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2.
Arch Gynecol Obstet ; 301(5): 1235-1245, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32206877

RESUMO

PURPOSE: To examine trends, characteristics and outcomes of women who develop both ovarian and breast cancers. METHODS: This is a retrospective study examining the Surveillance, Epidemiology, and End Results Program from 1973 to 2013. Among ovarian cancer (n = 133,149) and breast cancer (n = 1,143,219) cohorts, women with both diagnoses were identified and temporal trends, tumor characteristics and survival were examined. RESULTS: There were 6446 women with both malignancies, representing 4.8% of the ovarian cancer cohort and 0.6% of the breast cancer cohort. Women with ovarian cancer who had secondary breast cancer were younger than those without secondary breast cancer early in the study period (52.3 versus 59.2 in 1973) but older in more recent years (68.5 versus 62.1 in 2013, P < 0.001). The number of breast cancer survivors who developed postcedent ovarian cancer decreased from 1.5 to 0.2% from 1979 to 2008 (relative risk reduction 90.0%, P < 0.05). Similarly, the number of ovarian cancer survivors who developed postcedent breast cancer decreased from 7.2 to 2.0% from 1973 to 2008 (relative risk reduction 72.4%, P < 0.05). Tumor characteristics were more likely to be favorable in women with ovarian cancer who developed postcedent breast cancer but unfavorable in those who had antecedent breast cancer (all, P < 0.05). Women with ovarian cancer who had secondary breast cancer had superior cause-specific survival compared to those who did not develop breast cancer regardless of breast cancer timing (P < 0.05). CONCLUSION: Our study demonstrated that the demographics of women who develop breast cancer and ovarian cancer have changed over time and diagnosis of secondary breast cancer after ovarian cancer has decreased.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/patologia , Adulto , Idoso , Neoplasias da Mama/mortalidade , Sobreviventes de Câncer , Carcinoma Epitelial do Ovário/mortalidade , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Estudos Retrospectivos , Risco , Sobreviventes
3.
Laryngoscope ; 130(11): 2607-2610, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-31800100

RESUMO

OBJECTIVES/HYPOTHESIS: Advances in cancer treatment have increased survival for many patients, prompting a need for greater recognition of the long-term complications of treatment. Chemotherapy agents have the potential to induce carcinogenesis and can increase the risk of secondary malignancy. Pegylated liposomal doxorubicin (PLD) used for maintenance treatment of recurrent high-grade serous cancers has been associated with the development of oral cavity squamous cell carcinoma (SCC). STUDY DESIGN: Retrospective review. METHODS: Cases of oral cavity SCC in patients with recurrent high-grade serous cancer treated with PLD between 1997 and 2017 at a single institution were reviewed. RESULTS: Eight of 16 patients treated with PLD developed oral cavity SCC. The duration of PLD use ranged from 1.3 to 15 years (mean = 5.8 years) and cumulative dose ranged from 405 to 3,000 mg/m2 (mean = 1,542 mg/m2 ). Seven patients tested positive for BRCA mutations (four BRCA 1+, three BRCA 2+). No patients had a history of alcohol or tobacco use. All had early-stage oral cavity disease; five were T1N0, two were T2N0, and one had carcinoma in situ. All patients underwent surgery, and two received adjuvant radiation. Four developed locoregional recurrence requiring additional treatment. Of these, one patient died from complications of oral SCC, one developed recurrent ovarian cancer, and two had no evidence of disease of the oral cavity or ovarian cancer at the last follow-up. CONCLUSIONS: Long-term PLD therapy may be associated with the development of oral cavity SCC. A high index of suspicion and routine head and neck examination should be included in follow-up for exposed patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2607-2610, 2020.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Carcinoma de Células Escamosas/induzido quimicamente , Doxorrubicina/análogos & derivados , Neoplasias Bucais/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Doxorrubicina/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Estudos Retrospectivos
4.
J Clin Med ; 8(5)2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31137471

RESUMO

The current study examined trends, characteristics, and outcomes of women with uterine cancer who had secondary colorectal cancer. This is a retrospective study utilizing the Surveillance, Epidemiology, and End Results Program between 1973-2013. Among uterine cancer (n = 246,272) and colorectal cancer (n = 421,312) cohorts, women with both diagnoses were identified, and clinico-pathological factors and survival were extracted and analyzed. There were 6862 women with both cancer diagnoses, representing 2.8% of the uterine cancer cohort and 1.6% of the colorectal cancer cohort. Among 123,940 women with uterine cancer survivors, the number with postcedent colorectal cancer decreased from 5.3% to 0.7% between 1981-2008 (relative risk reduction 87.0% p < 0.001). Similarly, of 141,801 women with colorectal cancer survivors, the number with postcedent uterine cancer decreased from 1.7% to 0.5% between 1973-2008 (relative risk reduction 71.6%, p < 0.001). In the uterine cancer cohort, women with antecedent/synchronous colorectal cancer had more high-grade tumors and advanced-stage disease resulting in poorer survival, whereas those who had postcedent colorectal cancer had more low-grade tumors and early-stage disease resulting in superior survival compared to those without secondary colorectal cancer (all, p < 0.05). In conclusion, the development of postcedent colorectal cancer following uterine cancer has decreased in recent years in the United States.

5.
Gynecol Oncol ; 154(1): 169-176, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31130286

RESUMO

OBJECTIVE: To report population-based statistics of women with uterine cancer and a history of prior breast cancer. METHODS: This is a retrospective study examining the Surveillance, Epidemiology, and End Results Program between 1973 and 2013. Temporal trends, clinico-pathological characteristics, and survival of women with uterine cancer who had prior breast cancer were assessed. RESULTS: Among 237,686 women with uterine cancer, 8235 (3.5%) women had antecedent breast cancer. The number of women with uterine cancer who had a history of breast cancer increased between 1975 and 1989 (21.1-fold relative risk-increase, P < 0.001) and then decreased between 1989 and 2013 (relative risk-reduction [RRR] 11.1%, P = 0.008). The number of uterine cancer among breast cancer survivors decreased between 1990 and 2008 (RRR, 86.0%, P < 0.001). Women with uterine cancer and antecedent breast cancer were more likely to be older and white compared to those without a history of breast cancer (P < 0.05). Uterine tumors after breast cancer were more likely to have serous (10.5% versus 5.7%), carcinosarcoma (8.9% versus 4.4%), or clear cell (2.1% versus 1.2%) histology and present with grade 3 (30.8% versus 21.5%) and stage I disease (64.6% versus 62.5%) compared to tumors in women without breast cancer (all, P < 0.05). After propensity score matching, women with uterine cancer after breast cancer were less likely to die from uterine cancer (adjusted-hazard ratio [HR] 0.675) but more likely to die from other malignancies (adjusted-HR 4.090), particularly breast cancer, and had poorer overall survival (adjusted-HR 1.154) compared to those without breast cancer. CONCLUSION: The diagnosis of uterine cancer after breast cancer is decreasing. While uterine tumors following breast cancer are associated with high-risk tumor characteristics, women with uterine cancer after breast cancer are more likely to die from other malignancies.


Assuntos
Neoplasias da Mama/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Neoplasias Uterinas/epidemiologia , Fatores Etários , Idoso , Neoplasias da Mama/mortalidade , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Segunda Neoplasia Primária/mortalidade , Sistema de Registros , Estudos Retrospectivos , Programa de SEER , Estados Unidos/epidemiologia , Neoplasias Uterinas/mortalidade
6.
Arch Gynecol Obstet ; 299(6): 1641-1649, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30824986

RESUMO

OBJECTIVE: To examine the effectiveness of pegylated liposomal doxorubicin (PLD) maintenance therapy (intravenous administration at dose 40 mg/m2 on day 1, repeated every 4 weeks) after first-line salvage chemotherapy for platinum-sensitive recurrent epithelial ovarian cancer. METHODS: This retrospective cohort study examined women with a first recurrence of platinum-sensitive epithelial ovarian cancer diagnosed between 2005 and 2015. Eligible cases had PLD maintenance following the first-line salvage chemotherapy (n = 28). Outcomes of interest included adverse events related to PLD maintenance therapy and survival outcome after the first recurrence. RESULTS: The median number of PLD maintenance cycles was 7.5 (range 2-26), and 11 (40%) women received ≥ 12 cycles. The median cumulative dose of PLD was 432.5 mg/m2 (range 120-1200 mg/m2). No women developed cardiotoxicity or secondary malignancies. There were 16 (57%) women who developed any grade of adverse events, including 3 (11%) women who developed grade 3 adverse events. There were no grade 4 adverse events. The most common adverse event was mucositis (n = 7, 25%). Dose reduction due to adverse events occurred in 14 (50%) women including 3 (11%) women with discontinuation due to toxicity. Median progression-free survival and overall survival after the initiation of PLD maintenance was 14.5 months (2-year rate 21.1%) and 51.2 months (5-year rate 43.4%), respectively. CONCLUSION: Our study suggests that PLD maintenance therapy for platinum-sensitive recurrent ovarian cancer is relatively well tolerated with the use of dose reduction to manage toxicity. Our study suggests that PLD maintenance therapy may be effective for women with platinum-sensitive recurrent epithelial ovarian cancer.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Doxorrubicina/análogos & derivados , Recidiva Local de Neoplasia/tratamento farmacológico , Platina/uso terapêutico , Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Platina/farmacologia , Polietilenoglicóis/farmacologia , Polietilenoglicóis/uso terapêutico , Estudos Retrospectivos
7.
Obstet Gynecol ; 133(2): 245-254, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30633128

RESUMO

OBJECTIVE: To analyze clinical prognostic factors for survival after recurrence of high-grade, advanced-stage ovarian-peritoneal-tubal carcinoma and to develop a nomogram to predict individual survival after recurrence. METHODS: We retrospectively analyzed patients treated in multicenter Gynecologic Oncology Group protocols for stage III and IV ovarian-peritoneal-tubal carcinoma who underwent primary debulking surgery, received chemotherapy with paclitaxel and a platinum compound, and subsequently developed recurrence. Prognostic factors affecting survival were identified and used to develop a nomogram, which was both internally and externally validated. RESULTS: There were 4,739 patients included in this analysis, of whom, 84% had stage III and 16% had stage IV ovarian carcinoma. At a median follow-up of 88.8 months (95% CI 86.2-92.0 months), the vast majority of patients (89.4%) had died. The median survival after recurrence was 21.4 months (95% CI 20.5-21.9 months). Time to recurrence after initial chemotherapy, clear cell or mucinous histology, performance status, stage IV disease, and age were significant variables used to develop a nomogram for survival after recurrence, which had a concordance index of 0.67. The time to recurrence alone accounted for 85% of the prognostic information. Similar results were found for patients who underwent second look laparotomy and had a complete pathologic response or received intraperitoneal chemotherapy. CONCLUSION: For individuals with advanced-stage ovarian carcinoma who recur after standard first-line therapy, estimated survivals after recurrence are closely related to the time to recurrence after chemotherapy and prognostic variables can be used to predict subsequent survival. CLINICAL TRIAL REGISTRATION: ClinialTrials.gov, NCT00002568, NCT00837993, NCT00002717, NCT01074398, and NCT00011986.


Assuntos
Carcinoma/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/mortalidade , Idoso , Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Nomogramas , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/uso terapêutico , Compostos de Platina/uso terapêutico , Estudos Retrospectivos , Estados Unidos/epidemiologia
8.
Oncology (Williston Park) ; 32(8): 418-20, 422-4, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30153322

RESUMO

The carboplatin/paclitaxel doublet remains the chemotherapy backbone for the initial treatment of ovarian cancer. This two-drug regimen, with carboplatin dosed using the Calvert formula, yielded convincing noninferior outcomes when compared with the prior, more toxic, regimen of cisplatin/paclitaxel. Carboplatin's dose-limiting toxicity is thrombocytopenia; however, when this drug is properly dosed and combined with paclitaxel, the doublet's cycle 1 dose in chemotherapy-naive women is generally safe. Carboplatin (unlike cisplatin) contributes minimally to the cumulative sensory neuropathy of paclitaxel, thus ensuring noticeable reversibility of neuropathy symptoms following completion of 6 cycles and only occasionally requiring cessation or substitution of the taxane. Paclitaxel is responsible for the hair loss associated with the carboplatin/paclitaxel doublet; preventive measures must be considered for patients who would otherwise refuse treatment. Several first-line phase III trials, as well as ongoing trials for which only preliminary results have been published, have fueled debates on the optimal dose and schedule; these have focused not only on weekly vs q3-weeks paclitaxel, but also on other modifications and the advisability of adding bevacizumab. Our view is that results of this doublet in the first-line treatment of ovarian cancer are driven primarily by carboplatin, given that ovarian cancer is a platinum-sensitive disease. Consequently, the roles of the accompanying paclitaxel dose and schedule and the addition of bevacizumab are currently unsettled, and questions regarding these issues should be decided based on patient tolerance and comorbidities until additional data are available.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Feminino , Humanos , Quimioterapia de Indução , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos
9.
Cancer Chemother Pharmacol ; 82(1): 55-63, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29704010

RESUMO

PURPOSE: To evaluate the outcomes of intraperitoneal chemotherapy (IP) compared with those of intravenous chemotherapy (IV) in patients with advanced ovarian cancer after neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) or primary debulking surgery (PDS). METHODS: Patients with advanced epithelial ovarian carcinoma treated with PDS or NACT and IDS from 2006 to 2015 were identified. Comparative statistics were used to evaluate covariates, and survival rates were calculated using the Kaplan-Meier method and compared with log-rank tests. RESULTS: Sixty-six patients received NACT followed by IDS with residual disease of ≤ 1 cm; 42 of these patients (63.6%) received IP therapy; and 24 patients (36.3%) had IV therapy only after IDS. The median progression-free survival (PFS) was 16.0 months in the IP group and 13.5 months in the IV group (p = 0.13). The estimated median overall survival (OS) was 64.0 months with IP and 50.0 months with IV (p = 0.44). During the same study period, 149 patients underwent optimal PDS after which 93 patients (62.4%) received IP and 56 patients (37.6%) were given IV chemotherapy. Patients after IP demonstrated improved survival outcomes when compared to patients after IV therapy. The median PFS was 28.0 months after IP and 16.5 months after IV (p = 0.0006), and the median OS was not reached for IP and 50.0 months after IV (p < 0.0001). CONCLUSIONS: Although IP chemotherapy after PDS is associated with improved survival, IP therapy after NACT and IDS, despite high rates of completion, may not have the same degree of survival advantage over IV therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário/patologia , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução , Esquema de Medicação , Feminino , Humanos , Injeções Intraperitoneais , Injeções Intravenosas , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Taxa de Sobrevida
10.
Gynecol Oncol ; 147(2): 243-249, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28807367

RESUMO

PURPOSE: We examined disparities in prognosis between patients with ovarian clear cell carcinoma (OCCC) and serous epithelial ovarian cancer (SOC). METHODS: We reviewed data from FIGO stage I-IV epithelial ovarian cancer patients who participated in 12 prospective randomized GOG protocols. Proportional hazards models were used to compare progression-free survival (PFS) and overall survival (OS) by cell type (clear cell versus serous). RESULTS: There were 10,803 patients enrolled, 9531 were eligible, evaluable and treated with platinum, of whom 544 (6%) had OCCC, 7054 (74%) had SOC, and 1933 (20%) had other histologies and are not included further. In early stage (I-II) patients, PFS was significantly better in OCCC than in SOC patients. For late stage (III, IV) patients, OCCC had worse PFS and OS compared to SOC, OS HR=1.66 (1.43, 1.91; p<0.001). After adjusting for age and stratifying by protocol and treatment arm, stage, performance status, and race, OCCC had a significantly decreased OS, HR=1.53 (1.33, 1.76; p<0.001). In early stage cases, there was a significantly decreased treatment effect on PFS for consolidative therapy with weekly Paclitaxel versus observation in OCCC compared to SOC (p=0.048). CONCLUSIONS: This is one of the largest analyses to date of OCCC treated on multiple cooperative group trials. OCCC histology is more common than SOC in early stage disease. When adjusted for prognostic factors, in early stage patients, PFS was better for OCCC than for SOC; however, in late-stage patients, OCCC was significantly associated with decreased OS. Finally, treatment effect was influenced by histology.


Assuntos
Adenocarcinoma de Células Claras/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Carboplatina/administração & dosagem , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Prognóstico , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida
11.
Ecancermedicalscience ; 10: 646, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27350791

RESUMO

Treatment with tumour necrosis factor (TNF) antagonists may lead to enhanced susceptibility to certain malignancies. In particular, an association is seen emerging between TNF antagonists and development of squamous cell carcinomas (SCCs) of the skin (in association with psoriasis), the oral cavity, and in the anogenital areas (possibly related to prior human papilloma virus infection). We present here a case of a 53-year old woman with a history of severe rheumatoid arthritis (RA), most recently treated with the TNF antagonist etanercept plus methotrexate, presented to our service after several months of increasing left pelvis and buttock pain. Evaluation with a computerised tomography (CT)-directed biopsy of a pelvic side wall mass revealed a metastatic SCC. On a fluorodeoxyglucose (FDG) positron-emission tomography (PET) an additional area of uptake was identified in the left posterior rectum corresponding to a 1 cm nodule palpable on digital exam. Colonoscopic biopsy revealed a basaloid SCC of the rectum as the likely primary site. Immunosuppression following TNF antagonist therapy may have given arise to this unrestrained neoplastic growth. It thereby underscores the need for an initial baseline study of risk factors and identification of patients who are at higher risk for development of a malignancy, in order to achieve a diagnosis at an early stage.

13.
Ecancermedicalscience ; 10: 613, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26823682

RESUMO

Occult endometrial cancer is occasionally discovered in women with Lynch syndrome undergoing risk-reducing hysterectomy. The case presented here demonstrates that preoperative endometrial sampling can help detect these occult cancers; however, there are currently no recommendations for this preoperative intervention. A 50-year-old woman with Lynch syndrome underwent endometrial sampling prior to planned risk-reducing hysterectomy and bilateral salpingo-oophorectomy. The endometrial biopsy demonstrated a serous endometrial cancer. The patient was counselled regarding the diagnosis and revised operative plan, which now included staging, prior to surgery. Although the prevalence of occult endometrial cancer at the time of risk-reducing surgery in women with Lynch syndrome remains unknown, preoperative endometrial sampling may allow for improved patient counselling and surgical planning in this population, and can help avoid a subsequent surgery for staging.

15.
Oncologist ; 19(12): 1229-30, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25361625

RESUMO

BACKGROUND: Transcatheter arterial chemoembolization (TACE) has been used to curtail tumor vasculature and delay tumor progression in hepatocellular carcinoma (HCC). We conducted a phase I trial to evaluate the efficacy and toxicity of thalidomide when combined with TACE in patients with advanced HCC. METHODS: Between June 2000 and November 2003, 56 patients with unresectable HCC and amenable to TACE were enrolled. The starting dose of thalidomide was 200 mg/day and was escalated every 2 weeks as tolerated to a maximum dose of 1,000 mg/day. Dose reductions and discontinuation were determined by toxicity. TACE was performed 4 weeks after initiation of thalidomide therapy and repeated as necessary. RESULTS: Overall, 47 and 55 patients were evaluable for response and toxicity, respectively; the median dose of thalidomide given was 200 mg/day. Three patients (6.38%) patients achieved complete responses, whereas 10 (21.3%) had partial responses, for an overall response rate of 27.7%, and 27 (57.5%) had stable disease. Median progression-free survival was 7 months (95% confidence interval [CI]: 5-10 months), and median OS was 21 months (95% CI: 16-28 months) (Fig. 1). Fatigue and lethargy (49.1%), constipation (47.3%), and nausea (43.6%) were common. Grade 3-4 toxicities consisted mostly of increased aspartate aminotransferase (43.6%) and elevated alanine aminotransferase (38.2%) (Table 1). CONCLUSION: Thalidomide and TACE were commonly associated with nonhematologic side effects, with fatigue and constipation being prominent. With a lack of clear therapeutic benefit, this combination is unlikely to be pursued for HCC.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Talidomida/administração & dosagem , Progressão da Doença , Feminino , Humanos , Masculino , Taxa de Sobrevida , Resultado do Tratamento
17.
Int J Gynecol Cancer ; 24(3): 488-95, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24457564

RESUMO

OBJECTIVE: The treatment of recurrent epithelial ovarian cancer (rEOC) remains a major challenge because of the development of platinum resistance. To identify treatment regimens associated with better outcomes in BRCA mutation carriers compared with patients with nonhereditary (NH) disease, we summarized the experience after chemotherapy treatment of rEOC in 1 institution and compared the outcome in BRCA mutation carriers versus NH subsets. METHODS: We retrospectively analyzed 256 patient records with rEOC who were treated with second-, third-, and fourth-line treatment with the usual sequential regimens consisting of either pegylated liposomal doxorubicin (PLD), taxanes, gemcitabine, or topotecan (alone or in combination with platinum) between 2002 and 2012 at our institution. The analysis of founder mutations in 8 hotspots was performed. The outcome in BRCA mutation carriers was compared with that of patients with NH disease. RESULTS: BRCA mutation carriers treated with PLD (with or without platinum) or with gemcitabine + platinum had improved progression-free survival (PFS) and a lower risk for disease progression (adjusted for age, line of treatment, and platinum sensitivity) compared with patients with NH disease. By contrast, treatment with taxanes (with or without platinum) or topotecan led to similar PFS in BRCA mutation carriers and in patients with NH disease. Under all treatment regimens, BRCA mutation carriers showed improved overall survival after adjusting for age, line of treatment, and platinum sensitivity. CONCLUSIONS: This single-institution experience provides indications of an enhanced benefit in PFS for BRCA mutation carriers compared with patients with NH disease across a number of drug regimens (PLD, platinum, or gemcitabine + platinum) regardless of platinum sensitivity and line of therapy.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma/genética , Genes BRCA1 , Genes BRCA2 , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/genética , Adulto , Idoso , Carcinoma/tratamento farmacológico , Carcinoma/mortalidade , Feminino , Humanos , Israel/epidemiologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
18.
Oncology (Williston Park) ; 26(10): 936-43, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23176005

RESUMO

"Targeted therapy" is becoming the centerpiece of current therapeutic strategies, and is often mentioned as the desirable direction for future progress. Why and how it is replacing past approaches in the management of solid tumors is the subject of this two-part overview. Here, in Part I, we describe areas where major inroads were initially achieved by targeting angiogenesis (central to the biology of renal cell carcinoma and hepatocellular cancer) and by unraveling pathways in the heterogeneous tumors of mesenchymal origin--spurred by the identification of c-Kit-activating mutations in gastrointestinal stromal tumors (GIST) and the regressions that ensued when tumors harboring these mutations were exposed to the tyrosine kinase inhibitor imatinib (Gleevec). More recently, the successes in the treatment of the notoriously refractory malignant melanoma via the targeting of a specific BRAF mutation and via immune activation represent an unprecedented achievement of this new therapeutic direction. For each cancer discussed in the first part of our overview, as well as in Part II, which will deal with more common cancers, we briefly cover the tumor biology, how targeting was achieved, the introduction of immune modulation or immune-conjugates, and the impact these therapies are having in the disease.


Assuntos
Tumores do Estroma Gastrointestinal/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Ensaios Clínicos como Assunto , Tumores do Estroma Gastrointestinal/metabolismo , Humanos , Neoplasias Renais/metabolismo , Neoplasias Hepáticas/metabolismo
19.
Eur J Cancer ; 48(15): 2361-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22541893

RESUMO

AIM: Trabectedin in combination with pegylated liposomal doxorubicin (PLD) improves progression-free survival (PFS) compared to PLD alone in recurrent ovarian cancer (J Clin Oncol 2010;28:3107-14). METHODS: Women, stratified by performance status (0-1 versus 2) and platinum sensitivity (platinum-free interval [PFI]<6 versus ≥ 6 months), were randomly assigned to receive PLD 30 mg/m(2) IV followed by a 3-h infusion of trabectedin 1.1mg/m(2) every 3 weeks or PLD 50mg/m(2) every 4 weeks. The study was powered to show a 33% increase in overall survival (OS) after 520 deaths had occurred. RESULTS: After a median follow-up of 47.4 months, there were 522 deaths among 672 subjects. The median OS for trabectedin+PLD and PLD arms was 22.2 and 18.9 months, respectively (hazard ratio [HR]=0.86; 95% confidence interval [CI]: 0.72-1.02; p=0.0835). An unexpected but significant imbalance in the PFI favouring the PLD arm (mean PFI: PLD=13.3 months, trabectedin+PLD=10.6 months) was identified. On the basis of this finding, an unplanned hypothesis generating analysis adjusting for the PFI imbalance and other prognostic factors suggested an improvement in OS associated with the trabectedin+PLD arm (HR=0.82; 95%CI: 0.69-0.98; p=0.0285). In another unplanned exploratory analysis, the subset of patients with a PFI of 6-12 months had the largest difference in OS (HR=0.64; 95%CI: 0.47-0.86; p=0.0027). CONCLUSIONS: The final OS analysis did not meet the protocol-defined criterion for statistical significance. Despite stratification on platinum sensitivity, there was an imbalance in mean platinum free interval that had an effect on OS.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doxorrubicina/análogos & derivados , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Carcinoma Epitelial do Ovário , Dioxóis/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Polietilenoglicóis/administração & dosagem , Análise de Sobrevida , Tetra-Hidroisoquinolinas/administração & dosagem , Trabectedina
20.
Oncology (Williston Park) ; 26(11): 1021-30, 1035, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23330341

RESUMO

This second article in our two-part series on targeted therapies in solid tumors covers the emergence of targeted therapies for the treatment of two common malignancies: lung cancer and breast cancer. In these two tumors, the identification of a promising target has led to successful preliminary applications, and eventually to further advances through drug development and the fine tuning of patient selection. As a result, the percentage of patients with breast or lung cancer who are benefiting from targeted agents has steadily increased, even if the majority are still treated with conventional cytotoxic regimens. We also review the latest therapeutic strategies for colorectal and gynecologic cancers--because these offer an instructive contrast. The curative regimens that have been developed for these two tumors--even those in more advanced stages--have included combinations of surgery and/or radiation with chemotherapy. The Cancer Genome Atlas has revealed complexities in the biology of these tumors that underscore the fact that reliance on selective DNA-damaging agents such as platinums, antimetabolites, and antimitotic agents will continue for some time. We conclude that the therapeutic progress that may arise from the study of molecular pathways will be due not only to the development of new targeted therapies, but also to a better understanding of older drugs developed empirically in the past. Taken together, these two types of advance illustrate the remarkable overall effect of modern cancer therapeutics' focus on tumor biology and tumor immunology.


Assuntos
Neoplasias/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Feminino , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias dos Genitais Femininos/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias/genética , Neoplasias/imunologia
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