RESUMO
OBJECTIVE: We previously reported the feasibility of short-term low-volume hydration in patients with advanced lung cancer who received cisplatin-based chemotherapy (Jpn J Clin Oncol 2013). We sought to determine the clinical usefulness of a more convenient hydration method, evaluating the safety and efficacy of shorter-term and lower-volume hydration. METHOD: Chemonaïve patients with advanced lung cancer who were ≤ 75 years and reserved an adequate renal function for cisplatin use (≥ 60 mg/m(2)) were eligible. An intravenously administered hydration of 1700 ml in ~3.5 h with 1500 ml of orally administered hydration was investigated. The primary endpoint was the proportion of patients without grade 2 or worse renal toxicity in the first cycle. RESULTS: A total of 45 patients were registered, all of whom were evaluable for renal toxicity. The median baseline creatinine score was 0.70 mg/dl, and the median cisplatin dose on day 1 was 75 mg/m(2). In the first cycle, one patient (2 %) developed grade 2 creatinine toxicity, and thus, the proportion of patients with less than grade 2 was 98 % (the lower limit of 95 % confidence interval; 93 %), which met the primary endpoint. Five patients (11 %) had grade 1 or greater nephrotoxicity, three of whom successfully recovered. The objective response rate was 24 % and median progression-free survival 5.8 months. CONCLUSION: This prospective study demonstrated the safety and efficacy of shorter-term lower-volume hydration.
Assuntos
Injúria Renal Aguda/prevenção & controle , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hidratação/métodos , Neoplasias Pulmonares/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente , Adulto , Idoso , Cisplatino/administração & dosagem , Creatinina/sangue , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Critérios de Avaliação de Resposta em Tumores SólidosRESUMO
OBJECTIVE: Cisplatin can induce severe renal toxicity. However, the degree and pattern of hydration that is most efficient at preventing it have scarcely been formally evaluated. We here performed a prospective feasibility study of cisplatin-based chemotherapy with short-term low-volume hydration in advanced lung cancer. METHODS: Chemo-naïve patients with advanced lung cancer and reserving renal function who were suitable for cisplatin use (≥60 mg/m(2) on Day 1) were eligible for this study. Two-and-a-half-liter hydration within â¼4.5 h was investigated. The primary end point was the proportion of patients who underwent cisplatin-based chemotherapy without any Grade 2 or more renal toxicity in the first cycle. RESULTS: A total of 46 patients were registered, all of whom were evaluable for renal toxicity. The median baseline creatinine score was 0.70 mg/dl and the median cisplatin dose on Day 1 was 80 mg/m(2). In the first cycle, none of the patients developed Grade 2 or more creatinine toxicity, which met the primary endpoint. Four patients (9%) had Grade 1 toxicity, with a median worst creatinine score of 1.19 mg/dl, but it disappeared rapidly. Creatinine toxicity was influenced by several clinical factors, including the performance status. Ten patients (22%) needed extra hydration during the first cycle, mainly due to gastrointestinal toxicity. However, all 10 were able to undergo further cycles of treatment. Thirty-two (86%) of the 37 patients who were assumed to be able to undergo further treatment at our institute received it in an outpatient setting. CONCLUSIONS: This study demonstrated prospectively the feasibility of short-term low-volume hydration.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Hidratação/métodos , Rim/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Insuficiência Renal/prevenção & controle , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores/sangue , Cisplatino/administração & dosagem , Creatinina/sangue , Esquema de Medicação , Estudos de Viabilidade , Feminino , Humanos , Japão , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal/sangue , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/diagnóstico , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: Whether bevacizumab enhances the effect of the epidermal growth factor receptor (EGFR) inhibitor gefitinib on EGFR mutant non-small cell lung cancers (NSCLCs) remains unknown. We conducted a phase II trial to investigate the efficacy and safety of gefitinib when combined with bevacizumab as first-line therapy in patients with advanced NSCLC harboring EGFR gene mutations. METHODS: In this trial, 42 patients with a performance status of 0 to 2 received gefitinib (250 mg/d) and bevacizumab (15 mg/kg, every 3 weeks). The primary end point of this study was the 1-year progression-free survival (PFS) rate. We assumed that a 1-year PFS rate of 55% would indicate potential usefulness and that a 1-year PFS rate of 40% would constitute the lower limit of interest. RESULTS: Forty-two patients were enrolled in the study with a median age of 73 (range 42-86) years. Activating EGFR gene mutations included exon 19 deletion (57%) and L858R point mutations in exon 21 (38%). The objective response rate was 73.8% and included two complete responses. The 1-year PFS rate and median PFS time were 56.7% (95% confidence interval [CI] 39.9-70.5) and 14.4 months (95% CI 10.1-19.2), respectively. The median PFS differed significantly between EGFR exon 19 deletion and the L858R point mutation (18.0 versus 9.4 months, respectively; p = 0.006). The median overall survival had not yet been reached. Severe adverse events included grade 3 skin rash (15%), hypertension (17%), aspartate transaminase/alanine aminotransferase elevation (17%), proteinuria (7%), intracranial hemorrhage (2%), and grade 4 perforation of the digestive tract (2%). There were no treatment-related deaths. CONCLUSION: Gefitinib in combination with bevacizumab as first-line therapy seems to be a favorable and well-tolerated treatment for patients with advanced NSCLC with activating EGFR gene mutations, especially those with EGFR exon 19 deletion mutations, although the primary end point was not met because the lower limit of the CI was less than 40%.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Mutação/genética , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Gefitinibe , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Prospectivos , Quinazolinas/administração & dosagem , Taxa de SobrevidaRESUMO
BACKGROUND: We examined how crossover therapy might affect the association between progression-free survival (PFS) and overall survival (OS) in non-small cell lung cancer (NSCLC). METHODS: We extracted PFS- and OS-hazard ratios (HRs) in phase III trials of molecular-targeted agents for advanced NSCLC. Their relationship was modeled in a linear function with the coefficient of determination (R-squared) to assess the correlation between PFS and OS. RESULTS: Thirty-four trials with 35 pairs for the investigational and reference arms were identified (24,158 patients). Overall, there was little correlation between PFS- and OS-HRs (R-squared = 0.14), suggesting PFS-HR could account only for 14% of variation in OS-HR. The median proportion of crossover therapy per trial was 20%. If patients seldom crossed over (none or <1%), the association between PFS- and OS-HRs was strong (R-squared = 0.69). When the proportion of crossover was ≥1%, however, R-squared declined considerably (≥1% to <20% crossover, R-squared = 0.27; ≥20% to <40%, R-squared = 0.06; and ≥40%, R-squared = 0.27). CONCLUSIONS: A PFS advantage seldom is associated with an OS advantage any longer. Our analysis suggests this is due to a high level of crossover now that an increasing number of active agents are available for NSCLC.