Incorporating bevacizumab in a chemotherapy regimen (7.5 mg/kg every 3 weeks for five or six cycles) and then continuing bevacizumab alone for a total of 12 months of treatment extended ...progression-free survival in advanced and high-risk early-stage ovarian cancer.
Epithelial ovarian cancer and related cancers lead to 15,000 deaths in the United States annually, representing the fifth leading cause of death from cancer among women.
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The poor prognosis is usually attributed to advanced stage at diagnosis and inadequate chemotherapy.
Vascular endothelial growth factor (VEGF) and angiogenesis are important promoters of ovarian-cancer progression.
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Both correlate directly with the extent of disease and inversely with progression-free survival
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and overall survival,
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often independently of known prognostic factors.
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Bevacizumab, a humanized VEGF-neutralizing monoclonal antibody, inhibits tumor angiogenesis
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and has shown single-agent activity in phase 2 epithelial . . .
Vascular endothelial growth factor (VEGF) seems to be a promoter of tumor progression for epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC). We conducted a phase II trial to assess ...the efficacy and tolerability of single-agent bevacizumab, an anti-VEGF monoclonal antibody.
Eligible patients had persistent or recurrent EOC/PPC after one to two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group performance status of at least 2. Treatment consisted of bevacizumab 15 mg/kg intravenously every 21 days until disease progression or prohibitive toxicity. Primary end points were progression-free survival (PFS) at 6 months and clinical response.
The study consisted of 62 eligible and assessable patients, median age 57 years, 41 (66.1%) having received two prior regimens and 36 (58.1%) CORRECTED considered platinum resistant. Grade 3 adverse events at least possibly related to bevacizumab were hematologic (1), GI (3), hypertension (6), thromboembolism (1), allergy (2), hepatic (1), pain (3), coagulation (1), constitutional (1), and dyspnea (1). Grade 4 adverse events included pulmonary embolus (1), vomiting and constipation (1), and proteinuria (1). Thirteen patients (21.0%) experienced clinical responses (two complete, 11 partial; median response duration, 10 months), and 25 (40.3%) survived progression free for at least 6 months. Median PFS and overall survival were 4.7 and 17 months, respectively. There was no significant association of prior platinum sensitivity, age, number of prior chemotherapeutic regimens, or performance status with the hazard of progression or death.
Bevacizumab seems to be well tolerated and active in the second- and third-line treatment of patients with EOC/PPC and merits phase III investigation.
In randomized trials the combination of cisplatin and paclitaxel was superior to cisplatin and cyclophosphamide in advanced-stage epithelial ovarian cancer. Although in nonrandomized trials, ...carboplatin and paclitaxel was a less toxic and highly active combination regimen, there remained concern regarding its efficacy in patients with small-volume, resected, stage III disease. Thus, we conducted a noninferiority trial of cisplatin and paclitaxel versus carboplatin and paclitaxel in this population.
Patients with advanced ovarian cancer and no residual mass greater than 1.0 cm after surgery were randomly assigned to receive cisplatin 75 mg/m2 plus a 24-hour infusion of paclitaxel 135 mg/m2 (arm I), or carboplatin area under the curve 7.5 intravenously plus paclitaxel 175 mg/m2 over 3 hours (arm II).
Seven hundred ninety-two eligible patients were enrolled onto the study. Prognostic factors were similar in the two treatment groups. Gastrointestinal, renal, and metabolic toxicity, as well as grade 4 leukopenia, were significantly more frequent in arm I. Grade 2 or greater thrombocytopenia was more common in arm II. Neurologic toxicity was similar in both regimens. Median progression-free survival and overall survival were 19.4 and 48.7 months, respectively, for arm I compared with 20.7 and 57.4 months, respectively, for arm II. The relative risk (RR) of progression for the carboplatin plus paclitaxel group was 0.88 (95% confidence interval CI, 0.75 to 1.03) and the RR of death was 0.84 (95% CI, 0.70 to 1.02).
In patients with advanced ovarian cancer, a chemotherapy regimen consisting of carboplatin plus paclitaxel results in less toxicity, is easier to administer, and is not inferior, when compared with cisplatin plus paclitaxel.
Abstract Objectives Predictive factors for efficacy of bevacizumab in advanced ovarian cancer have remained elusive. We investigated ascites both as a prognostic factor and as a predictor of efficacy ...for bevacizumab. Methods Using data from GOG 0218, patients receiving cytotoxic therapy plus concurrent and maintenance bevacizumab were compared to those receiving cytotoxic therapy plus placebo. The presence of ascites was determined prospectively. Chi-square and Wilcoxon–Mann–Whitney tests compared baseline variables between subgroups. Survival was estimated by Kaplan–Meier method, and Cox proportional hazard models were used to evaluate independent prognostic factors and estimate their covariate-adjusted effects on survival. Results Treatment arms were balanced with respect to ascites and other prognostic factors. Overall, 886 (80%) women had ascites, 221 (20%) did not. Those with ascites were more likely to have: poorer performance status (p < 0.001); serous histology (p = 0.012); higher baseline CA125 (p < 0.001); and suboptimal cytoreduction (p = 0.004). In multivariate survival analysis, ascites was prognostic of poor OS (Adjusted HR 1.22, 95% CI 1.00–1.48, p = 0.045), but not PFS. In predictive analysis, patients without ascites treated with bevacizumab had no significant improvement in either PFS (AHR 0.81, 95% CI 0.59–1.10, p = 0.18) or OS (AHR 0.94, 95% CI 0.65–1.36, p = 0.76). Patients with ascites treated with bevacizumab had significantly improved PFS (AHR 0.71, 95% CI 0.62–0.81, p < 0.001) and OS (AHR 0.82, 95% CI 0.70–0.96, p = 0.014). Conclusions Ascites in women with advanced ovarian cancer is prognostic of poor overall survival. Ascites may predict the population of women more likely to derive long-term benefit from bevacizumab.
To evaluate risk factors for GI adverse events (AEs) within a phase III trial of bevacizumab in first-line ovarian cancer therapy.
Women with previously untreated advanced disease after surgery were ...randomly allocated to six cycles of platinum-taxane chemotherapy plus placebo cycles (C)2 to C22 (R1); chemotherapy plus bevacizumab C2 to C6 plus placebo C7 to C22 (R2); or chemotherapy plus bevacizumab C2 to C22 (R3). Patients were evaluated for history or on-study development of potential risk factors for GI AEs defined as grade ≥ 2 perforation, fistula, necrosis, or hemorrhage.
Of 1,873 patients enrolled, 1,759 (94%) were evaluable, and 2.8% (50 of 1,759) experienced a GI AE: 10 of 587 (1.7%, R1), 20 of 587 (3.4%, R2), and 20 of 585 (3.4%, R3). Univariable analyses indicated that previous treatment of inflammatory bowel disease (IBD; P = .005) and small bowel resection (SBR; P = .032) or large bowel resection (LBR; P = .012) at primary surgery were significantly associated with a GI AE. The multivariable estimated relative odds of a GI AE were 13.4 (95% CI, 3.44 to 52.3; P < .001) for IBD; 2.05 (95% CI, 1.09 to 3.88; P = .026) for LBR; 1.95 (95% CI, 0.894 to 4.25; P = .093) for SBR; and 2.15 for bevacizumab exposure (aggregated 95% CI, 1.05 to 4.40; P = .036).
History of treatment for IBD, and bowel resection at primary surgery, increase the odds of GI AEs in patients receiving first-line platinum-taxane chemotherapy for advanced ovarian cancer. After accounting for these risk factors, concurrent bevacizumab doubles the odds of a GI AE, but is not appreciably increased by continuation beyond chemotherapy.
Purpose: In randomized trials the combination of cisplatin and paclitaxel was superior to cisplatin and cyclophosphamide in advanced-stage epithelial ovarian cancer. Although in nonrandomized trials, ...carboplatin and paclitaxel was a less toxic and highly active combination regimen, there remained concern regarding its efficacy in patients with small-volume, resected, stage III disease. Thus, we conducted a noninferiority trial of cisplatin and paclitaxel versus carboplatin and paclitaxel in this population.
Patients and Methods: Patients with advanced ovarian cancer and no residual mass greater than 1.0 cm after surgery were randomly assigned to receive cisplatin 75 mg/m
2
plus a 24-hour infusion of paclitaxel 135 mg/m
2
(arm I), or carboplatin area under the curve 7.5 intravenously plus paclitaxel 175 mg/m
2
over 3 hours (arm II).
Results: Seven hundred ninety-two eligible patients were enrolled onto the study. Prognostic factors were similar in the two treatment groups. Gastrointestinal, renal, and metabolic toxicity, as well as grade 4 leukopenia, were significantly more frequent in arm I. Grade 2 or greater thrombocytopenia was more common in arm II. Neurologic toxicity was similar in both regimens. Median progression-free survival and overall survival were 19.4 and 48.7 months, respectively, for arm I compared with 20.7 and 57.4 months, respectively, for arm II. The relative risk (RR) of progression for the carboplatin plus paclitaxel group was 0.88 (95% confidence interval CI, 0.75 to 1.03) and the RR of death was 0.84 (95% CI, 0.70 to 1.02).
Conclusion: In patients with advanced ovarian cancer, a chemotherapy regimen consisting of carboplatin plus paclitaxel results in less toxicity, is easier to administer, and is not inferior, when compared with cisplatin plus paclitaxel.
More than 14 million new cancer cases and 8.2 million cancer deaths are estimated to occur worldwide on an annual basis. Of these, 57% of new cancer cases and 65% of cancer deaths occur in low- and ...middle-income countries. Disparities in available resources for health care are enormous and staggering. The WHO estimates that the United States and Canada have 10% of the global burden of disease, 37% of the world's health workers, and more than 50% of the world's financial resources for health; by contrast, the African region has 24% of the global burden of disease, 3% of health workers, and less than 1% of the world's financial resources for health. This disparity is even more extreme with cancer. NCCN has developed a framework for stratifying the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) to help health care systems in providing optimal care for patients with cancer with varying available resources. This framework is modified from a method developed by the Breast Health Global Initiative. The NCCN Framework for Resource Stratification (NCCN Framework) identifies 4 resource environments: basic resources, core resources, enhanced resources, and NCCN Guidelines, and presents the recommendations in a graphic format that always maintains the context of the NCCN Guidelines. This article describes the rationale for resource-stratified guidelines and the methodology for developing the NCCN Framework, using a portion of the NCCN Cervical Cancer Guideline as an example.
Abstract Purpose To analyze quality of life (QOL) in a randomized, placebo-controlled phase III trial concluding that the addition of concurrent and maintenance bevacizumab (Arm 3) to carboplatin and ...paclitaxel prolongs progression-free survival in front-line treatment of advanced ovarian cancer compared to chemotherapy alone (Arm 1) or chemotherapy with bevacizumab in cycles 2–6 only (Arm 2). Patients and methods The Trial Outcome Index of the Functional Assessment of Cancer Therapy-Ovary (FACT-O TOI) was used to assess QOL before cycles 1, 4, 7, 13, and 21; and 6 months after completing study therapy. Differences in QOL scores were assessed using a linear mixed model, adjusting for baseline score, and age. The significance level was set at 0.0167 to account for multiple comparisons. Results 1693 patients were queried. Arm 2 (p < 0.001) and Arm 3 (p < 0.001) reported lower QOL scores than those in Arm 1. The treatment differences were observed mainly at cycle 4, when the patients receiving bevacizumab (Arm 2 and Arm 3) reported 2.72 points (98.3% CI: 0.88–4.57; effect size = 0.18) and 2.96 points (98.3% CI: 1.13–4.78; effect size = 0.20) lower QOL respectively, than those in Arm 1. The difference in QOL scores between Arm 1 and Arm 3 remained statistically significant up to cycle 7. The percentage of patients who reported abdominal discomfort dropped over time, without significant differences among study arms. Conclusion The small QOL difference observed during chemotherapy did not persist during maintenance bevacizumab.
New NCCN Guidelines for Vulvar Cancer Greer, Benjamin E; Koh, Wui-Jin
Journal of the National Comprehensive Cancer Network,
05/2016, Letnik:
14, Številka:
5 Suppl
Journal Article
Recenzirano
For the first time, NCCN Guidelines are available for vulvar cancer, a rare gynecologic cancer. Early-stage cancers can be managed by surgery and observation, and many of these patients can be cured. ...Lymph node status drives treatment and correlates with survival. Positive groinal nodes require additional therapy, including radiation plus chemotherapy, depending on stage. Sentinel lymph node biopsy is recommended in selected patients.
A phase 2 trial was conducted to determine the toxicity and efficacy of combined weekly topotecan and biweekly bevacizumab in patients with primary or secondary platinum-resistant ovarian, ...peritoneal, or fallopian tube cancer (OC).
Patients were treated with bevacizumab 10 mg/kg on days 1 and 15 and topotecan 4 mg/m(2) on days 1, 8, and 15 of a 28-day cycle until progressive disease (PD) or excessive toxicity. The primary endpoint was progression-free survival (PFS); secondary objectives included overall survival (OS), objective response, and toxicity.
Patients (N = 40) received a median of 8 treatment cycles. Toxicity was generally mild or moderate, with neutropenia (18%), hypertension (20%), gastrointestinal toxicity (18%), pain (13%), metabolic toxicity (15%), bowel obstruction (10%), and cardiotoxicity (8%) being the most common grade 3 and 4 adverse events. No bowel perforations, febrile neutropenia, or treatment-related deaths occurred. Median PFS and OS were 7.8 (95% confidence interval CI, 3.0-9.4) and 16.6 months (95% CI, 12.8-22.9), with 22 (55%) patients progression-free for ≥6 months. Ten (25%) patients had partial response (PR), 14 (35%) had stable disease (SD), and 16 (40%) had PD. Patients treated with 2 prior regimens received greater benefit than patients treated with 1: PR/SD, 78.9% versus 42.9% (P = .03); median PFS, 10.9 versus 2.8 months (P = .08); median OS, 22.9 versus 12.8 months (P = .02).
A weekly topotecan and biweekly bevacizumab combination demonstrates acceptable toxicity and encouraging efficacy in patients with platinum-resistant OC; further study is warranted.
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