BEVACIZUMAB- CONTAINING FIRST LINE CHEMOTHERAPY MIGHT REDUCE PROGRESSION-FREE SURVIVAL AFTER RECURRENCE IN ADVANCED EPITHELIAL OVARIAN CANCER

Author(s):  
Tamar Perri
1999 ◽  
Vol 17 (7) ◽  
pp. 2069-2069 ◽  
Author(s):  
P. A. Vasey ◽  
J. Paul ◽  
A. Birt ◽  
E. J. Junor ◽  
N. S. Reed ◽  
...  

PURPOSE: A prospective, nonrandomized, multicenter, open feasibility study of cisplatin and docetaxel as first-line chemotherapy in International Federation of Gynecology and Obstetrics (FIGO) stage IC-IV epithelial ovarian cancer was conducted. The primary end point was the incidence of severe fluid retention that necessitated treatment withdrawal. PATIENTS AND METHODS: Cisplatin and docetaxel were administered every 3 weeks for six planned cycles, with a 5-day prophylactic dexamethasone regimen (8 mg two times per day). One hundred patients (median age, 53 years; range, 24 to 71 years) received a total of 512 cycles of chemotherapy in two cohorts: cohort 1, 49 patients, 258 cycles (cisplatin 75 mg/m2 and docetaxel 75 mg/m2); cohort 2, 51 patients, 254 cycles (cisplatin 75 mg/m2 and docetaxel 85 mg/m2). RESULTS: No patients were taken off study because of fluid retention. Sixty-six patients completed six cycles of protocol therapy; 16 stopped early because of toxicity (neurotoxicity in six patients, nephrotoxicity in three, neutropenia in two, and hypersensitivity, diarrhea and vomiting, skin rash, clinical deterioration, and patient's wishes in one patient each). Grade 3/4 neutropenia was observed in more than 75% of patients and seemed to be cumulative. Patients in cohort 2 had significantly more severe neutropenia and lethargy than those in cohort 1. In addition, there were five treatment-related deaths in cohort 2 (three neutropenia and two upper gastrointestinal hemorrhage). Neurotoxicity (mainly sensory, > grade 1) was observed in 23 patients. The overall clinical response rate was 69% (complete response, 38%; partial response, 31%); CA-125 response rate was 73%. Median progression-free survival for the group was 12 months. CONCLUSION: Cisplatin and docetaxel can be administered at doses of 75 mg/m2 and 75 mg/m2, respectively, every 3 weeks, and the utility of this regimen is not limited by fluid retention. However, 33 of 100 patients were unable to complete the planned six cycles, which may explain, in part, the poor overall progression-free survival. Increasing the docetaxel dose to 85 mg/m2 adds unacceptable hematologic toxicity and potential risks to the patient.


2014 ◽  
Vol 32 (30) ◽  
pp. 3374-3382 ◽  
Author(s):  
Andreas du Bois ◽  
Anne Floquet ◽  
Jae-Weon Kim ◽  
Joern Rau ◽  
Josep M. del Campo ◽  
...  

PurposePazopanib is an oral, multikinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -1/-2/-3, platelet-derived growth factor receptor (PDGFR) -α/-β, and c-Kit. Preclinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment. This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy.Patients and MethodsNine hundred forty patients with histologically confirmed cancer of the ovary, fallopian tube, or peritoneum, International Federation Gynecology Obstetrics (FIGO) stages II-IV, no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy were randomized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months. The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators.ResultsMaintenance pazopanib prolonged progression-free survival compared with placebo (hazard ratio [HR], 0.77; 95% CI, 0.64 to 0.91; P = .0021; median, 17.9 v 12.3 months, respectively). Interim survival analysis based on events in 35.6% of the population did not show any significant difference. Grade 3 or 4 adverse events of hypertension (30.8%), neutropenia (9.9%), liver-related toxicity (9.4%), diarrhea (8.2%), fatigue (2.7%), thrombocytopenia (2.5%), and palmar-plantar erythrodysesthesia (1.9%) were significantly higher in the pazopanib arm. Treatment discontinuation related to adverse events was higher among patients treated with pazopanib (33.3%) compared with placebo (5.6%).ConclusionPazopanib maintenance therapy provided a median improvement of 5.6 months (HR, 0.77) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy. Overall survival data to this point did not suggest any benefit. Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity (NCT00866697).


2009 ◽  
Vol 27 (28) ◽  
pp. 4642-4648 ◽  
Author(s):  
Sergio Pecorelli ◽  
Giuseppe Favalli ◽  
Angiolo Gadducci ◽  
Dionyssios Katsaros ◽  
Pierluigi Benedetti Panici ◽  
...  

Purpose To assess whether six courses of paclitaxel are effective as consolidation treatment in patients with advanced epithelial ovarian cancer who are in complete response after first-line paclitaxel/platinum–based chemotherapy. Patients and Methods Patients with stages IIb to IV disease in clinical or pathologic complete response after six courses of paclitaxel/platinum–based chemotherapy were randomly allocated to either observation (ie, control) or six courses of paclitaxel 175 mg/m2 every 3 weeks (ie, maintenance). Results Two hundred patients were randomly assigned from March 1999 to July 2006. Because of the low accrual rate, an unplanned interim analysis of futility according to the Bayesian approach was performed. Grade 2 or greater motor neurotoxicity and sensory neurotoxicity were reported in 11.3% and 28.0% of the paclitaxel-arm patients, respectively. After a median follow-up of 43.5 months, 107 patients (53%) had experienced relapse, and 48 patients (24%) had died. Two-year progression-free survival rates were 54% (95% CI, 43% to 64%) and 59% (95% CI, 49% to 69%; P = not significant) in the control and maintenance arms, respectively. Corresponding 2-year overall survival rates were 90% (95% CI, 84% to 97%) and 87% (95% CI, 80% to 94%; P = not significant), respectively. The Cox model showed that residual disease after initial surgery (macroscopic v no macroscopic residuum; hazard ratio [HR], 1.91; 95%CI, 1.21 to 3.03) and stage (IIIc to IV v others; HR, 3.10; 95% CI, 1.13 to 8.48) were independent prognostic factors for progression-free survival, whereas the treatment arm (maintenance v control) had no prognostic relevance. Conclusion A consolidation treatment with six cycles of paclitaxel does not prolong progression-free survival or overall survival in patients in complete response after first-line paclitaxel/platinum–based regimens.


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