RESUMO
BACKGROUND: Anti-angiogenic agents are reported to exert clinical activity in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). We evaluated the outcomes of the combination of docetaxel plus nintedanib in refractory NSCLC patients harboring EGFR mutations. METHODS: We retrospectively analyzed 19 patients with advanced EGFR-mutant NSCLC who had progressed to EGFR tyrosine kinase inhibitors (TKI) and platinum-based chemotherapy receiving docetaxel and nintedanib at 14 Spanish institutions from January 2013 to December 2019. Kaplan-Meier and log-rank tests were used to evaluate progression-free survival (PFS) and overall survival (OS). RESULTS: Median age was 58.9 years (range 42.8-81), 73.7% were female. All patients were Caucasian, and 73.7% were never or light smokers. The baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0-1 in 94.7% of patients. All patients had adenocarcinoma. Brain and liver metastases were present in 47.4% and 31.6% of patients, respectively. The most common EGFR mutations were exon 19 deletion (52.6%) and exon 21 L858R mutation (36.8%); 47.4% patients presented the EGFR T790M. 94.8% of the patients had received 2-3 previous treatment lines. Docetaxel was administered at 75 mg/m2/3 weeks to 16 patients, at 60 mg/m2 to 2 patients and at 45 mg/m2 to one patient. Nintedanib was given until disease progression or unacceptable toxicity at 200 mg twice daily except in 2 patients who received 150 mg twice daily and one patient who received 100 mg/12 h. With a median follow-up of 11.4 months (1-38), the median PFS was 6.1 months [95% confidence interval (CI), 4.9-7.3] and the median OS 10.1 months (95% CI 5.9-14.3). The objective response rate (ORR) was 44.4% (23.7-66.8%) and the disease control rate (DCR) 72.2% (49.4-88.5%). Efficacy tended to be greater in patients with the acquired T790M who had received osimertinib, with a median PFS of 6.3 (95% CI 2.1-10.5) versus (vs.) 4.8 (95% CI 3.5-6.1) and a median OS of 12.3 months (95% CI 8.6-16.0) vs. 6.7 months (95% CI 3.9-9.4), although this tendency was not statistically significant (p = 0.468 and p = 0.159, respectively). Sixteen patients (84.2%) had a total of 34 adverse events (AEs), with a median of two (0-6) AEs per patient. The most frequent AEs were asthenia (20.6%) and diarrhea (20.6%). One treatment-related death due to portal thrombosis was reported. CONCLUSIONS: Our data indicate that the combination of docetaxel and nintedanib can be considered to be an effective treatment for EGFR TKI-resistant EGFR-mutant NSCLC.
Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Docetaxel/administração & dosagem , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Indóis/administração & dosagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
INTRODUCTION: Circulating endothelial cells (CEC) play an important role in tumor neovascularization and may have prognostic value in cancer patients. This study was designed to investigate the role of CEC as a marker for predicting platinum plus pemetrexed first-line chemotherapy efficacy in advanced non-squamous non-small cell lung cancer (NSCLC). METHODS: A prospective study was performed whose main objective was to study whether the numbers of CEC at baseline and prior to the second and third cycle of chemotherapy were response predictors. Sixty-nine patients received cisplatin plus pemetrexed, and peripheral blood samples were performed at baseline and after second and third cycle. Separation and CEC count were performed using inmunomagnetic separation (CellSearch). RESULTS: The CEC count in 4 mL of peripheral blood was obtained prior to the first, second, and third cycle of treatment. Baseline levels and evolution of CEC were correlated with response to treatment according to RECIST criteria after three cycles of treatment. Sixty-nine patients were included: 43 (64.2 %) received cisplatin/pemetrexed and 24 (35.8 %) carboplatin/pemetrexed. Range of baseline CEC: 8-965 (mean of 153 cel/4 mL). The results after 3 cycles were: 25 partial responses (36.2 %), 17 cases of stabilization of disease (24.6 %), 16 of progressive disease (23.2 %) and 11 non-evaluables (16 %). No significant relationship between the baseline CEC count and response was found (p value = 0.831). Increase >50 % between the first and second cycle was correlated significantly with progression disease (p = 0.008). Patients who had a baseline CEC count greater than the mean (>153 cells/4 mL) showed longer progression-free survival and global survival without statistical significance. CONCLUSIONS: In this homogeneous group of patients with NSCLC, there is no correlation between response to treatment and CEC baseline levels. The increase in CEC numbers after the first cycle could be a negative predictive factor.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Endotélio Vascular/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Feminino , Humanos , Separação Imunomagnética/métodos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Pemetrexede/administração & dosagem , Estudos Prospectivos , Resultado do TratamentoRESUMO
AIMS: The aim of this study was to assess the impact of adapted ice cream as a dietary supplement on the quality of life (QLQ) of malnourished patients with cancer. MATERIAL AND METHODS: We present an exploratory prospective observational study comparing two patterns of nutrition in cancer patients admitted during the study period who presented malnutrition disorders: adapted ice cream (Group I: 39 patients) and nutritional supplements (Group II: 31 patients). Patients were selected from two different hospitals from the same Oncologic Institute. QLQ was evaluated with the Hospital Anxiety and Depression Scale (HADS) and QLQ of the European Organization for Research and Treatment of Cancer (EORTC QLQ C30). Nutrition was determined by the PG-SGA test. RESULTS: HADS showed significant differences in anxiety (p = 0.023) and depression (p = 0.011) at the end of the study only in Group I. QLQ-C30 revealed statistically significant differences in baseline measures of global dimension between the two groups (Group I: 40.64-56.36 CI; Group II: 25.70-43.11 CI; p = 0.017). Differences were also present in the social dimension (Group I: 77.42-93.51 CI; Group II: 55.85-82.85 CI; p = 0.039). Statistically significant differences were observed between the two groups at the end of the study in the global scale: Group I had 49.36-63.88 CI and Group II had 33.05-51.88 CI (p = 0.016), and in the fatigue scale: Group I had 36.19-53.83 CI and Group II had mean = 65.87, 52.50-79.23 CI (p = 0.007). CONCLUSIONS: The administration of ice cream could cover, in part, the social aspect of food and improve QLQ in malnourished cancer patients. These results are encouraging and deserve further confirmation.