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.)

ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease

“…When patients did not receive bevacizumab, a subgroup analysis of the GOG 262 trial showed a significant increase in PFS in favour of weekly paclitaxel compared with 3-weekly. When receiving bevacizumab, no differences in PFS were shown 199. As this subgroup analysis was not pre-planned and only performed on 16% of the study population, weekly paclitaxel should not be regarded as a substitution for bevacizumab.…”

FIGO stage IV epithelial ovarian, fallopian tube and peritoneal cancer revisited

“…In subgroup analysis the OS benefit was not seen for stage IV patients (dose dense 36 months versus conventional 33 months, p = 0.76). Further, dose-dense weekly paclitaxel studies (GOG #262 [76] and MITO-7 [77]) could also not demonstrate a significant benefit for the dose-dense regimens. There is no robust clinical data on efficacy of intra-peritoneal (IP) therapy in stage IV patients.…”

Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies

“…As noted above, these post hoc results must be interpreted with caution, and larger prospective studies are needed. 1 found a marginal benefit of dose-dense (weekly) chemotherapy over standard chemotherapy in a group of 112 women with ovarian cancer who did not receive bevacizumab, a subgroup that represents a mere 16% of the whole. The use of progressionfree survival, instead of overall survival, in trials of ovarian-cancer therapies will exaggerate the benefit of a therapy that delays progression but has no effect on survival.…”

“…In our recent analysis of data from a large administrative U.S. database (the Healthcare Cost and Utilization Project National Inpatient Sample), we found remarkable similarity between patients with dilated cardiomyopathy and those with peripartum cardiomyopathy in terms of demographic and clinical characteristics and patient outcomes in pregnancy during the hospitalization for delivery. 1 Approximately 30% of the women in each cohort were black, and the two cohorts had similarly elevated rates of death, heart failure, arrhythmias, and preeclampsia spectrum disorders. Perhaps some of the patients (mis)classified as having peripartum cardiomyopathy were women with an asymptomatic dilated cardiomyopathy before pregnancy, and the hemodynamic demands of pregnancy worsened the degree of left ventricular dysfunction, leading to clinical heart failure.…”

“…To the Editor: Ware et al (Jan. 21 issue) 1 describe a very similar distribution of presumably causative genetic variants in TTN and other genes in women with peripartum cardiomyopathy and in persons with idiopathic dilated cardiomyopathy. The clinical outcome of peripartum cardiomyopathy is highly variable, ranging from full recovery to rapid progression to end-stage heart failure, 2 …”