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1.
J Clin Oncol ; 41(25): 4077-4083, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37643542

ABSTRACT

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/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).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.

2.
J Emerg Manag ; 20(7): 29-38, 2021.
Article in English | MEDLINE | ID: mdl-35412642

ABSTRACT

A functional mutual aid system allows the effective cost sharing of resources and the swift mitigation of loss of life and property. COVID-19 has illuminated weaknesses in our mutual aid framework. Weaknesses could potentially allow abuse and the misuse of these unifying instruments. By designing our response system in an insightful and nuanced fashion, we are able to affectively lend aid to those in need. Our mutual aid systems allow us to be forward thinking-it -challenges us to anticipate what could happen and how we should respond. This article will articulate challenges COVID-19 has posed in our mutual aid system and will propose potential improvements to better enhance our aid agreements for future pandemics.


Subject(s)
COVID-19 , COVID-19/epidemiology , Forecasting , Humans , Pandemics , SARS-CoV-2
3.
J Clin Oncol ; 37(26): 2317-2328, 2019 09 10.
Article in English | MEDLINE | ID: mdl-31216226

ABSTRACT

PURPOSE: We report the final, protocol-specified analysis of overall survival (OS) in GOG-0218, a phase III, randomized trial of bevacizumab in women with newly diagnosed ovarian, fallopian tube, or primary peritoneal carcinoma. METHODS: A total of 1,873 women with incompletely resected stage III to IV disease were randomly assigned 1:1:1 to six 21-day cycles of intravenous carboplatin (area under the concentration v time curve 6) and paclitaxel (175 mg/m2) versus chemotherapy plus concurrent bevacizumab (15 mg/kg, cycles 2 to 6) versus chemotherapy plus concurrent and maintenance bevacizumab (cycles 2 to 22). Inclusion criteria included a Gynecologic Oncology Group performance status of 0 to 2 and no history of clinically significant vascular events or evidence of intestinal obstruction. OS was analyzed in the intention-to-treat population. A total of 1,195 serum and/or tumor specimens were sequenced for BRCA1/2 and damaging mutations in homologous recombination repair (HRR) genes. Intratumoral microvessel density was studied using CD31 immunohistochemistry. RESULTS: Median follow-up was 102.9 months. Relative to control (n = 625), for patients receiving bevacizumab-concurrent (n = 625), the hazard ratio (HR) of death was 1.06 (95% CI, 0.94 to 1.20); for bevacizumab-concurrent plus maintenance (n = 623), the HR was 0.96 (95% CI, 0.85 to 1.09). Disease-specific survival was not improved in any arm. No survival advantage was observed after censoring patients who received bevacizumab at crossover or as second line. Median OS for stage IV bevacizumab-concurrent plus maintenance was 42.8 v 32.6 months for stage IV control (HR, 0.75; 95% CI, 0.59 to 0.95). Relative to wild type, the HR for death for BRCA1/2 mutated carcinomas was 0.62 (95% CI, 0.52 to 0.73), and for non-BRCA1/2 HRR, the HR was 0.65 (95% CI, 0.51 to 0.85). BRCA1/2, HRR, and CD31 were not predictive of bevacizumab activity. CONCLUSION: No survival differences were observed for patients who received bevacizumab compared with chemotherapy alone. Testing for BRCA1/2 mutations and homologous recombination deficiency is essential.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Ovarian Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carcinoma, Ovarian Epithelial/mortality , Double-Blind Method , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Ovarian Neoplasms/mortality , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Young Adult
4.
J Natl Compr Canc Netw ; 15(1): 92-120, 2017 01.
Article in English | MEDLINE | ID: mdl-28040721

ABSTRACT

Vulvar cancer is a rare gynecologic malignancy. Ninety percent of vulvar cancers are predominantly squamous cell carcinomas (SCCs), which can arise through human papilloma virus (HPV)-dependent and HPV-independent pathways. The NCCN Vulvar Cancer panel is an interdisciplinary group of representatives from NCCN Member Institutions consisting of specialists in gynecological oncology, medical oncology, radiation oncology, and pathology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vulvar Cancer provide an evidence- and consensus-based approach for the management of patients with vulvar SCC. This manuscript discusses the recommendations outlined in the NCCN Guidelines for diagnosis, staging, treatment, and follow-up.


Subject(s)
Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/therapy , Neoplasm Recurrence, Local/diagnosis , Papillomavirus Infections/diagnosis , Papillomavirus Infections/therapy , Vulvar Neoplasms/diagnosis , Vulvar Neoplasms/therapy , Antineoplastic Agents/therapeutic use , Biopsy , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/pathology , Chemoradiotherapy , Female , Humans , Medical Oncology/standards , Neoplasm Recurrence, Local/therapy , Neoplasm Staging , Papillomavirus Infections/epidemiology , Papillomavirus Infections/pathology , Radiotherapy, Adjuvant , Risk Factors , Survival Rate , Vulvar Neoplasms/epidemiology , Vulvar Neoplasms/pathology
5.
J Natl Compr Canc Netw ; 14(8): 961-9, 2016 08.
Article in English | MEDLINE | ID: mdl-27496112

ABSTRACT

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.


Subject(s)
Delivery of Health Care/standards , Global Health/standards , Health Resources , Medical Oncology/standards , Quality of Health Care , Female , Humans , Male , Practice Guidelines as Topic , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/therapy
6.
J Natl Compr Canc Netw ; 14(5 Suppl): 656-8, 2016 05.
Article in English | MEDLINE | ID: mdl-27226506

ABSTRACT

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.


Subject(s)
Vulvar Neoplasms/surgery , Vulvar Neoplasms/therapy , Female , Humans , Vulvar Neoplasms/pathology
7.
J Natl Compr Canc Netw ; 13(11): 1321-31, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26553763

ABSTRACT

The NCCN Guidelines for Uterine Neoplasms provide interdisciplinary recommendations for treating endometrial carcinoma and uterine sarcomas. These NCCN Guidelines Insights summarize the NCCN Uterine Neoplasms Panel's 2016 discussions and major guideline updates for treating uterine sarcomas. During this most recent update, the panel updated the mesenchymal tumor classification to correspond with recent updates to the WHO tumor classification system. Additionally, the panel revised its systemic therapy recommendations to reflect new data and collective clinical experience. These NCCN Guidelines Insights elaborate on the rationale behind these recent changes.


Subject(s)
Sarcoma/diagnosis , Sarcoma/therapy , Uterine Neoplasms/diagnosis , Uterine Neoplasms/therapy , Female , Humans , Neoplasm Grading , Prognosis , Sarcoma/etiology , Sarcoma/mortality , Uterine Neoplasms/etiology , Uterine Neoplasms/mortality
8.
Gynecol Oncol ; 139(1): 17-22, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26216729

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ascites/pathology , Fallopian Tube Neoplasms/drug therapy , Neoplasms, Glandular and Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Peritoneal Neoplasms/drug therapy , Bevacizumab/administration & dosage , Carcinoma, Ovarian Epithelial , Fallopian Tube Neoplasms/pathology , Fallopian Tube Neoplasms/surgery , Female , Humans , Middle Aged , Neoplasms, Glandular and Epithelial/pathology , Neoplasms, Glandular and Epithelial/surgery , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/surgery , Predictive Value of Tests , Prognosis
9.
J Natl Compr Canc Netw ; 13(4): 395-404; quiz 404, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25870376

ABSTRACT

The NCCN Guidelines for Cervical Cancer provide interdisciplinary recommendations for treating cervical cancer. These NCCN Guidelines Insights summarize the NCCN Cervical Cancer Panel's discussion and major guideline updates from 2014 and 2015. The recommended systemic therapy options for recurrent and metastatic cervical cancer were amended upon panel review of new survival data and the FDA's approval of bevacizumab for treating late-stage cervical cancer. This article outlines relevant data and provides insight into panel decisions regarding various combination regimens. Additionally, a new section was added to provide additional guidance on key principles of evaluation and surgical staging in cervical cancer. This article highlights 2 areas of active investigation and debate from this new section: sentinel lymph node mapping and fertility-sparing treatment approaches.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Practice Guidelines as Topic , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/pathology , Female , Fertility Preservation , Humans , Neoplasm Staging , Uterine Cervical Neoplasms/surgery
10.
J Natl Compr Canc Netw ; 12(2): 248-80, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24586086

ABSTRACT

Adenocarcinoma of the endometrium (also known as endometrial cancer or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. An estimated 49,560 new uterine cancer cases will occur in 2013, with 8190 deaths resulting from the disease. Uterine sarcomas (stromal/mesenchymal tumors) are uncommon malignancies, accounting for approximately 3% of all uterine cancers. The NCCN Guidelines for Uterine Neoplasms describe malignant epithelial carcinomas and uterine sarcomas; each of these major categories contains specific histologic groups that require different management. This excerpt of these guidelines focuses on early-stage disease.


Subject(s)
Uterine Neoplasms/diagnosis , Uterine Neoplasms/therapy , Female , Humans
11.
J Clin Oncol ; 32(12): 1210-7, 2014 Apr 20.
Article in English | MEDLINE | ID: mdl-24637999

ABSTRACT

PURPOSE: To evaluate risk factors for GI adverse events (AEs) within a phase III trial of bevacizumab in first-line ovarian cancer therapy. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Gastrointestinal Diseases/chemically induced , Ovarian Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab , Disease-Free Survival , Double-Blind Method , Female , Gastrointestinal Diseases/drug therapy , Humans , Logistic Models , Middle Aged , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Ovarian Neoplasms/pathology , Risk Factors , Taxoids/administration & dosage , Young Adult
12.
J Natl Compr Canc Netw ; 11(3): 320-43, 2013 Mar 01.
Article in English | MEDLINE | ID: mdl-23486458

ABSTRACT

These NCCN Clinical Practice Guidelines in Oncology for Cervical Cancer focus on early-stage disease, because it occurs more frequently in the United States. After careful clinical evaluation and staging, the primary treatment of early-stage cervical cancer is either surgery or radiotherapy. These guidelines include fertility-sparing and non-fertility-sparing treatment for those with early-stage disease, which is disease confined to the uterus. A new fertility-sparing algorithm was added for select patients with stage IA and IB1 disease..


Subject(s)
Uterine Cervical Neoplasms/therapy , Chemoradiotherapy, Adjuvant , Combined Modality Therapy , Disease Management , Female , Humans , Hysterectomy , Neoplasm Staging , Radiotherapy Planning, Computer-Assisted , Randomized Controlled Trials as Topic , Uterine Cervical Neoplasms/pathology
13.
Gynecol Oncol ; 128(3): 573-8, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23219660

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 6months 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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ovarian Neoplasms/drug therapy , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab , Carboplatin/administration & dosage , Carboplatin/adverse effects , Disease-Free Survival , Female , Humans , Maintenance Chemotherapy , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Placebos , Quality of Life , Treatment Outcome
14.
Magn Reson Imaging ; 30(9): 1291-300, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22795929

ABSTRACT

The Seattle Cancer Care Alliance (SCCA) is a Pacific Northwest regional network that enables patients from community cancer centers to participate in multicenter oncology clinical trials where patients can receive some trial-related procedures at their local center. Results of positron emission tomography (PET) scans performed at community cancer centers are not currently used in SCCA Network trials since clinical trials customarily accept results from only trial-accredited PET imaging centers located at academic and large hospitals. Oncologists would prefer the option of using standard clinical PET scans from Network sites in multicenter clinical trials to increase accrual of patients for whom additional travel requirements for imaging are a barrier to recruitment. In an effort to increase accrual of rural and other underserved populations to Network trials, researchers and clinicians at the University of Washington, SCCA and its Network are assessing the feasibility of using PET scans from all Network sites in their oncology clinical trials. A feasibility study is required because the reproducibility of multicenter PET measurements ranges from approximately 3% to 40% at national academic centers. Early experiences from both national and local PET phantom imaging trials are discussed, and next steps are proposed for including patient PET scans from the emerging regional quantitative imaging network in clinical trials. There are feasible methods to determine and characterize PET quantitation errors and improve data quality by either prospective scanner calibration or retrospective post hoc corrections. These methods should be developed and implemented in multicenter clinical trials employing quantitative PET imaging of patients.


Subject(s)
Clinical Trials as Topic , Neoplasms/therapy , Positron-Emission Tomography/methods , Tomography, X-Ray Computed/methods , Calibration , Cancer Care Facilities , Diagnostic Imaging/methods , Humans , Medical Oncology/methods , Medically Underserved Area , Multicenter Studies as Topic , Phantoms, Imaging , Reproducibility of Results , Research Design , Rural Population , Universities , Washington
15.
N Engl J Med ; 365(26): 2473-83, 2011 Dec 29.
Article in English | MEDLINE | ID: mdl-22204724

ABSTRACT

BACKGROUND: Vascular endothelial growth factor is a key promoter of angiogenesis and disease progression in epithelial ovarian cancer. Bevacizumab, a humanized anti-vascular endothelial growth factor monoclonal antibody, has shown single-agent activity in women with recurrent tumors. Thus, we aimed to evaluate the addition of bevacizumab to standard front-line therapy. METHODS: In our double-blind, placebo-controlled, phase 3 trial, we randomly assigned eligible patients with newly diagnosed stage III (incompletely resectable) or stage IV epithelial ovarian cancer who had undergone debulking surgery to receive one of three treatments. All three included chemotherapy consisting of intravenous paclitaxel at a dose of 175 mg per square meter of body-surface area, plus carboplatin at an area under the curve of 6, for cycles 1 through 6, plus a study treatment for cycles 2 through 22, each cycle of 3 weeks' duration. The control treatment was chemotherapy with placebo added in cycles 2 through 22; bevacizumab-initiation treatment was chemotherapy with bevacizumab (15 mg per kilogram of body weight) added in cycles 2 through 6 and placebo added in cycles 7 through 22. Bevacizumab-throughout treatment was chemotherapy with bevacizumab added in cycles 2 through 22. The primary end point was progression-free survival. RESULTS: Overall, 1873 women were enrolled. The median progression-free survival was 10.3 months in the control group, 11.2 in the bevacizumab-initiation group, and 14.1 in the bevacizumab-throughout group. Relative to control treatment, the hazard ratio for progression or death was 0.908 (95% confidence interval [CI], 0.795 to 1.040; P=0.16) with bevacizumab initiation and 0.717 (95% CI, 0.625 to 0.824; P<0.001) with bevacizumab throughout. At the time of analysis, 76.3% of patients were alive, with no significant differences in overall survival among the three groups. The rate of hypertension requiring medical therapy was higher in the bevacizumab-initiation group (16.5%) and the bevacizumab-throughout group (22.9%) than in the control group (7.2%). Gastrointestinal-wall disruption requiring medical intervention occurred in 1.2%, 2.8%, and 2.6% of patients in the control group, the bevacizumab-initiation group, and the bevacizumab-throughout group, respectively. CONCLUSIONS: The use of bevacizumab during and up to 10 months after carboplatin and paclitaxel chemotherapy prolongs the median progression-free survival by about 4 months in patients with advanced epithelial ovarian cancer. (Funded by the National Cancer Institute and Genentech; ClinicalTrials.gov number, NCT00262847.).


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasms, Glandular and Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Angiogenesis Inhibitors/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab , Carboplatin/administration & dosage , Carcinoma, Ovarian Epithelial , Combined Modality Therapy , Disease-Free Survival , Double-Blind Method , Female , Humans , Middle Aged , Neoplasms, Glandular and Epithelial/mortality , Neoplasms, Glandular and Epithelial/surgery , Ovarian Neoplasms/mortality , Ovarian Neoplasms/surgery , Paclitaxel/administration & dosage , Quality of Life , Survival Analysis , Young Adult
16.
Cancer ; 117(16): 3731-40, 2011 Aug 15.
Article in English | MEDLINE | ID: mdl-21815133

ABSTRACT

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: A weekly topotecan and biweekly bevacizumab combination demonstrates acceptable toxicity and encouraging efficacy in patients with platinum-resistant OC; further study is warranted.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fallopian Tube Neoplasms/drug therapy , Ovarian Neoplasms/drug therapy , Peritoneal Neoplasms/drug therapy , Topotecan/administration & dosage , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab , Drug Administration Schedule , Drug Resistance, Neoplasm , Female , Humans , Middle Aged , Platinum Compounds/pharmacology
17.
J Clin Oncol ; 29(16): 2259-65, 2011 Jun 01.
Article in English | MEDLINE | ID: mdl-21537039

ABSTRACT

PURPOSE: Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor-A (VEGF-A), has clinical activity in multiple tumor types. We conducted a phase II trial to assess the activity and tolerability of single-agent bevacizumab in recurrent or persistent endometrial cancer (EMC). PATIENTS AND METHODS: Eligible patients had persistent or recurrent EMC after receiving one to two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group performance status of ≤ 2. Treatment consisted of bevacizumab 15 mg/kg intravenously every 3 weeks until disease progression or prohibitive toxicity. VEGF-A was assessed by immunohistochemistry in archival tumor and by enzyme-linked immunosorbent assay in pretreatment plasma. Primary end points were progression-free survival (PFS) at 6 months and overall response rate. RESULTS: Fifty-six patients were enrolled. Fifty-two patients were eligible and evaluable. Median age was 62 years, and prior treatment consisted of one or two regimens in 33 (63.5%) and 19 (36.5%) patients, respectively. Twenty-nine patients (55.8%) received prior radiation. Adverse events were consistent with those expected with bevacizumab treatment. No GI perforations or fistulae were seen. Seven patients (13.5%) experienced clinical responses (one complete response and six partial responses; median response duration, 6.0 months), and 21 patients (40.4%) survived progression free for at least 6 months. Median PFS and overall survival times were 4.2 and 10.5 months, respectively. Suggested associations were observed between high VEGF-A and adjusted hazard of death or tumor response when evaluated in tumor/plasma or plasma, respectively. CONCLUSION: Bevacizumab is well tolerated and active based on PFS at 6 months in recurrent or persistent EMC and warrants further investigation.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal/therapeutic use , Endometrial Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized , Bevacizumab , Disease-Free Survival , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/mortality , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Salvage Therapy/methods , Vascular Endothelial Growth Factor A/biosynthesis , Vascular Endothelial Growth Factor A/blood
18.
Gynecol Oncol ; 121(2): 264-8, 2011 May 01.
Article in English | MEDLINE | ID: mdl-21277623

ABSTRACT

OBJECTIVE: This study aimed to determine the first-cycle maximum tolerated dose (MTD) of intraperitoneal carboplatin in combination with intravenous paclitaxel and then assess the feasibility of this dose over multiple cycles. METHODS: Beginning at an intraperitoneal (IP) carboplatin dose area under the curve (AUC) of 5 and a fixed intravenous dose of 175mg/m(2) paclitaxel, patients were entered on a dose-escalating phase evaluating first-cycle dose-limiting toxicity (DLT). After estimating the MTD, cohorts of 20 patients were then entered in an expanded phase to evaluate DLT over four cycles. RESULTS: Twenty-one patients were entered on the dose-escalating phase. A first-cycle MTD of carboplatin at AUC 8 was tolerated although thrombocytopenia was dose-limiting over multiple cycles. An additional 69 patients were treated in expanded cohorts. Only 5/90 (5.6%) patients discontinued treatment because of a port problem. Four-cycle DLT required de-escalation to a carboplatin AUC of 6, and even at that dose, there were 14 dose-limiting toxic effects in 40 patients (35%). Seven dose-limiting toxicities were due to neutropenia, and 6 were due to grade 3/4 thrombocytopenia. Six cycles of therapy were completed in 75% of eligible patients, but dose adjustments were required. CONCLUSIONS: The first-cycle MTD did not predict the tolerability of this regimen over multiple cycles. Using an IP carboplatin dose of AUC 6 in combination with paclitaxel, the regimen can be administered with a high completion rate over multiple cycles. Because neutropenia is a frequent DLT, the addition of hematopoietic growth factors may permit a high completion rate while maintaining this dose.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Fallopian Tube Neoplasms/drug therapy , Ovarian Neoplasms/drug therapy , Peritoneal Neoplasms/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Carboplatin/administration & dosage , Carboplatin/adverse effects , Cohort Studies , Dose-Response Relationship, Drug , Female , Humans , Infusions, Intravenous , Middle Aged , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Young Adult
19.
Cancer ; 117(3): 554-62, 2011 Feb 01.
Article in English | MEDLINE | ID: mdl-20862744

ABSTRACT

BACKGROUND: Primary mucinous adenocarcinomas of the ovary are uncommon, and their biological behavior is uncertain. Retrospective studies have suggested that many mucinous carcinomas initially diagnosed as primary to the ovary have in fact metastasized from another site. A prospective randomized trial provided an opportunity to estimate the frequency of mucinous tumors, diagnostic reproducibility, and clinical outcomes. METHODS: A phase 3 trial enrolled 4000 women with stage III or IV ovarian carcinoma, treated by surgical staging and debulking, with randomization to one of five chemotherapeutic arms. Slides and pathology reports classified as primary mucinous carcinoma were reviewed independently by three pathologists. Cases were reclassified as primary or metastatic to the ovary according to two methods. Overall survival (OS) of reclassified groups was compared within the groups and with that of patients with serous carcinomas. RESULTS: Forty-four cases were classified as mucinous adenocarcinoma upon review. Using either method, only about one third were interpreted by the three reviewers as primary mucinous carcinomas. Reproducibility of interpretations among the reviewers was high, with unanimity of opinion in 30 (68%) cases. The median survival (MS) did not differ significantly between the groups interpreted as primary or metastatic, but the OS was significantly less than that for women with serous carcinoma (14 vs 42 months, P < 0.001). CONCLUSION: Advanced stage mucinous carcinoma of the ovary is very rare and is associated with poor OS. Many mucinous adenocarcinomas that are diagnosed as primary ovarian neoplasms appear to be metastatic to the ovary.


Subject(s)
Adenocarcinoma, Mucinous/mortality , Ovarian Neoplasms/mortality , Adenocarcinoma, Mucinous/drug therapy , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/secondary , Algorithms , Cystadenocarcinoma, Serous/mortality , Disease-Free Survival , Female , Humans , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Ovarian Neoplasms/secondary
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