMC5081077
DOI:
10.1056/NEJMoa1505067
[Indexed for MEDLINE]
Free PMC Article

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