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BACKGROUND AND OBJECTIVE: Paclitaxel and doxorubicin are associated with neurotoxicity and cardiotoxicity respectively. This study aimed at investigating the role of alpha-lipoic acid (ALA) in counteracting paclitaxel-induced neuropathy and doxorubicin-associated cardiotoxicity in women with breast cancer. PATIENTS AND METHODS: This randomized double-blind placebo-controlled prospective study included 64 patients with breast cancer who were randomized into control group (n = 32) which received 4 cycles of doxorubicin plus cyclophosphamide (every 21 days) followed by weekly doses of paclitaxel for 12 weeks plus placebo tablets once daily and ALA group (n = 32) which received the same chemotherapeutic regimen plus ALA 600 once daily for 6 months. Patients were assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4.0) for grading of neuropathy and by 12-item neurotoxicity questionnaire (Ntx-12). The assessment included also echocardiography and evaluation of serum levels of brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), and neurotensin (NT). Data were analyzed by paired and unpaired t-test, Mann-Whitney U test, and chi-square test. RESULTS: As compared to placebo, ALA provoked significant improvement in NCI-CTCAE neuropathy grading and Ntx-12 score after the end of 9th and 12th weeks of paclitaxel intake (p = 0.039, p = 0.039, p = 0.03, p = 0.004, respectively). At the end of the chemotherapy cycles, ALA resulted in significant decline in serum levels of BNP, TNF-α, MDA, and neurotensin (p < 0.05) as compared to baseline data and placebo. CONCLUSION: Alpha-lipoic acid may represent a promising adjuvant therapy to attenuate paclitaxel-associated neuropathy and doxorubicin-induced cardiotoxicity in women with breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03908528.
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Neoplasias de la Mama , Síndromes de Neurotoxicidad , Enfermedades del Sistema Nervioso Periférico , Ácido Tióctico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Cardiotoxicidad/etiología , Cardiotoxicidad/prevención & control , Doxorrubicina , Femenino , Humanos , Neurotensina/sangre , Síndromes de Neurotoxicidad/etiología , Paclitaxel , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Estudios Prospectivos , Ácido Tióctico/uso terapéutico , Factor de Necrosis Tumoral alfa/sangreRESUMEN
BLZ-100 (tozuleristide) is an intraoperative fluorescent imaging agent that selectively detects malignant tissue and can be used in real time to guide tumor resection. The purpose of this study was to assess the safety, tolerability, and pharmacokinetics of BLZ-100 and to explore the pharmacodynamics of fluorescence imaging of skin tumors. In this first-in-human study, BLZ-100 was administered intravenously to 21 adult patients 2 days before excising known or suspected skin cancers. Doses were 1, 3, 6, 12, and 18 mg, with 3-6 patients/cohort. Fluorescence imaging was conducted before and up to 48 h after dosing. BLZ-100 was well tolerated. There were no serious adverse events, deaths, or discontinuations due to adverse events, and no maximum tolerated dose (MTD) was identified. Headache (n = 2) and nausea (n = 2) were the only BLZ-100 treatment-related adverse events reported for >1 patient. Median time to maximal serum concentration was <0.5 h. Exposure based on maximal serum concentrations increased in a greater than dose-proportional manner. For intermediate dose-levels (3-12 mg), 4 of 5 basal cell carcinomas and 4 of 4 melanomas were considered positive for BLZ-100 fluorescence. BLZ-100 was well tolerated at all dose levels tested and these results support further clinical testing of this imaging agent in surgical oncology settings. Clinicaltrials.gov: NCT02097875.
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PURPOSE: Taxane-induced peripheral neuropathy (TIPN) is a common and bothersome toxicity. This study aimed to determine the incidence and severity of TIPN in patients with breast cancer and to investigate the relationship between TIPN and quality of life. METHODS: A total of 82 breast cancer patients with TIPN symptoms were included in this study. The criteria of National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.03) and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) were used to evaluate grading of sensory neuropathy and quality of life, respectively. Analysis of the data was done by IBM SPSS statistics version 23. RESULTS: A total of 346 patients received taxane-based chemotherapy and 82 patients (23.7%) experience TIPN. The mean (SD) global health status/quality of life, physical functioning, role functioning, and pain subscales were 60.63 (5.26), 80.64 (9.05), 81.77 (10.41), and 43.88 (11.27), respectively. There were significant negative correlations between global health status/quality of life, physical functioning, and role functioning subscales with the grade of neuropathy (r = -0.33, -0.80, and -0.61, respectively) and positive correlation between pain subscale and the grade of neuropathy (r = 0.70). CONCLUSION: This study shows a clear association between TIPN and worsened quality of life. These findings emphasize on detecting and management of TIPN in an effort to improve the quality of life of breast cancer patients.
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Neoplasias de la Mama/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Taxoides/efectos adversos , Adulto , Anciano , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Calidad de Vida , Encuestas y Cuestionarios , Taxoides/administración & dosificaciónRESUMEN
OBJECTIVE: Two-session Gamma Knife surgery (GKS) has recently been demonstrated to be an effective and less-invasive alternative for large brain metastases not treatable by microsurgical resection. This raises the clinical question of whether the 2-session GKS strategy further improves treatment outcomes for patients with symptomatic midsize brain metastases (2-10 cm3) as compared to single-session GKS. The present study aimed to compare the local therapeutic effects and toxicities of single-session and 2-session GKS for treating these lesions. METHODS: Patients with focal neurological deficits attributable to midsize brain metastases who underwent upfront GKS during the period from 2010 to 2018 were retrospectively identified from an institutional database. Patients for whom both post-GKS imaging studies and neurological evaluations from outpatient visits were available were eligible. Using propensity score-matching (PSM) analysis, unique matched pairs which had a similar likelihood of receiving 2-session GKS were generated. The main outcome measure was a composite of imaging and/or neurological worsening of the lesion of interest. Functional improvement and overall survival (OS) were also compared between the 2 treatment arms. RESULTS: In total, 219 cancer patients with 252 symptomatic midsize brain metastases were eligible. Of these 252 tumors, 176 and 76 were treated with single- and 2-session GKS, respectively. After PSM, 68 pairs of tumors were obtained. The Gray test showed that 2-session GKS achieved a longer local progression-free interval than single-session GKS (1-year local control rate: 84% vs 53%; HR 0.31, 95% CI 0.16-0.63, p = 0.001). Two-session GKS was also associated with greater functional improvement in KPS scores (mean 18.3 ± 14.6 vs 12.8 ± 14.1, p = 0.040). The median OS did not differ significantly between single- and 2-session GKS (15.6 vs 24.7 months; HR 0.69, 95% CI 0.44-1.10, p = 0.11). CONCLUSIONS: Two-session GKS achieved more durable local tumor control and greater functional improvement than single-session GKS for patients with symptomatic midsize brain metastases, although there was no OS advantage.
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Non-small cell lung cancer is a fatal disease associated with high morbidity. It is important to evaluate the effects of treatment on patient's quality of life. Quality of life can be assessed by using EORTC QLQ - C30 and EORTC QLQ - LC 13. Eighty-six patients were enrolled in the study. The patients were divided into four arms as follows: Patients in arm 1 received cisplatin 80 mg/m 2 and gemcitabine 1.25 g/m 2 as infusion separately in isotonic normal saline. Arm 2 received carboplatin 300 mg/m 2 and gemcitabine 1.2 mg/m 2 as infusion separately in 5% dextrose injection. Arm 3 received paclitaxel 100 mg/m 2 as infusion in isotonic normal saline and carboplatin 300 mg/m 2 as infusion in 5% dextrose injection. Arm 4 received pemetrexed 500 mg/m 2 as infusion in isotonic normal saline and carboplatin 300 mg/m 2 as infusion in 5% dextrose injection. The quality of life of the enrolled patients is based on EORTC QLQ - C30 and EORTC QLQ - LC 13 questionnaire. Prevalence of non-small cell lung cancer is more in males, 60-70 years of age. Most of the subjects were from rural areas and had only school-level education. The prevalence of non-small cell lung cancer was more with smokers, ex-smokers and patients with multiple social habits. Comorbidities also increase the risk of non-small cell lung cancer. By analyzing EORTC QLQ - C30 and EORTC QLQ - LC 13 questionnaires, it was found that diarrhea was found to be significant between the groups. Global health status and quality of life are distributed equally among each group. Quality of life and global health status are distributed equally among each sub groups.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Calidad de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Cisplatino/administración & dosificación , Estudios de Cohortes , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Humanos , Masculino , Paclitaxel/administración & dosificación , Pemetrexed/administración & dosificación , Estudios Prospectivos , Encuestas y Cuestionarios , GemcitabinaRESUMEN
PURPOSE: To better understand how quantitative sensory testing could help the clinician in the management of oxaliplatin-induced peripheral neuropathy in terms of earlier and more reliable detection, we conducted a two-year prospective study. METHODS: Thermal sensory assessment, tactile sensory assessment, neuropathic pain assessment and adverse events gradation (NCI-CTC) were performed during treatment and 6 months after treatment completion. RESULTS: 35 patients were enrolled and followed-up during one year. Cold and Warm Detection Thresholds were higher 6 months after treatment completion than at enrollment. Mechanical detection thresholds didn't change significantly. Neurotoxicity was mostly grade-1, only 18% grade-2 and no grade-3. Grade-2 patients received lower oxaliplatin cumulative dose than grade-1, which reveals effective dose adaptation and grade-2 patients were more likely to develop painful neuropathy. CONCLUSION: Thermal thresholds impairment emerges too late to help the clinician in the prophylaxis of neuropathy. Management of OXA-treatment based on NCI-CTC, as currently recommended, remains the best way to detect neuropathy and ensure treatment adaptation.
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Antineoplásicos/efectos adversos , Síndromes de Neurotoxicidad/terapia , Oxaliplatino/efectos adversos , Sensación Térmica/fisiología , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuralgia/inducido químicamente , Síndromes de Neurotoxicidad/etiología , Dimensión del Dolor , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Estudios Prospectivos , Percepción del Tacto/fisiología , Resultado del TratamientoRESUMEN
The goal of this study was to assess the antitumor efficacy and safety of lobaplatin-based regimens as the second line of treatment in patients with metastatic breast cancer (MBC) resistant to anthracyclines and taxanes, compared with that of cisplatin-based regimens. During August 2012 to April 2015, 87 patients who received lobaplatin-based regimens or cisplatin-based regimens were included. Medical records of the patients noted that lobaplatin (30â¯mg/m2) or cisplatin (25â¯mg/m2), combined with another chemotherapeutic agent such as Gemcitabine (1000â¯mg/m2) or Vinorelbine (25â¯mg/m2), was intravenously given to the patients on a basis of twenty-one days as one treatment cycle. All the patients were followed until August 2017. The endpoint of this study was progression-free survival (PFS), overall survival (OS), and estimated objective response rate (RR). Safety and drug tolerability data were also obtained. Lobaplatin-based regimens prolonged PFS compared to cisplatin-based regimens (median 13.2 vs 4.7â¯months, hazard ratioâ¯=â¯0.37, 95% confidence intervals: 0.21-0.67, Pâ¯=â¯.0007), while OS was not significantly different between the two groups (hazard ratioâ¯=â¯0.72, 95% confidence intervals: 0.40-1.30, Pâ¯=â¯.2767), as was objective RR (37.8% vs 33.4%, x2 = 0.19, Pâ¯=â¯.6653). Nausea/vomiting and renal injury were more frequent with cisplatin-based regimens. Our results show that lobaplatin-based regimens are superior to cisplatin in terms of efficacy and are better tolerated.
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BACKGROUND: The post-operative morbidity and mortality after CRS-HIPEC has been widely evaluated. However, there is a major discrepancy between rates reported due to different metrics and time of analysis used. OBJECTIVE: To evaluate the legitimacy of 90-day morbidity and mortality based on the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0 classification as criteria of quality for cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS: A prospective database of all patients undergoing CRS-HIPEC for peritoneal carcinomatosis between 2004 and 2015 was queried for 90-day morbidity and mortality and survival. RESULTS: Among 881 patients, the 90-day major complication rate based on NCI-CTCAE classification and Clavien-Dindo's classification were 51% (n = 447 patients) and 25% (n = 222 patients), respectively. Among patients who presented with a 90-day complication based on the NCI-CTCAE classification, 50% (n = 225 patients) presented a medical complication not reported by Clavien-Dindo's classification. After surgery, 24 patients (2.7%) died of post-operative complications, for only 10 (42%) of them the death occurred within 30-day after surgery. Occurrence of major complication based on either NCI-CTCAE classification, Clavien-Dindo's classification or the medical complication not reported by Clavien-Dindo's classification all negatively impacts the overall survival. CONCLUSION: Among commonly reported morbidity's classification, 90-day morbidity based on NCI-CTCAE classification represents a legitimate metric of CRS-HIPEC quality. Post-operative morbidity after CRS-HIPEC should be reported using 90-day NCI-CTCAE classification.
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Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Hipertermia Inducida/efectos adversos , Morbilidad/tendencias , Adolescente , Adulto , Rutas de Resultados Adversos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , National Cancer Institute (U.S.) , Complicaciones Posoperatorias/mortalidad , Estudios Prospectivos , Análisis de Supervivencia , Factores de Tiempo , Estados Unidos , Adulto JovenRESUMEN
INTRODUCTION: The combination of a fluoropyrimidine [5-fluorouracil (5-FU), capecitabine, or S-1] with a platinum analog (cisplatin or oxaliplatin) is the most widely accepted first-line chemotherapy regimen for metastatic or recurrent advanced gastric cancer (AGC), based on the results of clinical trials. However, there is little evidence to guide chemotherapy for elderly patients with AGC because of under-representation of this age group in clinical trials. Thus, the aim of this study is to determine the optimal chemotherapy regimen for elderly patients with AGC by comparing the efficacies and safeties of combination therapy versus monotherapy as first-line chemotherapy. METHODS: This study is a randomized, controlled, multicenter, phase III trial. A total of 246 elderly patients (≥70 years old) with metastatic or recurrent AGC who have not received previous palliative chemotherapy will be randomly allocated to a combination therapy group or a monotherapy group. Patients randomized to the combination therapy group will receive fluoropyrimidine plus platinum combination chemotherapy (capecitabine/cisplatin, S-1/cisplatin, capecitabine/oxaliplatin, or 5-FU/oxaliplatin), and those randomized to the monotherapy group will receive fluoropyrimidine monotherapy (capecitabine, S-1, or 5-FU). The primary outcome is the overall survival of patients in each treatment group. The secondary outcomes include progression-free survival, response rate, quality of life, and safety. DISCUSSION: We are conducting this pragmatic trial to determine whether elderly patients with AGC will obtain the same benefit from chemotherapy as younger patients. We expect that this study will help guide decision-making for the optimal treatment of elderly patients with AGC.
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PURPOSE: Oxaliplatin neurotoxicity has a spectrum of manifestations from an often reversible acute neurotoxicity to a more irreversible "stocking and glove" chronic neuropathy that is associated with high morbidity. Quantitative sensory testing (QST) is a noninvasive psychometric testing method that can potentially be used in the clinic setting to measure subclinical neurologic changes early on to identify patients that will experience chronic oxaliplatin-induced peripheral neuropathy at 1 year. PATIENTS AND METHODS: Thirty patients with gastrointestinal malignancies who were receiving oxaliplatin were recruited. QST and patient-reported outcomes were assessed at baseline; during infusion cycles 1, 2, 4, and 6; and at 1 year. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0, chronic neuropathy scores were assessed at the 1-year time point. The variables at each time point were evaluated for prediction of 1-year chronic neuropathy scores. RESULTS: We found that patients with preexisting subclinical neuropathy were more likely to experience grades 2 and 3 chronic neuropathy than were those who did not have this condition (heat detection threshold, Spearman correlation coefficient (rs) = 0.39; P = .037; pellet retrieval time, rs = 0.47; P = .024). Patients in whom thermal and cutaneous sensory deficits developed with cycle 1 infusion were also more likely to experience grades 2 and 3 neuropathy at 1 year (cold detection threshold, rs = 0.50; P = .007; heat detection threshold, rs = 0.39; P = .042; cutaneous detection threshold, rs = 0.42; P = .043). CONCLUSION: QST provides a noninvasive, commercially available, and feasible clinical test to select patients, even before oxaliplatin treatment, who are likely to experience moderate to severe chronic peripheral neuropathy.
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Antineoplásicos/efectos adversos , Neoplasias del Sistema Digestivo/tratamiento farmacológico , Hipoestesia/diagnóstico , Síndromes de Neurotoxicidad/diagnóstico , Compuestos Organoplatinos/efectos adversos , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Adulto , Anciano , Enfermedades Asintomáticas , Enfermedad Crónica , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Femenino , Humanos , Hipoestesia/inducido químicamente , Hipoestesia/fisiopatología , Masculino , Persona de Mediana Edad , Destreza Motora , Examen Neurológico , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/fisiopatología , Oxaliplatino , Neoplasias Pancreáticas/tratamiento farmacológico , Evaluación del Resultado de la Atención al Paciente , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Propiocepción , Estudios Prospectivos , Neoplasias del Recto/tratamiento farmacológico , Umbral Sensorial , Trastornos Somatosensoriales/inducido químicamente , Trastornos Somatosensoriales/diagnóstico , Trastornos Somatosensoriales/fisiopatología , Tacto , VibraciónRESUMEN
OBJECT: Spinal chordomas can have high local recurrence rates after surgery with or without conventional dose radiation therapy (RT). Treatment outcomes and prognostic factors after high-dose proton-based RT with or without surgery were assessed. METHODS: The authors conducted a retrospective review of 126 treated patients (127 lesions) categorized according to disease status (primary vs recurrent), resection (en bloc vs intralesional), margin status, and RT timing. RESULTS: Seventy-one sacrococcygeal, 40 lumbar, and 16 thoracic chordomas were analyzed. Mean RT dose was 72.4 GyRBE (relative biological effectiveness). With median follow-up of 41 months, the 5-year overall survival (OS), local control (LC), locoregional control (LRC), and distant control (DC) for the entire cohort were 81%, 62%, 60%, and 77%, respectively. LC for primary chordoma was 68% versus 49% for recurrent lesions (p = 0.058). LC if treated with a component of preoperative RT was 72% versus 54% without this treatment (p = 0.113). Among primary tumors, LC and LRC were higher with preoperative RT, 85% (p = 0.019) and 79% (0.034), respectively, versus 56% and 56% if no preoperative RT was provided. Overall LC was significantly improved with en bloc versus intralesional resection (72% vs 55%, p = 0.016), as was LRC (70% vs 53%, p = 0.035). A trend was noted toward improved LC and LRC for R0/R1 margins and the absence of intralesional procedures. CONCLUSIONS: High-dose proton-based RT in the management of spinal chordomas can be effective treatment. In patients undergoing surgery, those with primary chordomas undergoing preoperative RT, en bloc resection, and postoperative RT boost have the highest rate of local tumor control; among 28 patients with primary chordomas who underwent preoperative RT and en bloc resection, no local recurrences were seen. Intralesional and incomplete resections are associated with higher local failure rates and are to be avoided.
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Cordoma/radioterapia , Vértebras Lumbares , Neoplasias de la Columna Vertebral/radioterapia , Vértebras Torácicas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Cordoma/patología , Cordoma/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioterapia Adyuvante , Estudios Retrospectivos , Neoplasias de la Columna Vertebral/patología , Neoplasias de la Columna Vertebral/cirugía , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: This randomized, open-label phase II study compared the efficacy of sunitinib monotherapy with that of single-agent standard-of-care (SOC) chemotherapy in patients with previously treated advanced triple-negative breast cancer (TNBC). METHODS: Patients with advanced TNBC, relapsed after anthracycline- and taxane-based chemotherapy, were randomized to receive either sunitinib (37.5 mg/day) or the investigator's choice of SOC therapy. Progression-free survival was the primary endpoint. RESULTS: Median progression-free survival was 2.0 months with sunitinib and 2.7 months with SOC chemotherapy (one-sided P = 0.888). Median overall survival was not prolonged with sunitinib (9.4 months) compared with SOC chemotherapy (10.5 months; one-sided P = 0.839). The objective response rate was 3% with sunitinib and 7% with SOC chemotherapy (one-sided P = 0.962). CONCLUSIONS: Sunitinib monotherapy did not improve efficacy compared with SOC chemotherapy in patients with previously treated advanced TNBC, for which identification of effective treatments and therapeutic targets remains an urgent need. TRIAL REGISTRATION: NCT00246571.