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Purpose@#Immune checkpoint inhibitors (ICI) and targeted small-molecule drugs are mainstay elements of lung cancer chemotherapy. However, they are associated with development of pneumonitis, a rare, but potentially life-threatening event. We analyzed lung cancer patients treated with ICI to evaluate the effect of sequential therapeutic administration on the incidence of pneumonitis. @*Materials and Methods@#In this retrospective study, 242 patients were included. Serial radiologic findings taken during and immediately after ICI treatment were reviewed. Factors that increased pneumonitis and the relationship between peri-ICI chemotherapy and the development of pneumonitis were evaluated. @*Results@#Pneumonitis developed in 23 patients (9.5%); severe pneumonitis (grade ≥ 3) occurred in 13 of 23 patients (56%); pneumonitis-related death occurred in six. High-dose thoracic radiation (≥ 6,000 cGy) revealed a tendency toward high risk of pneumonitis (odds ratio, 2.642; 95% confidence interval, 0.932 to 7.490; p=0.068). Among 149 patients followed for ≥ 8 weeks after the final ICI dose, more patients who received targeted agents within 8-weeks post-ICI experienced pneumonitis (3/16, 18.8%) compared with patients who received cytotoxic agents (4/54, 7.4%) or no chemotherapy (4/79, 5.1%) (p=0.162). Targeted therapy was associated with earlier-onset pneumonitis than treatment with cytotoxic agents (35 vs. 62 days post-ICI, p=0.007); the resulting pneumonitis was more severe (grade ≥ 3, 100% vs. 0%, p=0.031). @*Conclusion@#Sequential administration of small-molecule targeted agents immediately after ICI may increase the risk of severe pneumonitis. The sequence of chemotherapy regimens that include ICI and targeted agents should be carefully planned to reduce the risk of pneumonitis in lung cancer patients.
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Purpose@#Squamous cell carcinomas (SqCC) of the lung often express high levels of thymidylate synthase (TS), which is associated with primary resistance to pemetrexed. We explored the efficacy of pemetrexed in a selected population of patients with lung SqCC with low TS expression. @*Materials and Methods@#In this single-arm phase II trial, we enrolled 32 previously-treated patients with advanced lung SqCC exhibiting low immunohistochemical staining for TS (i.e., in 10% or less of tumor cells). The primary endpoint was 12-week progression-free survival (PFS) rate. @*Results@#Of 32 patients, eight patients (25%) had an Eastern Cooperative Oncology Group performance status of 2, and seven patients (22%) had previously received three or more lines of chemotherapy. The disease control rate from pemetrexed treatment was 30%, and no objective response was observed. The 12-week PFS rate was 24.5% (95% confidence interval [CI], 13.0 to 46.1). Median PFS was 1.3 months (95% CI, 1.3 to 2.7), and median overall survival was 11.8 months (95% CI, 8.1 to not applicable). Most of adverse events were grade 1 or 2. @*Conclusion@#Pemetrexed demonstrated modest activity as a salvage chemotherapy in patients with advanced lung SqCC with low TS expression, although its toxicity was generally manageable.
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PURPOSE: Concurrent chemoradiotherapy (CCRT) is the standard care for stage III non-small cell lung cancer (NSCLC) patients; however, a more effective regimen is needed to improve the outcome by better controlling occult metastases. We conducted two parallel randomized phase II studies to incorporate erlotinib or irinotecan-cisplatin (IP) into CCRT for stage III NSCLC depending on epidermal growth factor receptor (EGFR) mutation status. MATERIALS AND METHODS: Patients with EGFR-mutant tumors were randomized to receive three cycles of erlotinib first and then either CCRT with erlotinib followed by erlotinib (arm A) or CCRT with IP only (arm B). Patients with EGFR unknown or wild-type tumors were randomized to receive either three cycles of IP before (arm C) or after CCRT with IP (arm D). RESULTS: Seventy-three patients were screened and the study was closed early because of slow accrual after 59 patients were randomized. Overall, there were seven patients in arm A, five in arm B, 22 in arm C, and 25 in arm D. The response rate was 71.4% and 80.0% for arm A and B, and 70.0% and 73.9% for arm C and D. The median overall survival (OS) was 39.3 months versus 31.2 months for arm A and B (p=0.442), and 16.3 months versus 25.3 months for arm C and D (p=0.050). Patients with sensitive EGFR mutations had significantly longer OS than EGFR-wild patients (74.8 months vs. 25.3 months, p=0.034). There were no unexpected toxicities. CONCLUSION: Combined-modality treatment by molecular diagnostics is feasible in stage III NSCLC. EGFR-mutant patients appear to be a distinct subset with longer survival.
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Humanos , Braço , Carcinoma Pulmonar de Células não Pequenas , Quimiorradioterapia , Cisplatino , Cloridrato de Erlotinib , Metástase Neoplásica , Patologia Molecular , Receptores ErbBRESUMO
PURPOSE: Paclitaxel (P) and gemcitabine (G) are clinically synergistic in small cell lung cancer (SCLC). We evaluated the efficacy of PG as a salvage treatment for SCLC patients whose disease progressed after a platinum-containing regimen. MATERIALS AND METHODS: Eligibility included histologically confirmed SCLC, one dimensionally measurable disease, Eastern Cooperative Oncology Group performance status 0-2, and progressive disease after platinum-based chemotherapy. Treatment consisted of P (80 mg/m2) and G (1,000 mg/m2) on days 1 and 8 of each cycle of 21 days until disease progression. RESULTS: Thirty-three patients seen between December 2005 and February 2009 were selected into this study. Thirty patients (91%) had received irinotecan-platinum, and three had received etoposide-platinum. Sixteen patients (49%) had a treatment-free interval of less than 3 months. The overall response rate was 30.3% (29.4% in sensitive relapse and 31.3% in refractory relapse). The median time to progression was 12.0 weeks and median overall survival (OS) 31.0 weeks, with a 1-year OS rate of 30.3%. Toxicities were moderate and manageable with 18.2% grade (G) 4 neutropenia, 24.2% G3 thrombocytopenia, 6.1% G3 sensory neuropathy, and 3% G3 asthenia. One patient developed febrile neutropenia. CONCLUSION: Second-line paclitaxel and gemcitabine were well-tolerated and moderately active in SCLC patients previously treated with platinum-based chemotherapy.
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Humanos , Astenia , Progressão da Doença , Tratamento Farmacológico , Neutropenia Febril , Neutropenia , Paclitaxel , Recidiva , Carcinoma de Pequenas Células do Pulmão , TrombocitopeniaRESUMO
Endovascular treatment (EVT) including angioplasty and stenting is an effective treatment for superior vena cava (SVC) syndrome. Recurrence of SVC syndrome is mainly caused by tumor progression and occurs in around 20% after EVT, but sometimes venous thrombosis within stent accounts for recurrence of SVC syndrome. Anticoagulation after EVT is still a controversial issue. In our case, a 73-year-old man with SVC syndrome caused by mediastinal metastasis from non-small cell lung cancer underwent endovascular stent followed by anticoagulation with low molecular weight heparin (LMWH), but symptomatic progression due to in-stent thrombosis necessitated the second procedure after two weeks. A total of 4 sessions of endovascular stent and anticoagulation with LMWH, warfarin and rivaroxaban did not induce durable resolution of in-stent thrombosis. Our case suggests refractory in-stent thrombosis could develop despite of anticoagulation after endovascular stent for SVC syndrome.
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Idoso , Humanos , Angioplastia , Carcinoma Pulmonar de Células não Pequenas , Heparina de Baixo Peso Molecular , Metástase Neoplásica , Recidiva , Rivaroxabana , Stents , Síndrome da Veia Cava Superior , Trombose , Veia Cava Superior , Trombose Venosa , VarfarinaRESUMO
Most patients with tyrosine kinase inhibitor (TKI)-sensitive non-small cell lung cancer (NSCLC) eventually develop acquired resistance to TKIs. Factors that affect TKI-sensitive patient survival after progression during TKI treatment remain unknown. We attempted to identify factors that affected post-progression survival. We retrospectively reviewed 81 advanced NSCLC patients with disease progression following tumor response and durable (> or = 6 months) disease stabilization with first-line or second-line gefitinib. Post-progression survival (PPS) and characteristics were investigated and compared in patients who did (n = 16) and did not (n = 65) resume TKIs. Most patients were female never-smokers with adenocarcinoma. Median overall PPS was 10.3 months (95% confidence interval [CI], 7.458-13.142). Age, gender, smoking history, histology, Eastern Cooperative Oncology Group performance status at gefitinib initiation, initial stage, and platinum-based chemotherapy after gefitinib were not significant predictors of PPS. Pemetrexed use after gefitinib significantly improved PPS (18.5 vs 8.6 months; hazard ratio [HR], 0.45; P = 0.008). Gefitinib reuse tended to lengthen PPS but was insignificant in multivariate analysis (27.4 vs 8.8 months; HR, 0.53; P = 0.095). NSCLC patients assumed to have clinically acquired resistance to TKIs had relatively long PPS. TKIs reuse or pemetrexed use after progression with gefitinib may improve PPS.
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Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Glutamatos/uso terapêutico , Guanina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Estudos Retrospectivos , Sobrevida , Resultado do TratamentoRESUMO
Tumor associated microtubule associated protein (TMAP), also known as cytoskeleton associated protein 2 (CKAP2) is a mitotic spindle-associated protein whose expression is cell cycle-regulated and also frequently deregulated in cancer cells. Two monoclonal antibodies (mAbs) against TMAP/CKAP2 were produced: B-1-13 and D-12-3. Interestingly, the reactivity of mAb D-12-3 to TMAP/CKAP2 was markedly decreased specifically in mitotic cell lysate. The epitope mapping study showed that mAb D-12-3 recognizes the amino acid sequence between 569 and 625 and that phosphorylation at T596 completely abolishes the reactivity of the antibody, suggesting that the differential reactivity originates from the phosphorylation status at T596. Immunofluorescence staining showed that mAb D-12-3 fails to detect TMAP/CKAP2 in mitotic cells between prophase and metaphase, but the staining becomes evident again in anaphase, suggesting that phosphorylation at T596 occurs transiently during early phases of mitosis. These results suggest that the cellular functions of TMAP/CKAP2 might be regulated by timely phosphorylation and dephosphorylation during the course of mitosis.
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Animais , Humanos , Camundongos , Sequência de Aminoácidos , Anticorpos Monoclonais/metabolismo , Ciclo Celular/fisiologia , Células Cultivadas , Proteínas do Citoesqueleto/química , Mapeamento de Epitopos , Células HeLa , Mitose/fisiologia , Dados de Sequência Molecular , Fosforilação , Proteínas Serina-Treonina Quinases/metabolismo , Homologia de Sequência de Aminoácidos , Treonina/metabolismoRESUMO
PURPOSE : To evaluate the compliance of patients who underwent complete resection of non-small cell lung cancer (NSCLC) with adjuvant chemotherapy. MATERIALS AND METHODS : Between January 2004 and May 2006, patients who underwent a complete resection for NSCLC were referred to oncologists for adjuvant chemotherapy. Three or 4 cycles of platinum-based adjuvant chemotherapy was then performed according to the protocol or the preference of the oncologists. RESULTS : Two hundred and thirty-two patients were enrolled in this study. The median age of the study group was 60.9 years and 76.7 % of the patients enrolled were male. 34.9%, 28.8% and 36.2% of the patients were in stage IB, II and III respectively. In addition, 142 of the patients (61.2%) completed all planned cycles, whereas 65 patients (28%) received no therapy. The causes of start failure for adjuvant chemotherapy consisted of decreased postoperative performance status (n=39), refusal (n=13) and distant metastasis at the initial follow-up (n=2). The causes of cessation during adjuvant chemotherapy included the occurrence of severe adverse effects (n=12), aggravation of the disease with newly developed metastasis (n=4) and others (n=6). The mortality related to the adjuvant chemotherapy was 1.3 % (n=3), all of the fatalities were due to pneumonia and sepsis. Univariate analysis showed that age, postoperative complications and pathologic staging were the significant factors that determined whether the adjuvant chemotherapy was completed. Multivariate analysis demonstrated statistically significant differences in compliance when age and pathologic staging were considered. CONCLUSION : Adjuvant chemotherapy for completely resected NSCLC was performed with satisfactory compliance in approximately 60% of the patients included in this study, and age plays an important role in the compliance of adjuvant chemotherapy. Elderly subsets will be examined to help determine the effect of age on compliance and outcome. In addition, the medical oncologist tended to complete the adjuvant chemotherapy for more advanced cases of lung cancer than for stage IB lung cancer
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Idoso , Humanos , Masculino , Carcinoma Pulmonar de Células não Pequenas , Quimioterapia Adjuvante , Complacência (Medida de Distensibilidade) , Dissulfiram , Tratamento Farmacológico , Seguimentos , Neoplasias Pulmonares , Mortalidade , Análise Multivariada , Metástase Neoplásica , Pneumonia , Complicações Pós-Operatórias , SepseRESUMO
BACKGROUND: The role of second-line chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC) is known to be limited. Recently, ZD1839, the small molecule epidermal growth factor receptor-tyrosine kinase inhibitor, has been developed and has shown anti-tumor activity in patients with solid malignant tumors including lung cancer. We evaluated the response rate and toxicities of ZD1839 in patients with advanced NSCLC which has progressed after previous chemotherapy. PATIENTS AND METHODS: We examined 83 patients with advanced NSCLC treated with ZD1839 for more than 1 month in Korea Cancer Center Hospital during the period from January 2002 to September 2003. All the patients were enrolled in the international expanded access program (EAP) with ZD1839 by AstraZeneca. The administered dose of ZD1839 was 250 mg once daily. Chest radiography and laboratory tests were followed-up. We evaluated the response rate, median survival, and toxicity after treatment. RESULTS: Median age of the patients was 59 years (range 33-76). The most predominant cell type was adenocarcinoma and the most stage of the patients was IV. ECOG performance status was as follows; grade 0-1 in 10, grade 2 in 42, and grade 3 in 31 patients. Partial response was achieved in 12 patients (14.5%). Median overall survival was 9.2 (range 1.3-21.6+) months and median time to progression was 3.1 (range 1-21.2+) months. The most common adverse effect of ZD1839 was skin eruption which developed in 25 patients (25.8%). Significantly higher response rate and survival was found in patients with adenocarcinoma or good performance status. CONCLUSION: ZD1839 showed modest activity and tolerable toxicity in the treatment for patients with NSCLC which has progressed after previous chemotherapy.
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Humanos , Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Tratamento Farmacológico , Fator de Crescimento Epidérmico , Coreia (Geográfico) , Neoplasias Pulmonares , Fosfotransferases , Radiografia , Pele , Carcinoma de Pequenas Células do Pulmão , TóraxRESUMO
PURPOSE: Accurate assessment of the lesion after treatment of patients with bone lymphoma is difficult. In this patient who demonstrated complete remission after chemotherapy, the regions of fluorine-18 fluorodeoxyglucose ( (18) FFDG) PET uptake diminished more rapidly following therapy, indicating a complete response at much earlier stage than did Magnetic Resonance Imaging (MRI) or CT based findings. With the conventional methods, such as MRI and CT, it was difficult to assess whether the residual tumor tissue was viable or not. Decision to complete response is very important in patients with lymphoma to plan the further treatment. We experienced a patient with primary lymphoma of bone who revealed complete response to chemotherapy on (18) FFDGPET while CT showed persistent destructive bone lesion. Thus, (18) FFDGPET study after therapy may be superior to CT in the evaluation of response to treatment in primary lymphoma of bone.
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Humanos , Tratamento Farmacológico , Elétrons , Fluordesoxiglucose F18 , Linfoma , Imageamento por Ressonância Magnética , Neoplasia Residual , Tomografia por Emissão de PósitronsRESUMO
BACKGROUND: Flow cytometric measurement of DNA can reveal G0/G1, S, G2/M phases of cell cycle, and BrdU labeling can determine the percentage of cells in active DNA synthesis. A monoclonal antibody (MoAb), Ki-67, recognizes a protein that is present only in the nucleus of cycling cells but absent in resting cells. We analyzed whether the resting and the proliferating fraction could be differentiated by double staining with Ki-67 MoAb and propidium iodide (PI), and observed the effects of GM-CSF on cell cycle in acute myelogenous leukemia (AML) cells by Ki-67 MoAb. METHODS: Blast cells were prepared from 9 AML patients. The cells were incubated for 48 hours with or without GM-CSF. Cells were stained with BrdU/PI and Ki-67/PI. Cell cycle was analyzed by flow cytometry. RESULTS: The average fraction of G0/G1, S, and G2/M phases was 84.6%, 10.9%, and 4.5 % by BrdU/PI and 87.8%, 8.6%, and 3.7% by Ki-67/PI, respectively. Ki-67/PI staining dis-criminated between G0 and G1 phases and the average was 71.5% and 16.3%, respectively. In cells incubated with GM-CSF, BrdU/ PI method showed that the average S phase fraction (SPF) significantly increased from 10.9 to 16.2% (P=0.01) and the fraction of G0/G1 phase decreased from 84.6% to 78.4% (P= .02). Ki-67/PI method showed that the median SPF significantly increased from 8.6% to 13.7% (P=0.05) and G0 fraction decreased from 71.5% to 58.1% (P=0.02) but G1 fraction increased from 16.3% to 22.3% (P=0.01). CONCLUSION: Cell cycle analysis by Ki-67 MoAb and PI in AML is rapid and simple. It is especially useful to determine the growth fraction and G0 fraction compared to BrdU/PI staining.
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Humanos , Bromodesoxiuridina , Ciclo Celular , DNA , Citometria de Fluxo , Fase de Repouso do Ciclo Celular , Fase G1 , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Antígeno Ki-67 , Leucemia Mieloide Aguda , Propídio , Fase SRESUMO
No abstract available.
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Humanos , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Granulócitos , Macrófagos , MetotrexatoRESUMO
Cervical cancer is the most common gynecologic cancer, accounting for 22.2% of all cancers in Korean women and is almost of squamous cell type. The reported incidence of adenocarcinoma of the uterine cervix varies from 4 to 20% of all cervical malignancies, and have shown an increase in the percentage of adenocarcinoma. Adenocarcinoma may have a slightly poorer prognosis than squamous cell carcinoma for each stage of disease. Pulmonary metastases are observed in 2~9% of patients and correlates with stage of disease. We report a case of cervical adenocarcinoma with pulmonary metastases simulating miliary tuberculosis. These metastases was confirmed by open lung biopsy.
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Feminino , Humanos , Adenocarcinoma , Biópsia , Carcinoma de Células Escamosas , Colo do Útero , Incidência , Pulmão , Metástase Neoplásica , Prognóstico , Tuberculose Miliar , Neoplasias do Colo do ÚteroRESUMO
The incidence of acute leukemia in pregnancy is rare. The treatment of acute leukemia during pregnancy is complicated and therapeutic options must be made with each individual patient. Complete remission can now be achieved in 60 to 70% of previously untreated adults with acute myelogenous leukemia (AML). Antileukemic chemotherapy can be administered safely during the second and third trimesters. Cytarabine (ara-C) and anthracycline has not been associated with birth defect. When a pregnant woman presents with acute leukemia, chemotherapy should be recommended as vigorously as in the non- pregnant woman. We reported a case of AML during pregnancy. The patient recieved induction chemotherapy with ara-C and idarubicin. The baby was delivered at 33 weeks of gestation and had transient neutropenia. The mother received consolidation chemotherapy after achievement of complete remission.