RESUMO
Microsatellite instability(MSI)testing is performed in cancer patients to determine the indication for chemotherapy with immune checkpoint inhibitors. We report on our scheme to ensure that Lynch syndrome patients are offered the opportunity for genetic counseling and genetic testing. Two hundred and eight cancer patients(107 males and 101 females, 20- 87 years, mean 63.3 years)underwent MSI testing at our hospital between February 2019 and November 2021. From February 2019 to December 2020, the MSI testing was performed with a consent document that included a commentary on Lynch syndrome, and the results were explained only by the attending cancer doctors. Eleven(8.6%)of the 136 cases had MSI-high, but none of them led to a visit to the genetic medicine department. The Genome Center in our hospital, which was operational from April 2020, undertook information sharing by multiple professions and established a system to provide appropriate support to cancer doctors. Consecutively, 72 MSI tests were performed between January and November 2021, and 2 patients(2.8%)with MSI-high(1 with endometrial cancer and 1 with colorectal cancer)were referred to the Department of Clinical Genetics for genetic counseling. Through genetic testing, both were diagnosed with Lynch syndrome, and information on future surveillance and health care for blood relatives was provided.
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Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias do Endométrio , Masculino , Feminino , Humanos , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Instabilidade de Microssatélites , Testes Genéticos , Hospitais , Reparo de Erro de Pareamento de DNARESUMO
Olanzapine(OLZ)is a multi-acting receptor-targeted antipsychotic drug approved in Japan in December 2017 for the treatment of anticancer drug-induced nausea and vomiting. However, the recommended doses and administration periods of OLZ in the literature and guidelines are varied. Reports on the efficacy and safety of OLZ combined with perioperative chemotherapy for breast cancer in Japanese patients are few. Moreover, the risk of nausea and vomiting during treatment with anticancer drugs in young and women patients remains to be high. In this study, we conducted an exploratory survey on the optimal duration of OLZ administration(days 1-4: 5 mg, before sleep)during perioperative breast cancer 5-fluorouracil, epirubicin, cyclophosphamide(FEC)therapy. We found that treatment with OLZ showed efficacy in improving nausea grade and maintaining relative dose intensity. Moreover, it could be used safely without interruption due to side effects, such as weight gain, elevation in blood glucose, somnolence, and insomnia. Prophylactic antiemetic therapy with OLZ administration (days 1-4: 5 mg)prior to sleep was effective in patients having FEC therapy-induced nausea and vomiting.
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Antieméticos , Antineoplásicos , Neoplasias da Mama , Antieméticos/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/etiologia , Ciclofosfamida , Feminino , Humanos , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Náusea/prevenção & controle , Olanzapina/efeitos adversos , Olanzapina/uso terapêutico , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Vômito/prevenção & controleRESUMO
BACKGROUND: Current guidelines define primary and secondary endocrine resistance according to the periods of adjuvant endocrine therapy (adj-ET); however, the relationship between adj-ET period and endocrine resistance remains unclear. OBJECTIVE: We examined progression-free survival (PFS) after primary ET for recurrent hormone receptor-positive/HER2-negative breast cancer, and evaluated the relationship between endocrine resistance and the periods of adj-ET. METHODS: We assessed PFS among 183 patients who received ET as primary treatment for the first recurrence, according to the period of adj-ET (adj-ET < 1 year, 1-2 years, ≥2 years, and completion). RESULTS: Patients who relapsed during the first year of adj-ET had the significantly shortest PFS. PFS did not significantly differ between patients who relapsed at 1-2 years of adj-ET and patients who relapsed while on adj-ET but after the first 2 years. CONCLUSIONS: Relapse at 1-2 years after adj-ET initiation might be better classified as secondary endocrine resistance rather than primary endocrine resistance.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Hormônios/uso terapêutico , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/genética , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Adulto JovemRESUMO
Optimal treatment strategies for hormone receptor (HR)-positive, HER2-negative advanced and/or metastatic breast cancer (AMBC) remain uncertain. We investigated the clinical usefulness of adding capecitabine to maintenance endocrine therapy after induction chemotherapy and the efficacy of reinduction chemotherapy. Patients who had received bevacizumab-paclitaxel induction therapy and did not have progressive disease (PD) were randomized to maintenance therapy with endocrine therapy alone (group E) or endocrine plus capecitabine (1657 mg/m2/day on days 1-21, q4w) (group EC). In case of PD after maintenance therapy, patients received bevacizumab-paclitaxel reinduction therapy. Ninety patients were randomized. The median progression-free survival (PFS) under maintenance therapy (primary endpoint) was significantly longer in group EC (11.1 {95% CI, 8.0-11.8} months) than in group E (4.3 {3.6-6.0} months) (hazard ratio, 0.53; p < 0.01). At 24 months from the induction therapy start, the overall survival (OS) was significantly longer in group EC than in group E (hazard ratio, 0.41; p = 0.046). No difference was found in the time to failure of strategy (13.9 and 16.6 months in groups E and EC, respectively). Increased capecitabine-associated toxicities in group EC were tolerable. Addition of capecitabine to maintenance endocrine therapy may be a beneficial option after induction chemotherapy for HR-positive, HER2-negative AMBC patients.
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BACKGROUND: The initial therapeutic strategy for hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer is based on the first metastatic site; however, little evidence is available regarding the influence of metastatic distribution patterns of first metastatic sites on prognosis. In this study, we aimed to identify the metastatic distribution patterns of first metastatic sites that significantly correlate with survival after recurrence. METHODS: We performed a retrospective review of records from 271 patients with recurrent metastatic HR+/HER2- breast cancer diagnosed between January 2000 and December 2015. We assessed survival after recurrence according to the metastatic distribution patterns of the first metastatic sites and identified significant prognostic factors among patients with single and multiple metastases. RESULTS: Prognosis was significantly better in patients with a single metastasis than in those with multiple metastases (median overall survival after recurrence: 5.86 years vs. 2.50 years, respectively, p < 0.001). No metastatic organ site with single metastasis was significantly associated with prognostic outcome, although single metastasis with diffuse lesions was an independent risk factor for worse prognosis (HR: 3.641; 95% CI: 1.856-7.141) and more easily progressing to multiple metastases (p = 0.002). Multiple metastases, including liver metastasis (HR: 3.145; 95% CI: 1.802-5.495) or brain metastasis (HR: 3.289; 95% CI: 1.355-7.937), were regarded as significant independent poor prognostic factors; however, multiple metastases not involving liver or brain metastasis were not significantly related to prognosis after recurrence. CONCLUSIONS: Single metastases with diffuse lesions could more easily disseminate systemically and progress to multiple metastases, leading to a poor prognosis similar to multiple metastases. Our findings indicate that the reconsideration of the determinant factors of therapeutic strategies for first recurrence in HR+/HER2- breast cancer may be needed.
Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Recidiva Local de Neoplasia/mortalidade , Receptores de Estrogênio , Receptores de Progesterona , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Neoplasias da Mama/química , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/química , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/secundário , Prognóstico , Receptor ErbB-2 , Estudos RetrospectivosRESUMO
BACKGROUND: The original aim of this study was to evaluate the treatment sequence and anthracycline requirement in docetaxel, cyclophosphamide and trastuzumab therapy. After one death in the anthracycline-containing arm, the protocol was amended to terminate the randomization. The single-docetaxel, cyclophosphamide and trastuzumab arm was continued to examine the efficacy and safety of the anthracycline-free regimen. METHODS: Women with human epidermal growth factor receptor-2-positive, operable and primary breast cancer were randomized to receive 5-fluorouracil, epirubicin and cyclophosphamide (four cycles) followed by docetaxel, cyclophosphamide and trastuzumab (four cycles), or docetaxel, cyclophosphamide and trastuzumab followed by 5-fluorouracil, epirubicin and cyclophosphamide, or docetaxel, cyclophosphamide and trastuzumab (six cycles). After the protocol amendment, patients were allocated to the docetaxel, cyclophosphamide and trastuzumab arm alone. The primary endpoint was a pathological complete response. RESULTS: In total, 103 patients were enrolled between September 2009 and September 2011: 21, 22 and 24 patients in the 5-fluorouracil, epirubicin and cyclophosphamide followed by docetaxel, cyclophosphamide and trastuzumab; docetaxel, cyclophosphamide and trastuzumab followed by 5-fluorouracil, epirubicin and cyclophosphamide and docetaxel, cyclophosphamide and trastuzumab arms, respectively, and 36 patients in the docetaxel, cyclophosphamide and trastuzumab arm after the protocol amendment. In total, 60 patients were allocated to the docetaxel, cyclophosphamide and trastuzumab arm, in which the pathological complete response rate was 45.8%, and disease-free survival at 3 years was 96.6%. Patients with stage I or IIA in the docetaxel, cyclophosphamide and trastuzumab arm showed good disease-free survival (100% at 3 years). The comparison of efficacy among the three arms was statistically underpowered. Left ventricular ejection fraction decreased significantly after 5-fluorouracil, epirubicin and cyclophosphamide followed by docetaxel-docetaxel, cyclophosphamide and trastuzumab (P = 0.017), but not after docetaxel, cyclophosphamide and trastuzumab followed by 5-fluorouracil, epirubicin and cyclophosphamide or docetaxel, cyclophosphamide and trastuzumab. CONCLUSIONS: The pathological complete response rate for docetaxel, cyclophosphamide and trastuzumab was similar to previous reports of anthracycline-containing regimens. Docetaxel, cyclophosphamide and trastuzumab might be an option for primary systemic therapy in human epidermal growth factor receptor-2-positive early breast cancer. A larger confirmatory study is necessary.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Docetaxel/uso terapêutico , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapêutico , Adulto , Idoso , Antraciclinas/uso terapêutico , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Docetaxel/efeitos adversos , Epirubicina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Taxoides/uso terapêutico , Trastuzumab/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: We previously reported the synergistic effect of S-1 and eribulin in preclinical models. In addition, our phase I study revealed the recommended dose for the phase II study of the combination therapy in advanced breast cancer (ABC) patients pre-treated with anthracycline and taxane. Our current study reports on the efficacy and safety of the combined use of eribulin and S-1 in patients with ABC and poor prognosis. METHODS: Patients with breast cancer who received prior anthracycline- and/or taxane-based therapy were assigned to receive a combination therapy of eribulin (1.4 mg/m2 on days 1 and 8, every 21 days) and S-1 (65 mg/m2, on days 1 to 14, every 21 days) for advanced/metastatic disease. All patients had at least one clinicopathological factor such as being oestrogen receptor negative, Human Epidermal Growth Factor Receptor 2 (HER2) receptor negative, presence of visceral involvement, presence of three or more metastatic sites, or having a disease-free interval shorter than 2 years. The primary endpoint was the independent-reviewer assessed objective response rate (ORR). Secondary endpoints were clinical benefit rate, disease control rate, progression-free survival (PFS), and overall survival (OS). RESULTS: This study enrolled 33 patients. Confirmed ORR was 33.3% (95% CI: 17.3 to 52.8). Median PFS was 7.5 months (95% CI: 4.0 to 14.3). Median OS time was not reached during the current experimental periods. The most common grade 3/4 adverse event was neutropenia (68.8%). CONCLUSIONS: The combination of eribulin and S-1 is safe and effective for treatment in patients with ABC and poor prognosis. TRIAL REGISTRATION: Current Controlled Trials UMIN000015049 , date of registration: September 5th 2014.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Furanos/uso terapêutico , Cetonas/uso terapêutico , Ácido Oxônico/uso terapêutico , Tegafur/uso terapêutico , Adulto , Idoso , Antraciclinas/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Furanos/administração & dosagem , Furanos/efeitos adversos , Humanos , Cetonas/administração & dosagem , Cetonas/efeitos adversos , Pessoa de Meia-Idade , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Taxoides/uso terapêutico , Tegafur/administração & dosagem , Tegafur/efeitos adversosRESUMO
Cutaneous adverse events caused by aromatase inhibitors have been reported to be rare. We describe a rare case of a cutaneous adverse event that developed in a cancer-affected breast after aromatase inhibitor treatment. A 72-year-old postmenopausal female patient who was diagnosed with stage IA breast cancer received anastrozole as adjuvant treatment. Six months after the initiation of anastrozole, she developed an irregularly shaped purpuric plaque with several purpuric papules surrounding the postoperative scar on her left breast. Histological findings revealed capillary vessel proliferation and expansion, with hemorrhage in the superficial dermis. Immunohistochemistry of the skin biopsy specimen revealed hormone receptor expression limited to the vascular endothelial cells of the proliferating and expanding vessels. We believe that anastrozole induced a change in the local estrogen level, which affected the hormone receptor-positive endothelial cells in the dermis near the primary lesion of the breast cancer and caused a cutaneous adverse event only in the aforementioned area.
RESUMO
BACKGROUND/AIM: Little evidence is currently available on significant determinants of post-recurrence survival for patients with hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer. The objective of this study was to evaluate factors influencing post-recurrence survival in HR+/HER2-breast cancer. PATIENTS AND METHODS: A cohort of 236 patients with recurrent HR+/HER2- breast cancer was retrospectively analyzed to identify significant factors correlating with prognosis after recurrence. RESULTS: Multivariate analysis revealed independent prognostic factors of poor survival as follows: short intervals between recurrence and the end of adjuvant endocrine therapy (ET; p=0.046); short disease-free intervals (p=0.019); liver metastasis (p=0.007) or multiple metastases (p<0.001) at recurrence; and a poor response to first-line treatment (p<0.001). A poor first-line treatment response was significantly associated with a shorter response to a subsequent treatment line (p=0.007). Logistic regression analysis indicated that liver metastasis significantly increased the risk of a poor first-line-ET response (p=0.009). CONCLUSION: The first-line treatment response was the key to post-recurrence survival in patients with HR+/HER2- breast cancer. Particularly poor responses led to subsequent unfavorable prognostic outcomes.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Prognóstico , Adulto , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genéticaRESUMO
BACKGROUND/AIM: Patients with de novo stage IV and recurrent metastatic breast cancer are often treated with the same strategies, although the difference in prognostic outcomes remains unclear. The objective of this retrospective chart review study was to compare the prognostic outcomes between two types of patients with hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer. PATIENTS AND METHODS: We estimated overall survival of the two groups and evaluated the progressive course of the disease using disease-free interval (DFI) and interval from the end of adjuvant treatment to the first recurrence (AFI). RESULTS: We studied 172 patients with HR+/HER2- breast cancer, of which 65 were de novo and 107 were recurrent. Median OS between de novo and recurrent BC was 4.85 and 3.45 years, respectively (p=0.046). Recurrent patients with a DFI<2 years were found to have a significantly poorer prognosis than recurrent patients with a DFI≥2 years (p=0.016) and de novo patients (p=0.002). Similarly, recurrent patients with an AFI<1 year had a significantly poorer prognosis compared to de novo patients (p=0.026). CONCLUSION: De novo patients had better prognoses than recurrent patients with DFI<2 years or AFI<1 year, likely due to their therapy-naïve status or lower resistance to systemic treatment.
Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , RecidivaRESUMO
BACKGROUND: This phase II study was conducted to evaluate the efficacy and safety of the chemotherapy combination of gemcitabine and vinorelbine in taxane-pretreated Japanese metastatic breast cancer patients. METHODS: In this multicenter, phase II, single-arm study, patients with recurrent or metastatic HER2-negative breast cancer were administered gemcitabine (1,200 mg/m2) and vinorelbine (25 mg/m2) intravenously on days 1 and 8 every 3 weeks. The primary endpoint was the objective response rate, and other endpoints included progression-free survival, overall survival, and safety. RESULTS: A total of 42 patients were enrolled in this study. The objective response rate and clinical benefit rate were 24 and 43%, respectively. The median progression-free survival was 4.0 months. The median overall survival was 11.1 months. Grade 3/4 neutropenia was the most common hematologic toxicity, occurring in 22 patients (54%). Nonhematologic toxicity was moderate and transient, with fatigue (48%) being the most common condition and no severe adverse event reported. CONCLUSION: The combination of gemcitabine and vinorelbine is an effective and tolerable regimen for HER2-negative, taxane-pretreated, metastatic breast cancer patients in Japan.
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Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Vimblastina/análogos & derivados , Adulto , Idoso , Neoplasias da Mama/patologia , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Quimioterapia Combinada , Feminino , Humanos , Japão , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Neutropenia/etiologia , Prognóstico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Taxoides , Resultado do Tratamento , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Vinorelbina , GencitabinaRESUMO
BACKGROUND: The REGARD and RAINBOW trials showed that ramucirumab(RAM)alone and RAM plus paclitaxel(PTX) were effective therapies for advanced gastric cancer patients previously treated with chemotherapy. In this retrospective study, we evaluated the safety and efficacy of RAM alone and PTX plus RAM in such patients. METHODS: Patients who were received RAM at 8mg/kg or RAM plus PTX at 80mg/m2(on days 1, 8, and 15 of a 28-day cycle)between June 2015 and March 2016 were enrolled in this study. We compared the clinical outcome of RAM alone(RAM group, n=10)with that of RAM plus PTX(PTX+RAM group, n=13). RESULTS: The RAM group contained many more patients with poor performance status or prior chemotherapy of 2 or more regimens than the PTX+RAM group. All patients in both groups received chemotherapy on an outpatient basis. One case of grade 3 or 4 hematological adverse events was found in the RAM group and 6 cases were found in the PTX+RAM group. The overall response rate was 10% in the RAM group and 30% in the PTX+RAM group. Progression-free survival was 54 days in the RAM group and 187 days in the PTX+RAM group(p=0.0374). Overall survival was 158 days in the RAM group and was not reached in the PTX+RAM group(p=0.1091). CONCLUSIONS: RAM alone and RAM plus PTX can be administered safely on an outpatient basis and are beneficial for advanced gastric cancer patients previously treated with chemotherapy.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , RamucirumabRESUMO
Case 1: An 71-year-old man underwent chemotherapy with S-1 plus trastuzumab to treat type 3 gastric cancer that was diagnosed as Stage IV tubular adenocarcinoma(T4b[Panc], N3, H0, CY1, P0, M1). For anemia and active bleeding from the tumor, transcatheter arterial embolization(TAE)was performed with metallic coils on the splenic artery. Infarction of the spleen and left pleural effusion were observed. Second-line paclitaxel(PTX)chemotherapy was administered 4 weeks after TAE. Case 2: An 76-year-old man underwent chemotherapy with S-1 plus cisplatin to treat type 3 gastric cancer that was diagnosed as Stage IV tubular adenocarcinoma(T4a, N3, H0, P1, M1). For anemia and active bleeding from the tumor, TAE with gelatin sponge(Serescure®)was performed on the left and right gastric artery. Radiotherapy(31 Gy)with S-1 was performed because TAE was not effective for bleeding. After chemoradiotherapy, nab-PTX was administered. Case 3: An 74- year-old man underwent second-line chemotherapy with nab-PTX to treat type 4 advanced gastric cancer that was diagnosed as Stage IV tubular adenocarcinoma(T4a, N3, H1, P0, M1). For progression of anemia due to tumor bleeding, TAE with gelatin sponge(Serescure®)was performed on the left gastric artery. TAE was effective, and he was discharged from the hospital. In 2 of 3 cases, hemostasis was achieved by TAE. Therefore, TAE is effective to decrease bleeding from gastric cancer during chemotherapy.
Assuntos
Hemorragia/etiologia , Neoplasias Gástricas/terapia , Idoso , Embolização Terapêutica , Evolução Fatal , Humanos , Masculino , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologiaRESUMO
An 80-year-old man was admitted to our hospital with appetite loss in December 2014. Gastroduodenal scope, abdominal computed tomography(CT), and laparoscopy revealed type 4 advanced gastric cancer(poorly differentiated adenocarcinoma) with multiple lymph node(LN)involvement and multiple peritoneal metastasis. S-1(80mg/body)was administrated between January 2015 and September 2015 in the outpatient clinic. A partial response was obtained, but a gastric tumor, ascites, and LN re-growth were observed. Since October 2015, paclitaxel(PTX)(70mg/m2; day 1, 8, and 15)and ramucir- umab(RAM)(8mg/kg; day 1 and 15)have been administered. After 2 courses, bi-weekly PTX plus RAM were continued for grade 3 neutropenia and grade 2 anorexia. The tumor and LNs partially responded, and the ascites disappeared. With this dosage and administration schedule, the partial response(PR)was maintained for approximately 8 months without any severe adverse reactions. This successful case might indicate that it is important for elderly patients with gastric cancer that progressed with prior chemotherapy regimens to consider appropriate reduction of the PTX dosage, schedule, and continuation of RAM.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Humanos , Masculino , Paclitaxel/administração & dosagem , Neoplasias Gástricas/patologia , Resultado do Tratamento , RamucirumabRESUMO
PURPOSE: This phase I trial assessed afatinib, an irreversible ErbB family blocker, plus vinorelbine in Japanese patients with advanced solid tumors not amenable to standard treatment. METHODS: Primary objectives were evaluation of safety and the maximum tolerated dose (MTD) of once-daily (QD) afatinib plus weekly intravenous vinorelbine. Secondary objectives included pharmacokinetic assessments and preliminary efficacy. Dose finding utilized a 3 + 3 design, with a starting dose of afatinib 20 mg QD plus vinorelbine 25 mg/m(2) weekly. RESULTS: Seventeen patients were enrolled. Dose level 2 (afatinib 40 mg and vinorelbine 25 mg/m(2)) exceeded the MTD; dose-limiting toxicities (DLTs) were considered vinorelbine-related. Dose finding continued with modified dose levels; dose level 2a: afatinib 40 mg and a reduced dose of vinorelbine 20 mg/m(2) and dose level 3: afatinib 40 mg and vinorelbine 25 mg/m(2) allowing omission of vinorelbine for grade ≥2 neutropenia/thrombocytopenia and afatinib dose modification for adverse events (AEs). At dose level 3, 1/6 patients had a DLT (upper abdominal pain requiring afatinib dose reduction). Overall, the most frequent treatment-related AEs (any/grade 3 and 4) were: neutropenia (100/71 %), leukopenia (100/59 %), diarrhea (94/0 %), anemia (71/12 %) and stomatitis (65/0 %). Two patients with breast cancer achieved a partial response; eight patients (various cancer indications) had stable disease. Pharmacokinetic analyses suggested no relevant drug-drug interactions. CONCLUSIONS: Afatinib 40 mg QD plus vinorelbine 25 mg/m(2) weekly was tolerated in Japanese patients when dose modifications for known AEs for either compound were allowed. Tumor shrinkage was also observed. This dose schedule was recommended for phase II/III trials in Japanese patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Receptores ErbB/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Quinazolinas/efeitos adversos , Vimblastina/análogos & derivados , Adulto , Afatinib , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Estudos de Coortes , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Feminino , Humanos , Japão , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/patologia , Pacientes Desistentes do Tratamento , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/administração & dosagem , Quinazolinas/farmacocinética , Quinazolinas/uso terapêutico , Carga Tumoral/efeitos dos fármacos , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/farmacocinética , Vimblastina/uso terapêutico , VinorelbinaRESUMO
The CLEOPATRA trial showed a significant improvement in the progression-free survival (PFS) and overall survival of patients with HER2-positive first-line metastatic breast cancer (MBC) who were treated with pertuzumab (PER), trastuzumab (TRA), and docetaxel (DTX), compared to those treated with placebo, TRA, and DTX. PER was approved in 2013 for treating HER2-positive MBC in Japan. Herein, we present the retrospective review of data from 10 HER2-positive MBC patients who received PER in our hospital between September 2013 and August 2014.T he median age was 52 years (range, 45-66 years), and 7 patients were positive for ER.Six patients had not received any previous chemotherapy for their metastatic disease, while the others had received comparatively heavy pretreatment doses of chemotherapy.Our patients received the PER, TRA, and DTX regimen, although 2 patients were treated without DTX. Four patients experienced a partial response, 6 patients experienced stable disease (SD), and 3 patients experienced SD for ≥6 months. The response rate was 40%, and the clinical benefit rate was 70%.The median PFS was 7.3 months (range, 2.5-11.5 months). Grade 3 neutropenia and allergic reactions were observed in 1 and 2 patients, respectively; no Grade 4 adverse events were observed, and thus, the regimen was well tolerated. Further clinical research seems to be warranted for developing new treatment strategies involving PER for HER2-positive MBC.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Receptor ErbB-2/metabolismo , RecidivaRESUMO
BACKGROUND: The prognosis of breast cancer patients with brain metastasis (BM) is extremely poor, and the survival after development of BM is very short. We aimed to investigate clinicopathological factors related to significant effects on the prognosis after BM development. PATIENTS AND METHODS: This is a retrospective study of 75 early breast cancer patients who received the standard of care and subsequently developed BM. RESULTS: Breast cancer subtype was one of the significant predictors for prognosis after BM diagnosis. Luminal HER2 patients had the most favorable prognosis after BM diagnosis (p = 0.011). Favorable performance status (PS) at BM diagnosis (p < 0.001) and a single metastatic brain tumor (p = 0.032) were significantly associated with good prognosis after BM diagnosis. Metastatic time courses of the patients was found not to be significantly associated with survival after BM diagnosis. Univariate and multivariate analysis indicated that luminal HER2 cancer, favorable PS at BM diagnosis, and a single metastatic brain tumor were the independent prognostic factors for survival after BM development, making a decisive influence on local or systemic control. CONCLUSION: Appropriate treatments for tumor subtypes and to improve the general condition of patients would result in improved outcomes for the patients with BM.
RESUMO
Self-expanding metallic stents (SEMS) are a useful palliative option in malignant colorectal obstruction. The aim of this study was to evaluate the clinical outcomes of SEMS used for palliation. Patients with malignant colorectal obstruction who underwent SEMS insertion in our hospital from April 2014 to March 2015 were enrolled in the study. Clinical outcomes and complications of palliative SEMS insertion were retrospectively analyzed. Nine patients were enrolled in the palliative SEMS group. The success rate was 100%, while the complication rate was 11%. Successful SEMS insertion may enable oral intake in a few days, but 3 patients required up to several weeks to resume oral intake. Palliative SEMS are effective and beneficial for malignant colorectal obstruction.
Assuntos
Neoplasias Colorretais/complicações , Obstrução Intestinal/terapia , Cuidados Paliativos , Stents Metálicos Autoexpansíveis , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Obstrução Intestinal/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Qualidade de Vida , Resultado do TratamentoRESUMO
A woman in her 50s underwent distal gastrectomy and D1+b dissection in December 2005 for early gastric cancer that was diagnosed as a signet-ring-cell carcinoma, fStage â ¡ (T1a, N2, H0, P0, CY0, M0) with 12 lymph node metastases in the second field. Multiple bone metastases were diagnosed on the basis of CT and bone scintigraphy findings and serum ALP elevation (2,743 IU/L) I n December 2010. Fourteen courses of S-1 plus CDDP and 4 mg of zoledronate were administered from January to September in 2011. Pancytopenia, D-dimmer elevation, myelocytes, and metamyelocytes were observed in October 2012, indicating she had bone marrow metastasis. She was treated with a transfusion, anti-DIC therapy, and paclitaxel. She died from gastric cancer in December 2012. We report a rare case of recurrence with bone metastasis from early gastric cancer. S-1 plus CDDP chemotherapy and zoledronate therapy is an effective treatments for multiple bone metastases from gastric cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Ósseas/secundário , Cisplatino/administração & dosagem , Combinação de Medicamentos , Feminino , Gastrectomia , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Ácido Oxônico/administração & dosagem , Recidiva , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagem , Fatores de TempoRESUMO
Case 1: A man in his 70's was being treated with chemotherapy for unresectable advanced gastric cancer. Blood transfusion, endoscopic intervention including argon plasma coagulation, and transcatheter arterial embolization (TAE) were all used to treat repeated tumor bleeding causing anemia, but controlling the bleeding was difficult. In order to control the hemorrhage, radiation therapy of 31 Gy/10 Fr to the cancer was administered. After receiving radiation therapy, the anemia stopped. Case 2: A man in his 70's considered an operation for advanced gastric cancer, but his cardiac performance was poor and it was impossible to perform an operation. We conducted radiation therapy of 39 Gy/13 Fr for the purpose of preventing bleeding from gastric cancer. After receiving radiation therapy, the anemia stopped. We believe that radiation therapy is effective to stop bleeding from gastric cancer.