RESUMO
BACKGROUND: The purpose of this study was to determine the effect of retroperitoneal (RP) exploration on progression-free survival (PFS) and overall survival (OS) in epithelial ovarian cancer (EOC) patients with stage IIIC disease who underwent optimal debulking surgery. METHODS: Data were collected from records of the Gynecologic Oncology Group 182 (GOG-182) study of stage IIIC EOC patients cytoreduced to no gross residual disease (R0) or minimal gross residual (<1 cm) disease (MGRD) at primary surgery. Patients with stage IIIC disease by intraperitoneal (IP) tumor were included and divided into 3 groups: 1) > 2 cm IP tumor without lymph node involvement (IP/RP-), 2) > 2 cm IP tumor with lymph node involvement (IP/RP+), and 3) > 2 cm IP tumor with no RP exploration (IP/RP?). The effects of disease distribution and RP exploration on PFS and OS were assessed using Kaplan-Meier and proportional hazards methods. RESULTS: There were 1871 stage IIIC patients in GOG-182 who underwent optimal primary debulking surgery. Of these, 689 (36.8%) underwent RP exploration with removal of lymph nodes from at least 1 para-aortic site, and 1182 (63.2%) did not. There were 269 patients in the IP/RP- group, 420 patients in the IP/RP + group, and 1182 patients in the IP/RP? group. Improved PFS (18.5 vs 16.0 months; P < .0001) and OS (53.3 vs 42.8 months; P < .0001) were associated with RP exploration versus no exploration. Patients with MGRD had improved PFS (16.8 vs 15.1 months, P = 0.0108) and OS (44.9 vs 40.5 months, P = 0.0076) versus no exploration. CONCLUSIONS: RP exploration at the time of primary surgery in patients with optimally debulked stage IIIC EOC is associated with a survival benefit. Cancer 2017;123:985-93. © 2016 American Cancer Society.
Assuntos
Procedimentos Cirúrgicos de Citorredução , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário , Feminino , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/mortalidade , Razão de Chances , Neoplasias Ovarianas/mortalidade , Espaço Retroperitoneal/cirurgia , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer therapy with few efficacious treatments. METHODS: We enrolled 70 patients with CIPN in a randomized, double-blinded, sham-controlled, cross-over trial to determine if photobiomodulation (PBM)±physiotherapy reduced the symptoms of neuropathy compared to sham treatment. At the conclusion of follow-up, sham-arm patients could cross-over into a third arm combining PBM and physiotherapy to determine if multimodal treatment had additive effects. Treatment included 30minute sessions 3-times weekly for 6weeks using either PBM or sham therapy. Neuropathy was assessed using the modified total neuropathy score (mTNS) at initiation and 4, 8, and 16weeks after initiating treatment. RESULTS: Sham-treated patients experienced no significant change in mTNS scores at any point during the primary analysis. PBM patients experienced significant reduction in mTNS scores at all time points. Mean changes in mTNS score (and corresponding percent drop from baseline) for sham and PBM-group patients respectively were -0.1 (-0.7%) and -4.2 (-32.4%) at 4weeks (p<0.001), 0.2 (0.0%) and -6.8 (-52.6%) at 8weeks (p<0.001), and 0.0 (0.1%) and -5.0 (-38.8%) at 16weeks (p<0.001). Patients who crossed over into the PBM/PT-group experienced similar results to those treated primarily; changes in mTNS score from baseline were -5.5 (-40.6%) 4weeks (p<0.001), -6.9 (-50.9%) at 8weeks (p<0.001), and -4.9 (-35.9%) at 16weeks (p<0.001). The addition of physiotherapy did not improve outcomes over PBM alone. CONCLUSION AND RELEVANCE: Among patients with CIPN, PBM produced significant reduction in neuropathy symptoms.
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Antineoplásicos/efeitos adversos , Terapia com Luz de Baixa Intensidade , Neoplasias/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/terapia , Modalidades de Fisioterapia , Idoso , Idoso de 80 Anos ou mais , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVE: We aimed to evaluate the feasibility and tolerability of hyperthermic intraperitoneal carboplatin (HIPEC-carboplatin) following secondary cytoreduction for recurrent, platinum-sensitive ovarian cancer. METHODS: In a single institution prospective, pilot study, ten patients underwent secondary cytoreductive surgery followed by HIPEC-carboplatin at 1000 mg/m(2). Consolidation (6 cycles) was with platinum-based regimens. Adverse and quality of life were measured throughout treatment. RESULTS: Twelve patients were enrolled of which 2 were excluded (one each for extra-abdominal disease indentified before surgery and suboptimal cytoreduction). All 10 remaining patients received prescribed HIPEC-carboplatin. There were no intra-operative complications or AEs attributable to HIPEC-therapy. Grade 1/2 nausea was the most common post-operative toxicity (6/10 patients). Two patients had grade 4 post-operative neutropenia and thrombocytopenia but only one experienced transient treatment delay. The median hospital stay was 5.5 days. 69/70 (98%) of planned chemotherapy doses were ultimately delivered with 1 patient electively forgoing her final treatment. At a median (range) follow-up of 16 (6-23) months, three patients have recurred at 8, 14, and 16 months from surgery. The median disease-free and overall survivals have not been reached. Fact-O scores were significantly lower following surgery (126 vs. 108, p<.01), but improved by completion of therapy (108 vs. 113, p=0.27). CONCLUSIONS: HIPEC-carboplatin at 1000 mg/m(2) following optimal cytoreduction for ovarian cancer is feasible. Surgical complications were not observed, and post-operative AEs were largely within expected ranges. Consolidation using standard platinum-based regimens was feasible following HIPEC-carboplatin, and preliminary survival data suggests efficacy. Further investigation of HIPEC-carboplatin in the setting of debulkable cancer recurrence is warranted.
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Antineoplásicos/administração & dosagem , Carboplatina/administração & dosagem , Hipertermia Induzida , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/terapia , Idoso , Antineoplásicos/efeitos adversos , Carboplatina/efeitos adversos , Terapia Combinada , Feminino , Humanos , Injeções Intraperitoneais , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Projetos Piloto , Estudos ProspectivosRESUMO
BACKGROUND: Natural killer (NK) cells derived from patients with cancer exhibit diminished cytotoxicity compared with NK cells from healthy individuals. We evaluated the tumor response and in vivo expansion of allogeneic NK cells in recurrent ovarian and breast cancer. METHODS: Patients underwent a lymphodepleting preparative regimen: fludarabine 25 mg/m(2) × 5 doses, cyclophosphamide 60 mg/kg × 2 doses, and, in seven patients, 200 cGy total body irradiation (TBI) to increase host immune suppression. An NK cell product, from a haplo-identical related donor, was incubated overnight in 1000 U/mL interleukin (IL)-2 prior to infusion. Subcutaneous IL-2 (10 MU) was given three times/week × 6 doses after NK cell infusion to promote expansion, defined as detection of ≥100 donor-derived NK cells/µL blood 14 days after infusion, based on molecular chimerism and flow cytometry. RESULTS: Twenty (14 ovarian, 6 breast) patients were enrolled. The median age was 52 (range 30-65) years. Mean NK cell dose was 2.16 × 10(7)cells/kg. Donor DNA was detected 7 days after NK cell infusion in 9/13 (69%) patients without TBI and 6/7 (85%) with TBI. T-regulatory cells (Treg) were elevated at day +14 compared with pre-chemotherapy (P = 0.03). Serum IL-15 levels increased after the preparative regimen (P = <0.001). Patients receiving TBI had delayed hematologic recovery (P = 0.014). One patient who was not evaluable had successful in vivo NK cell expansion. CONCLUSIONS: Adoptive transfer of haplo-identical NK cells after lymphodepleting chemotherapy is associated with transient donor chimerism and may be limited by reconstituting recipient Treg cells. Strategies to augment in vivo NK cell persistence and expansion are needed.
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Neoplasias da Mama/imunologia , Neoplasias da Mama/terapia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/transplante , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Infusões Intravenosas , Interleucina-15/sangue , Células Matadoras Naturais/citologia , Células Matadoras Naturais/efeitos dos fármacos , Depleção Linfocítica , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/tratamento farmacológico , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Transplante Homólogo , Irradiação Corporal Total/efeitos adversosRESUMO
OBJECTIVE: To determine the disease characteristics and comorbidities predictive of vulvar cancer specific mortality and five year overall survival among older women, ages 65 and above. METHODS: A retrospective analysis was conducted of women diagnosed with vulvar cancer at a single regional cancer center from 1989 to 2003, with a follow up to 2009. Treatment records were extracted for: demographics and treatment information, Eastern Cooperative Oncology Group (ECOG) performance status and Charlson comorbidity index score. Probability of death from vulvar cancer was estimated using cumulative incidence, treating death by other known and unknown causes as competing risks. Predictors of overall survival were determined using multivariate Cox regression analyses. RESULTS: One hundred forty-six women were identified, with a median age at diagnosis of 79 years (range 65-95). Median follow up was 5.0 years (range 0.1-16.7 years). The cumulative incidence of vulvar cancer-specific mortality was 13% (95% CI: 0.08-0.19) at year one, 24% (95% CI: 0.17-0.31) at year three and 26% (95% CI: 0.19-0.33) at year five. Use of adjuvant therapy or surgical procedure performed did not differ by age at diagnosis (p=0.807 and 0.663) according to age group (65-74, 74-84 and 85+). Increasing age, Charlson comorbidity index score, lymph node involvement and type of surgery performed were associated with increased risk of death from any cause (all p<0.05). CONCLUSION: Among women aged ≥65, vulvar cancer specific mortality was most significant in the first three years after diagnosis. Conversely other causes of mortality which can be attributed to comorbid conditions steadily increased with time.
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Neoplasias Vulvares/mortalidade , Neoplasias Vulvares/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Causas de Morte , Comorbidade , Feminino , Humanos , Minnesota/epidemiologia , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
OBJECTIVES: (1) To determine the response rate of advanced, recurrent, or persistent carcinoma of the cervix to ifosfamide, paclitaxel, and carboplatin chemotherapy; (2) to determine the progression free interval and survival rate in patients treated with this regimen; (3) to describe the toxicities associated with this regimen; and (4) to evaluate the quality of life of patients while on treatment. METHODS: Eligible patients had histologically proven stage IVB, recurrent, or persistent carcinoma of the cervix not amenable to curative treatment with surgery and/or radiation therapy. Chemotherapy was given on day 1 of a 28-day cycle: mesna (600 mg/m(2)) prior to ifosfamide (2 g/m(2)), paclitaxel (175 mg/m(2)), carboplatin (AUC 5). Response rates were determined according to RECIST criteria. Toxicity was graded according the National Cancer Institute's common toxicity criteria. Quality of life measurements were obtained using the FACT-Cx. RESULTS: Twenty-eight patients participated in this study, with 21 evaluable for response rate. Overall, 7 patients (33%) had a demonstrated objective response (4 complete responses, 3 partial responses). Stable disease was documented in 3 patients. The overall median survival for all patients was 10 months. Median progression free survival for evaluable patients was 5.0 months. Bone marrow suppression was the most common toxicity. There were no negative effects of this treatment regimen on quality of life assessments. CONCLUSION: Ifosfamide, paclitaxel, and carboplatin is an effective regimen in treating advanced or recurrent carcinoma of the cervix and has an acceptable toxicity profile.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Feminino , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Qualidade de Vida , Neoplasias do Colo do Útero/patologia , Adulto JovemRESUMO
OBJECTIVES: Despite increased use of integrative medicine in cancer therapy, little data exist on its efficacy. This prospective, randomized, pilot trial sought to evaluate the feasibility of combined modality integrative medicine (CM-IM) in women with ovarian cancer (OvCA) and evaluate its effects on quality of life (QoL), chemotherapy toxicity and immunologic profiles. METHODS: Women with newly diagnosed OvCA requiring chemotherapy were offered enrollment. Those randomized to the experimental arm received hypnosis, therapeutic massage and healing touch with each cycle of chemotherapy. The control arm received chemotherapy without CM-IM. All patients completed QoL questionnaires prior to cycles 1, 3 and 6, and 6-months after chemotherapy. Immunologic profiles were measured. Statistical analysis was based on intent-to-treat. Student's t-test and Fischer's exact-test were used to determine differences. RESULTS: Forty-three women enrolled. All women randomized to CM-IM were successfully treated. There were no statistical differences between the groups in age, stage, grade, histologic cell type, CA125 levels, or surgical cytoreductive status. There was no difference in overall QoL measurements. Re-hospitalization rates, treatment delays, anti-emetic use, and infection rates were similar. Immunologic profiles revealed no difference between arms for WBC or salivary IgA levels. Women receiving CM-IM had consistently higher levels of CD4, CD8 and NK cells, although this did not reach statistical significance. CONCLUSIONS: Prospective clinical evaluation of integrative medicine for women with gynecologic malignancy is feasible. This first, pilot study of CM-IM in gynecologic oncology demonstrated no improvement in QoL or chemotherapy toxicity. Integrative medicine-associated improvements in immunologic profiles warrant further investigation.
Assuntos
Medicina Integrativa , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/psicologia , Projetos Piloto , Estudos Prospectivos , Qualidade de VidaRESUMO
OBJECTIVE: To determine feasibility and efficacy of administering docetaxel and carboplatin chemotherapy followed by pelvic radiotherapy and then consolidation chemotherapy in patients with advanced or recurrent endometrial cancer. METHODS: Patients with surgically staged III-IV (excluding IIIA from positive cytology alone) endometrial cancer or biopsy confirmed recurrent disease were eligible. Treatment consisted of 3 cycles of docetaxel (75 mg/m²) and carboplatin (AUC 6) on a q21 day schedule followed by involved field irradiation (45 Gy)± brachytherapy and three additional cycles of docetaxel and carboplatin. Kaplan-Meier (KM) methods estimated overall survival (OS) and progression free survival (PFS). RESULTS: Forty-two patients enrolled, 7 did not complete therapy. 95% (39/41) had primary disease. Median age=58 years (range: 21-81 years). 78% (32/41)=endometrioid histology. Stages=10 IIIA, 21 IIIC, 1 IVA, 7 IVB, (recurrent=1 IC, 1 IIA). There were 23 non-hematologic and 14 grade 3 and 16 grade 4 hematologic toxicities. Seven patients died following treatment with a median follow-up of 28 months (range: 7-70 months). KM estimates and 95% confidence intervals for OS at 1 year were 95% (82-99%), at 3 years 90% (75-96%), and at 5 years 71% (45-86%). Of the 39 with primary disease, 11 progressed or died within 5 years of study enrollment. KM estimates and 95% confidence intervals for PFS at 1 year were 87% (72-94%), at 3 years 71% (51-83%), and at 5 years 64% (42-80%). CONCLUSIONS: "Sandwiching" radiation between chemotherapy for advanced or recurrent endometrial cancer merits further development based on the reported PFS and OS.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma Endometrioide/radioterapia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/radioterapia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Braquiterapia/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Endometrioide/patologia , Terapia Combinada/efeitos adversos , Intervalo Livre de Doença , Docetaxel , Fracionamento da Dose de Radiação , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: The primary objective was to study the antitumor activity of prolonged subcutaneous dosing of systemic 852A, a Toll-like receptor-7 agonist (TLR-7), in recurrent breast, ovarian and cervix cancer. Secondary objectives included assessment of safety and immune system activation. METHODS: Adults with recurrent breast, ovarian or cervix cancer failing multiple therapies received 0.6 mg/m(2) of 852A subcutaneously twice weekly for 12 weeks. Doses increased by 0.2 mg/m(2)/week to a maximum of 1.2 mg/m(2). Serum was collected to assess immune activation. RESULTS: Fifteen patients enrolled: 10 ovarian, 2 cervix and 3 breast. Three completed all 24 injections. There were two grade 2 (decreased ejection fractions), nine grade 3 (1 cardiovascular, 1 anorexia, 3 dehydration, 2 infections, 2 renal) and two grade 4 (hepatic and troponin elevation) unanticipated toxicities. Cardiac toxicities included three cardiomyopathies (2 asymptomatic) and one stress-related non-ST elevated myocardial infarction. Five patients discontinued therapy due to possibly associated side effects. One who had stable disease (SD) following 24 doses received 17 additional doses. A cervix patient with SD following 24 doses received chemotherapy after progressing 3 months later, and remains disease free at 18 months. Immune activation, as evidenced by increased IP-10 and IL-1ra, was observed. CONCLUSIONS: In this first human experience of a TLR-7 agonist delivered subcutaneously using a prolonged dosing schedule, 852A demonstrated sustained tolerability in some patients. Clinical benefit was modest, but immune activation was seen suggesting further study of antitumor applications is warranted. Because of cardiac toxicity; 852A should be used cautiously in heavily pretreated patients.
Assuntos
Aminoquinolinas/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Sulfonamidas/administração & dosagem , Receptor 7 Toll-Like/agonistas , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Idoso , Aminoquinolinas/efeitos adversos , Aminoquinolinas/imunologia , Antineoplásicos/efeitos adversos , Antineoplásicos/imunologia , Esquema de Medicação , Feminino , Humanos , Injeções Subcutâneas , Pessoa de Meia-Idade , Estudos Prospectivos , Quinolinas , Sulfonamidas/efeitos adversos , Sulfonamidas/imunologiaRESUMO
OBJECTIVE: Effective patient -clinician communication at diagnosis is important, yet decreased provider time for face-to-face interactions makes traditional paradigms in cancer care difficult. We evaluated the effects of an educational video on patients' distress, cancer knowledge, coping skills and attitudes regarding learning about cancer at the time of ovarian cancer diagnosis. METHODS: An educational video was developed in which oncology professionals, women with ovarian cancer, and their relatives discussed cancer information and experiences. Women admitted for initial diagnostic surgical staging for ovarian cancer were randomized to the educational or placebo video. Before and after the video, patients completed measures of (1) ovarian cancer information, (2) emotional distress, (3) learning attitudes, and (4) coping self-efficacy. Outcomes were analyzed for differences in mean change between intervention and placebo groups using t-tests. RESULTS: Fifty-nine subjects were randomized (30 intervention/29 placebo). The majority were advanced staged, white, insured, high school educated, employed, and rated their disease seriousness as high. Anxiety, general distress and cancer-specific distress were high. Pre-post video: distress and self-efficacy between groups were unchanged, intervention subjects answered more knowledge items correctly (p=0.0004) and developed more negative learning attitudes (p=0.037). Following the educational video, patients who developed more negative attitudes also had increased intrusive thinking (p=0.046), a sign of increased distress. CONCLUSIONS: Video presentation of cancer-related information increases learning under conditions of high distress and disease threat however, it is not without risk for some. Differing information needs may affect women's emotional response under these conditions.
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Neoplasias Ovarianas/psicologia , Educação de Pacientes como Assunto/métodos , Adaptação Psicológica , Atitude , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Aprendizagem , Pessoa de Meia-Idade , Gravação em VídeoRESUMO
Objective. The goal of treating recurrent ovarian cancer is disease control while minimizing toxicity. Fulvestrant, a novel estrogen receptor (ER) antagonist, has proven clinically beneficial and well-tolerated in treating recurrent breast cancer. Ovarian cancer often expresses ER and may respond to anti-estrogen therapy. We evaluated fulvestrant in women with recurrent ovarian or primary peritoneal cancer. Methods. Patients with ER-positive, multiply recurrent ovarian or primary peritoneal carcinoma and either measurable disease according to RECIST criteria or an abnormal and rising CA-125 were eligible for enrollment. Treatment consisted of single agent fulvestrant, 500 mg IM on Day 1, 250 mg IM on Day 15, and 250 mg IM on Day 29 and every 28 days thereafter until either intolerance or disease progression. Disease response was assessed by monthly physical exams and CA-125 levels as well as CT scans bimonthly. The primary endpoint was clinical benefit (CB=complete response (CR)+partial response (PR)+stable disease (SD)) at 90 days. Results. Thirty-one women were enrolled and 26 women (median age of 61) met inclusion criteria and received at least one dose. Patients had received a median of 5 prior chemotherapeutic regimens (range: 2-13). We observed one CR (4%), one PR (4%), and 9 patients with SD (35%) using modified-Rustin criteria (CA-125 level). Using modified-RECIST criteria 13 patients (50%) achieved SD. The median time to disease progression was 62 days (mean 86 days). Grade 1 toxicity included headache (1 patient) and bromidrosis (2 patients). Conclusions. Fulvestrant is well-tolerated and efficacious. Objective response rates are low, but disease stabilization was common.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Estradiol/análogos & derivados , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Fosfatase Alcalina/sangue , Antineoplásicos Hormonais/efeitos adversos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Colágeno Tipo I/urina , Estradiol/efeitos adversos , Estradiol/uso terapêutico , Feminino , Fulvestranto , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Neoplasias Ovarianas/metabolismo , Peptídeos/urinaRESUMO
OBJECTIVE: To determine if pelvic examination affected management in patients undergoing first-line chemotherapy for ovarian cancer and to determine a threshold of change in tumor size reliably detectable by pelvic examination. STUDY DESIGN: We reviewed 501 encounters among 47 women with ovarian cancer to see if pelvic examination prompted a management change. Clinicians then evaluated synthetic model "tumors" and were retested at intervals of 3-48 hours to determine change needed for reliable detection. RESULTS: The median number of examinations was 3 during 8 cycles of chemotherapy. Fifteen examinations (10.5%) revealed palpable anomalies, attributable to known tumor in 10 instances. The most common events preceding management change were elevation in serum CA-125 (57%) or chemotherapy toxicity (20%). No changes were made based on pelvic examination alone. When assessing "tumor" volume in a model, estimates ranged from 33-309% of actual volume. Determination of volume change following a delay was poor. No reliable threshold of detection of volume change was established. CONCLUSION: Pelvic examination findings rarely dictated management changes in this study. Further, our results call into question the potential of routine pelvic examination to add significantly to clinical management during initial treatment given the wide range of error in "tumor" size estimates.
Assuntos
Antineoplásicos/efeitos adversos , Antígeno Ca-125/sangue , Neoplasias Ovarianas/patologia , Pelve/patologia , Exame Físico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Neoplasias Ovarianas/tratamento farmacológicoRESUMO
OBJECTIVE: To investigate the efficacy and safety of bevacizumab in heavily pretreated patients with recurrent ovarian cancer. METHODS: Patients with recurrent ovarian cancer were treated with intravenous bevacizumab 10 mg/kg every other week plus oral cyclophosphamide 50 mg daily until disease progression or undue toxicity. Adverse events were graded according to the NCI Common Toxicity Criteria. Response rates were determined by CA-125 levels or changes in target lesions according to RECIST. RESULTS: Fifteen patients were treated. Median age was 57 years (range 42-69). The median number of previous chemotherapy regimens was 8 (range 5-15). The median time from the first diagnosis to treatment with bevacizumab was 68.9 months (range, 26.5-177.2). The median number of bevacizumab infusions was 8 (range, 2-12), and the total number was 113. Two patients (13.3%) had a complete response after 4 months of therapy. Six patients (40.0%) had a partial response. The median duration of this response was 3.9 months (range, 2.3-10.4). Three patients (20%) had stable disease of 4.0, 5.2 and 5.5 months' duration, and 4 patients (26.7%) had progressive disease. Despite being heavily pre-treated and having confirmed intra-abdominal cancer, no gastrointestinal perforations developed. Other toxicities included: grade 3 pancreatitis in 1 patient; grade 2 proteinuria and hypertension in another, which resolved with the cessation of bevacizumab. CONCLUSION: In our population of very heavily pre-treated patients, with at least five prior regimens, bevacizumab in combination with oral cyclophosphamide has significant activity with a response rate of 53%, without significant toxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Administração Oral , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva , Projetos de Pesquisa , Estudos Retrospectivos , Terapia de Salvação/métodos , Resultado do TratamentoRESUMO
OBJECTIVE: To estimate whether a rapid recovery program would reduce length of stay among patients undergoing laparotomy on a gynecologic oncology service. METHODS: We conducted a prospective, randomized, controlled trial comparing an enhanced recovery after surgery protocol with routine postoperative care among women undergoing laparotomy on the gynecologic oncology service. Protocol elements included: preoperative counseling, regional anesthesia, intraoperative fluid restriction, and early postoperative ambulation and feeding. A sample size of 50 per group (N=100) was planned to achieve 80% power to detect a two-day difference in our primary outcome, length of hospital stay; secondary outcomes included: total daily narcotics used, time to postoperative milestones, and complications. RESULTS: A total of 112 women were enrolled between 2013 and 2015. Nine patients did not undergo laparotomy and were excluded, leaving 52 and 51 patients in the control and intervention groups, respectively. There was no difference in length of stay between the two groups (median 3.0 in both groups; P=.36). Enhanced recovery after surgery patients used less narcotics on day 0 (10.0 compared with 5.5 morphine equivalents in the control and intervention arms, respectively, P=.09) and day 2 (10.0 compared with 7.5 morphine equivalents, respectively; P=.05); however, there was no statistically significant difference between groups in any of the secondary outcomes. Post hoc analysis based on actual anesthesia received also failed to demonstrate a difference in time to discharge. CONCLUSION: When compared with usual care, introducing a formal enhanced recovery after surgery protocol did not significantly reduce length of stay. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01705288.
Assuntos
Neoplasias dos Genitais Femininos/cirurgia , Procedimentos Cirúrgicos em Ginecologia/reabilitação , Laparotomia/reabilitação , Tempo de Internação , Cuidados Pós-Operatórios/métodos , Anestesia/métodos , Anestesia/estatística & dados numéricos , Deambulação Precoce/estatística & dados numéricos , Feminino , Humanos , Pessoa de Meia-Idade , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/epidemiologia , Período Pós-Operatório , Cuidados Pré-Operatórios/métodos , Cuidados Pré-Operatórios/estatística & dados numéricos , Estudos Prospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To estimate the effect of preoperative diagnostic hysteroscopy on peritoneal cytology in patients with endometrial cancer. METHODS: A total of 256 charts were reviewed. Two cohorts were established based on diagnosis by hysteroscopy or blind endometrial sampling via either endometrial biopsy or dilatation and curettage (D&C). Malignant or suspicious peritoneal cytology was the primary outcome. Cohorts were compared using logistic regression to correct for potential confounders of stage and grade. RESULTS: A total of 204 cases were diagnosed by endometrial biopsy or D&C, whereas 52 were identified by hysteroscopy. In the endometrial biopsy or D&C arm, 14 of 204 (6.9%) patients had malignant or suspicious cytology compared with 7 of 52 (13.5%) patients in the hysteroscopy arm (P = .15). After logistic regression controlling for stage and grade, the odds ratio for positive cytology after hysteroscopy was 3.88 (95% confidence interval 1.11,13.6; P = .03). Four of the 52 (7.7%) cases diagnosed by hysteroscopy were stage IIIA due to cytology alone compared with 3 of the 204 (1.4%) cases diagnosed by endometrial biopsy or D&C (P = .03). CONCLUSION: Hysteroscopy appears to be associated with an increased rate of malignant cytology after controlling for confounders of stage and grade. Further, there appears to be an association between hysteroscopy and upstaging patients due to cytology alone. LEVEL OF EVIDENCE: II-2.
Assuntos
Neoplasias do Endométrio/diagnóstico , Histeroscopia , Biópsia , Dilatação e Curetagem , Neoplasias do Endométrio/patologia , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , PrognósticoRESUMO
BACKGROUND: Thalidomide is an antiangiogenic agent with immune modulating potential. The objective of this study was to determine response rates among women who were treated for recurrent ovarian cancer using topotecan with or without thalidomide. METHODS: Women were enrolled in this multicenter, prospective, randomized phase 2 trial between April 2001 and July 2005. Eligible patients had recurrent epithelial ovarian carcinoma with measurable disease or elevated CA 125 values. Patients had received prior platinum-based chemotherapy. Treatment arms received topotecan at a dose of 1.25 mg/m(2) on Days 1 through 5 of a 21-day cycle with or without thalidomide starting at a dose of 200 mg per day and then increasing the dose as tolerated. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria. The chi-square test was used to assess differences in response and toxicity, and the log-rank test was used to compare Kaplan-Meier survival curves. RESULTS: The analysis included 69 women (39 women in the control arm and 30 women in the thalidomide arm). Known prognostic factors, including platinum sensitivity, were represented equally in each arm. The median thalidomide dose was 200 mg per day. The overall response rate in the control arm was 21% (complete response [CR] rate, 18%; partial response [PR] rate, 3%) compared with 47% in the thalidomide arm (CR rate, 30%; PR rate, 17%) (P= .03). The median progression-free survival for the control arm was 4 months compared with 6 months in the thalidomide arm (P= .02). The median overall survival was 15 months in the control arm and 19 months in the thalidomide arm (P= .67). Toxicities were similar between groups. CONCLUSIONS: The addition of thalidomide to topotecan for the treatment of recurrent ovarian cancer appears to improve response rates, and the authors believe that it warrants study through larger phase 3 trials.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Talidomida/administração & dosagem , Topotecan/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Talidomida/efeitos adversos , Topotecan/administração & dosagem , Topotecan/efeitos adversosRESUMO
OBJECTIVES: To determine progression-free survival (PFS) and overall survival (OS) in women with completely resected stage I or II carcinosarcoma of the uterus treated with adjuvant ifosfamide and cisplatin, and to assess the toxicity of this regimen. METHODS: Eligible patients had histologically confirmed carcinosarcoma (mixed mesodermal tumor) and no postoperative radiotherapy following complete resection for clinical stage I or II disease. They were to have adequate renal, hepatic, and hematologic functions and performance status of 2 or less. Study entry was to be within 8 weeks of hysterectomy. Patients with previous chemotherapy, or other noncutaneous malignancies, were ineligible. Ifosfamide was administered 1.5 g/m2 intravenously (IV) over 1 h and cisplatin was given 20 mg/m(2) over 15 min followed by mesna 120 mg/m2 IV bolus, then 1.5 g/m2/24 h as a continuous infusion. Initial doses (daily x 5 every 21 days x 3 cycles) were reduced by 20% (to 4 days) for myelotoxicity. RESULTS: Nine of seventy-six patients enrolled were deemed ineligible and another two who did not receive protocol treatment were inevaluable. Of the 65 evaluable patients, median age was 65 years; 50 patients (77%) were stage I and 15 (23%) were stage II. PFS and OS, respectively, were 69% and 82% at 24 months, and 54% and 52% at 84 months. Overall 5-year survival was 62%. Leukopenia was the most commonly reported, but manageable, toxicity. CONCLUSION: Adjuvant ifosfamide and cisplatin after primary surgery for stage I or II carcinosarcoma of the uterus is tolerable. In the absence of concurrent controls, the impact on PFS and OS is unclear. Pelvic relapse remains problematic.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinossarcoma/tratamento farmacológico , Tumor Mesodérmico Misto/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinossarcoma/patologia , Carcinossarcoma/cirurgia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Infusões Intravenosas , Pessoa de Meia-Idade , Tumor Mesodérmico Misto/patologia , Tumor Mesodérmico Misto/cirurgia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgiaRESUMO
BACKGROUND: Lymphatic and hematologic metastases are rare in microinvasive cervical cancers (FIGO stage IA1), supporting a role for conservative treatment. Cervical conization followed by prolonged surveillance is an accepted treatment in patients with low-risk features and negative surgical margins. This option is particularly appealing for younger or nulliparous patients, in whom fertility may be highly desired. CASE: We report a case of a 22-year-old, HIV-negative female with stage IA1 squamous cell cervical carcinoma who was found to have bilateral lymph node metastases in both pelvic and para-aortic distributions after electing to undergo hysterectomy. CONCLUSION: Clinicians treating patients with microinvasive cervical cancer conservatively must be aware of the possibility of lymph node involvement and should consider radiological imaging to look for metastatic disease.
Assuntos
Carcinoma de Células Escamosas/patologia , Linfonodos/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Histerectomia , Metástase Linfática , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/cirurgiaRESUMO
OBJECTIVES: The aim of this study was to determine cervical cancer cell sensitivity to chemotherapy-induced apoptosis based on human papillomavirus (HPV) status. METHODS: CaSki (HPV-positive) and C33A (HPV-negative) cells were treated with camptothecin or cisplatin. Cellular viability was determined by trypan blue exclusion. Apoptotic indexes were determined by flow cytometric analysis of annexin V labeling and morphological changes. Mitochondrial release of cytochrome c was determined by immunofluorescence using confocal microscopy. Caspase 3 activation and bax expression were assessed by immunoblotting. RESULTS: CaSki cells displayed chemoresistance to both camptothecin and cisplatin. Low response to apoptogenic stimuli was evidenced by a marginal increase in the apoptotic cell fraction after camptothecin treatment (22.9 +/- 2.56%) compared with control (17.8 +/- 1.95%). Cisplatin (14.8 +/- 1.01%) caused a slight decrease in apoptosis. Mitochondrial release of cytochrome c and cleavage of caspase 3 could not be demonstrated in CaSki cells after treatment. Despite p53 mutation, C33A cells were sensitive to the antiproliferative effects of camptothecin and cisplatin. Mean apoptotic events were 17.5 +/- 0.33 for control, 42 +/- 1.76 for cisplatin, and 38.1 +/- 0.75 for camptothecin. An intact cytochrome c pathway was demonstrated in C33A cells leading to cleavage of caspase 3 after camptothecin treatment. The constitutive bax expression demonstrated in both cell lines displayed no change after camptothecin treatment. CONCLUSION: HPV-positive cervical cancer cells have an inherent resistance to chemotherapy-induced apoptosis. HPV-dependant inactivation of apoptotic regulators such as p53 and blockage of downstream events such as cytochrome c release and caspase 3 activation might be elemental to this cellular survival advantage provided by high-risk oncogenic papillomavirus.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Camptotecina/farmacologia , Cisplatino/farmacologia , Papillomaviridae , Proteínas Proto-Oncogênicas c-bcl-2 , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/virologia , Anexina A5 , Caspase 3 , Caspases/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Grupo dos Citocromos c/metabolismo , Ativação Enzimática , Feminino , Citometria de Fluxo , Humanos , Proteínas Proto-Oncogênicas/biossíntese , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/patologia , Proteína X Associada a bcl-2RESUMO
OBJECTIVES: To determine toxicity and establish a maximum tolerated dose of outpatient therapy with ifosfamide, paclitaxel, and carboplatin in women with advanced and recurrent cervical cancer. METHODS: Eligible patients had stage IVB, recurrent or persistent cervical cancer that was not amenable to curative treatment with surgery or radiation therapy. A dose escalation through four dose levels was planned. Dose limiting toxicities were defined as grade 3 or grade 4 hematologic toxicity persistent to day 1 of the next scheduled cycle, grade 2 or higher central neurologic symptoms related to ifosfamide and grade 3 or grade 4 peripheral neuropathy. RESULTS: Twelve patients, aged 29 to 71, received 64 treatments and were evaluable for toxicity. No patient was withdrawn from the study due to toxicity. Two patients had received prior radiation therapy without chemotherapy, and seven patients had received radiation therapy with concurrent chemotherapy. No dose limiting toxicity occurred at dose levels 1 or 2. Three dose reductions occurred at dose level 3 due to neutropenia and thrombocytopenia. The maximum tolerated dose is ifosfamide 2 g/m(2) over 2 h, paclitaxel 175 mg/m(2) over 1 h, and carboplatin at an AUC of 5 over 45 min. Grade 3 or grade 4 neutropenia was seen in 11 subjects. Two patients required growth factor support. Grade 3 or grade 4 anemia was seen in one patient. Grade 3 or grade 4 neuropathy was seen in one patient. Other grade 3 or grade 4 non-hematologic toxicity included muscle weakness, myalgia, cough, and shortness of breath. CONCLUSIONS: Combination therapy with ifosfamide 2 g/m(2), paclitaxel 175 mg/m(2), carboplatin AUC = 5 appears to be a safe regimen for the outpatient treatment of women with advanced or recurrent cervical cancer and warrants phase II investigation.