PURPOSE:Topotecan is an active second-line treatment for advanced ovarian cancer. Its efficacy as consolidation treatment after first-line standard chemotherapy is unknown. PATIENTS AND METHODS: To investigate whether topotecan (1.5 mg/m(2) on days 1 through 5, four cycles, every 3 weeks) prolonged progression-free survival (PFS) for patients responding to standard carboplatin (area under the curve 5) and paclitaxel (175 mg/m(2) administered as a 3-hour infusion in six cycles; CP), a multicenter phase III study was performed with an 80% power to detect a 50% prolongation of median PFS. Patients were registered at diagnosis and randomized after the end of CP. RESULTS:Two hundred seventy-three patients were randomly assigned (topotecan, n = 137; observation, n = 136), with a median age of 56 years. Stage at diagnosis was advanced in three fourths of patients (stage III in 65% of patients; stage IV in 10%); after primary surgery, 46% had no residual disease and 20% were optimally debulked. After CP, 87% reached a clinical complete response, and 13% achieved a partial response. Neutropenia (grade 3/4 in 58% of the patients) and thrombocytopenia (grade 3 in 21%; grade 4 in 3%) were the most frequent toxicities attributed to topotecan. There was no statistically significant difference in PFS between the arms (P =.83; log-rank test): median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm. Hazard ratio of progression for patients receiving topotecan was 1.18 (95% CI, 0.86 to 1.63) after adjustment for residual disease, interval debulking surgery, and response to CP. CONCLUSION: The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy withcarboplatin and paclitaxel.
RCT Entities:
PURPOSE:Topotecan is an active second-line treatment for advanced ovarian cancer. Its efficacy as consolidation treatment after first-line standard chemotherapy is unknown. PATIENTS AND METHODS: To investigate whether topotecan (1.5 mg/m(2) on days 1 through 5, four cycles, every 3 weeks) prolonged progression-free survival (PFS) for patients responding to standard carboplatin (area under the curve 5) and paclitaxel (175 mg/m(2) administered as a 3-hour infusion in six cycles; CP), a multicenter phase III study was performed with an 80% power to detect a 50% prolongation of median PFS. Patients were registered at diagnosis and randomized after the end of CP. RESULTS: Two hundred seventy-three patients were randomly assigned (topotecan, n = 137; observation, n = 136), with a median age of 56 years. Stage at diagnosis was advanced in three fourths of patients (stage III in 65% of patients; stage IV in 10%); after primary surgery, 46% had no residual disease and 20% were optimally debulked. After CP, 87% reached a clinical complete response, and 13% achieved a partial response. Neutropenia (grade 3/4 in 58% of the patients) and thrombocytopenia (grade 3 in 21%; grade 4 in 3%) were the most frequent toxicities attributed to topotecan. There was no statistically significant difference in PFS between the arms (P =.83; log-rank test): median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm. Hazard ratio of progression for patients receiving topotecan was 1.18 (95% CI, 0.86 to 1.63) after adjustment for residual disease, interval debulking surgery, and response to CP. CONCLUSION: The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel.
Authors: Lisa M Hess; Nan Rong; Patrick O Monahan; Paridha Gupta; Champ Thomaskutty; Daniela Matei Journal: Cancer Date: 2010-11-15 Impact factor: 6.860
Authors: Maurie Markman; P Y Liu; James Moon; Bradley J Monk; Larry Copeland; Sharon Wilczynski; David Alberts Journal: Gynecol Oncol Date: 2009-05-17 Impact factor: 5.482
Authors: Paul Sabbatini; Philipp Harter; Giovanni Scambia; Jalid Sehouli; Werner Meier; Pauline Wimberger; Klaus H Baumann; Christian Kurzeder; Barbara Schmalfeldt; David Cibula; Mariusz Bidzinski; Antonio Casado; Andrea Martoni; Nicoletta Colombo; Robert W Holloway; Luigi Selvaggi; Andrew Li; Jose del Campo; Karel Cwiertka; Tamas Pinter; Jan B Vermorken; Eric Pujade-Lauraine; Simona Scartoni; Monica Bertolotti; Cecilia Simonelli; Angela Capriati; Carlo Alberto Maggi; Jonathan S Berek; Jacobus Pfisterer Journal: J Clin Oncol Date: 2013-03-11 Impact factor: 44.544
Authors: Yong Soon Kwon; Joo-Hyun Nam; Dae-Yeon Kim; Dae-Shik Suh; Jong-Hyeok Kim; Yong Man Kim; Young Tak Kim Journal: J Korean Med Sci Date: 2009-07-30 Impact factor: 2.153