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 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.).
authors.affiliation: 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.
authors.forename: John K
authors.initials: JK
authors.lastname: Chan
authors.affiliation: 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.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Brady
authors.affiliation: 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.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Penson
authors.affiliation: 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.
authors.forename: Helen
authors.initials: H
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Birrer
authors.affiliation: 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.
authors.forename: Joan L
authors.initials: JL
authors.lastname: Walker
authors.affiliation: 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.
authors.forename: Paul A
authors.initials: PA
authors.lastname: DiSilvestro
authors.affiliation: 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.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Rubin
authors.affiliation: 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.
authors.forename: Lainie P
authors.initials: LP
authors.lastname: Martin
authors.affiliation: 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.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Davidson
authors.affiliation: 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.
authors.forename: Warner K
authors.initials: WK
authors.lastname: Huh
authors.affiliation: 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.
authors.forename: David M
authors.initials: DM
authors.lastname: O'Malley
authors.affiliation: 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.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Boente
authors.affiliation: 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.
authors.forename: Helen
authors.initials: H
authors.lastname: Michael
authors.affiliation: 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.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D057194:Intention to Treat Analysis; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage*
chemical_list: D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel