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Quality of life in a randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer.
Taira, N, Kashiwabara, K, Tsurutani, J, Kitada, M, Takahashi, M, Kato, H, Kikawa, Y, Sakata, E, Naito, Y, Hasegawa, Y, et al
Breast cancer (Tokyo, Japan). 2022;(1):131-143
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BACKGROUND To report our findings on quality of life (QoL) in a randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). METHODS Patients with HER2-negative MBC were randomly assigned to three different doses of q3w nab-PTX (SD 260 mg/m2 vs. MD: 220 mg/m2 vs. LD 180 mg/m2). QoL was assessed at baseline and during the second, fourth and sixth courses of treatment using the Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane), Cancer Fatigue Scale (CFS) and EuroQol 5-Dimension (EQ-5D). Comparisons were performed with mixed-model repeated measures (MMRM). RESULTS A total of 141 patients were enrolled in the parent study, and 136 (96%) (44, 45 and 47 in the SD, MD, and LD groups) were included in the analysis. MMRM analysis showed that the difference from the baseline FACT-Taxane trial outcome index at MD and LD were significantly higher than that at SD (MD vs. SD P < 0.001, LD vs. SD P < 0.001). Differences from baseline for FACT-Taxane total, physical and emotional well-being, and taxane subscale scores at MD and LD were also higher than at SD. The difference from baseline for the CFS score at LD was lower than at SD (P = 0.013) and those for EQ-5D utility scores at MD and LD were higher than at SD (MD vs. SD P = 0.011, LD vs. SD P < 0.001). CONCLUSION QoL of patients treated with 220 or 180 mg/m2 of q3w nab-PTX was significantly better than that of patients treated with 260 mg/m2. TRIAL REGISTRATION The protocol was registered at the website of the University Hospital Medical Information Network (UMIN), Japan (protocol ID: UMIN000015516), on 01/11/2014. Details are available at the following address: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017916.
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Effect of early tumor response on the health-related quality of life among patients on second-line chemotherapy for advanced gastric cancer in the ABSOLUTE trial.
Fujitani, K, Shitara, K, Takashima, A, Koeda, K, Hara, H, Nakayama, N, Hironaka, S, Nishikawa, K, Kimura, Y, Amagai, K, et al
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2021;(2):467-476
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BACKGROUND This study evaluated the association between early tumor response at 8 weeks, previously reported as a positive outcome prognosticator, and health-related quality of life (HRQOL) in advanced gastric cancer (AGC) patients enrolled in the ABSOLUTE trial. METHODS HRQOL was assessed using the EuroQol-5 Dimension (EQ-5D) utility index score in patients with complete response (CR) + partial response (PR) and progressive disease (PD) at 8 weeks, and time-to-deterioration (TtD) of the EQ-5D score, with the preset minimally important difference (MID) of 0.05, was compared between these populations. Among the enrolled patients, 143 and 160 patients were assessable in weekly solvent-based paclitaxel (Sb-PTX) arm and weekly nanoparticle albumin-bound paclitaxel (nab-PTX) arm, respectively. RESULTS Changes of the EQ-5D score from baseline to 8 weeks in the nab-PTX arm were 0.0009 and - 0.1229 in CR + PR and PD patients, respectively; the corresponding values for the Sb-PTX arm were - 0.0019 and - 0.1549. For both treatments, changes of the EQ-5D score from baseline at 8 weeks were significantly larger in patients with PD than in those with CR + PR. The median TtD was 3.9 and 2.2 months in patients with CR + PR and PD, respectively, for nab-PTX [hazard ratio (HR) = 0.595, 95% confidence interval (CI) 0.358-0.989]. For Sb-PTX, the corresponding values were 4.7 and 2.0 months (HR = 0.494, 95% CI 0.291-0.841). CONCLUSIONS Early tumor shrinkage was associated with maintained HRQOL in AGC patients on the second-line chemotherapy with taxanes.
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Prospective Multicentered Safety and Feasibility Pilot for Endobronchial Intratumoral Chemotherapy.
Yarmus, L, Mallow, C, Akulian, J, Lin, CT, Ettinger, D, Hales, R, Voong, KR, Lee, H, Feller-Kopman, D, Semaan, R, et al
Chest. 2019;(3):562-570
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BACKGROUND Malignant airway obstruction (MAO) occurs in 30% of patients with advanced-stage lung cancer, leading to debilitating dyspnea, cough, and hemoptysis. Other than recanalization of the airways, these patients lack long-lasting palliative therapy. The goal of this study was to determine the safety and feasibility of local injection of paclitaxel into the airway wall with a novel microinjection catheter. METHODS In this multicentered prospective trial, 23 patients with non-small cell lung cancer and MAO were enrolled from July 2014 through June 2016 to undergo rigid bronchoscopy with recanalization, followed by injection of 1.5 mg of paclitaxel with a novel injection catheter. Primary end points consisted of safety (adverse events, severe adverse events, and unanticipated adverse device effects) as well as feasibility (number of injections, injection success). Secondary end points consisted of airway patency improvement, quality of life metrics, and need for further interventions and/or stenting. RESULTS Nineteen patients underwent rigid bronchoscopy with successful recanalization and paclitaxel injection. There were no adverse events, severe adverse events, or unanticipated adverse device effects. There was an average of 3.4 injections given for a total dose of 1.5 mg of paclitaxel in all patients. There was significantly less stenosis postprocedure vs preprocedure (25%-50% vs 75%-90%; P < .001), which was unchanged at 6 weeks (25%-50%). None of the participants required further interventions or airway stenting. CONCLUSIONS The injection of paclitaxel after recanalization of MAO in patients with non-small cell lung cancer is safe and feasible, using a novel airway injection device. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT02066103; URL: www.clinicaltrials.gov.
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A multi-national, randomised, open-label, parallel, phase III non-inferiority study comparing NK105 and paclitaxel in metastatic or recurrent breast cancer patients.
Fujiwara, Y, Mukai, H, Saeki, T, Ro, J, Lin, YC, Nagai, SE, Lee, KS, Watanabe, J, Ohtani, S, Kim, SB, et al
British journal of cancer. 2019;(5):475-480
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BACKGROUND NK105 is a novel nanoparticle drug delivery formulation that encapsulates paclitaxel (PTX) in polymeric micelles. We conducted an open-label phase III non-inferiority trial to compare the efficacy and safety of NK105 and PTX in metastatic or recurrent breast cancer. METHODS Patients were randomly assigned in a 1:1 ratio to receive either NK105 (65 mg/m2) or PTX (80 mg/m2) on days 1, 8 and 15 of a 28-day cycle. The primary endpoint was progression-free survival (PFS), with a non-inferiority margin of 1.215. RESULTS A total of 436 patients were randomised and 211 patients in each group were included in the efficacy analysis. The median PFS was 8.4 and 8.5 months for NK105 and PTX, respectively (adjusted hazard ratio: 1.255; 95% confidence interval: 0.989-1.592). The median overall survival and overall response rates were 31.2 vs. 36.2 months and 31.6% vs. 39.0%, respectively. The two groups exhibited similar safety profiles. The incidence of peripheral sensory neuropathy (PSN) was 1.4% vs. 7.5% (≥Grade 3) for NK105 and PTX, respectively. The patient-reported outcomes of PSN were significantly favourable for NK105 (P < 0.0001). CONCLUSIONS The primary endpoint was not met, but NK105 had a better PSN toxicity profile than PTX. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov: NCT01644890.
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Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial.
Paz-Ares, L, Dvorkin, M, Chen, Y, Reinmuth, N, Hotta, K, Trukhin, D, Statsenko, G, Hochmair, MJ, Özgüroğlu, M, Ji, JH, et al
Lancet (London, England). 2019;(10212):1929-1939
Abstract
BACKGROUND Most patients with small-cell lung cancer (SCLC) have extensive-stage disease at presentation, and prognosis remains poor. Recently, immunotherapy has demonstrated clinical activity in extensive-stage SCLC (ES-SCLC). The CASPIAN trial assessed durvalumab, with or without tremelimumab, in combination with etoposide plus either cisplatin or carboplatin (platinum-etoposide) in treatment-naive patients with ES-SCLC. METHODS This randomised, open-label, phase 3 trial was done at 209 sites across 23 countries. Eligible patients were adults with untreated ES-SCLC, with WHO performance status 0 or 1 and measurable disease as per Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were randomly assigned (in a 1:1:1 ratio) to durvalumab plus platinum-etoposide; durvalumab plus tremelimumab plus platinum-etoposide; or platinum-etoposide alone. All drugs were administered intravenously. Platinum-etoposide consisted of etoposide 80-100 mg/m2 on days 1-3 of each cycle with investigator's choice of either carboplatin area under the curve 5-6 mg/mL per min or cisplatin 75-80 mg/m2 (administered on day 1 of each cycle). Patients received up to four cycles of platinum-etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks in the immunotherapy groups and up to six cycles of platinum-etoposide every 3 weeks plus prophylactic cranial irradiation (investigator's discretion) in the platinum-etoposide group. The primary endpoint was overall survival in the intention-to-treat population. We report results for the durvalumab plus platinum-etoposide group versus the platinum-etoposide group from a planned interim analysis. Safety was assessed in all patients who received at least one dose of their assigned study treatment. This study is registered at ClinicalTrials.gov, NCT03043872, and is ongoing. FINDINGS Patients were enrolled between March 27, 2017, and May 29, 2018. 268 patients were allocated to the durvalumab plus platinum-etoposide group and 269 to the platinum-etoposide group. Durvalumab plus platinum-etoposide was associated with a significant improvement in overall survival, with a hazard ratio of 0·73 (95% CI 0·59-0·91; p=0·0047]); median overall survival was 13·0 months (95% CI 11·5-14·8) in the durvalumab plus platinum-etoposide group versus 10·3 months (9·3-11·2) in the platinum-etoposide group, with 34% (26·9-41·0) versus 25% (18·4-31·6) of patients alive at 18 months. Any-cause adverse events of grade 3 or 4 occurred in 163 (62%) of 265 treated patients in the durvalumab plus platinum-etoposide group and 166 (62%) of 266 in the platinum-etoposide group; adverse events leading to death occurred in 13 (5%) and 15 (6%) patients. INTERPRETATION First-line durvalumab plus platinum-etoposide significantly improved overall survival in patients with ES-SCLC versus a clinically relevant control group. Safety findings were consistent with the known safety profiles of all drugs received. FUNDING AstraZeneca.