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1.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167209, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38701955

RESUMEN

FOLFOX is a combination of chemotherapeutic agents (5-fluorouracil, leucovorin, and oxaliplatin) and is used to treat advanced colorectal cancer (CRC) but induces various side effects. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most critical side effects that compromise the quality of life of patients with CRC undergoing FOLFOX chemotherapy. This study aimed to evaluate circulating miRNA, cortisol and catecholamine as potential biomarkers that can predict FOLFOX-CIPN symptoms. High-throughput microRNA (miRNA) sequencing was performed on the RNA circulating in the plasma of eight patients with CRC who underwent FOLFOX chemotherapy. miRNA expression profiles were evaluated according to two groups: those who underwent ≤3 cycles and those who underwent ≥6 cycles of FOLFOX chemotherapy. The identified miRNAs were validated in 27 patients with CRC who underwent FOLFOX chemotherapy using quantitative reverse transcription polymerase chain reaction. Target genes were predicted using bioinformatics and functional analyses. Cortisol and catecholamine concentrations in peripheral plasma were measured using an enzyme-linked immunosorbent assay. miR-3184-5p was differentially expressed when miRNA expression was compared between the groups that underwent ≤3 and ≥6 cycles of FOLFOX chemotherapy. Cortisol levels were significantly higher in the group that underwent ≥6 cycles of FOLFOX chemotherapy than in the group that underwent ≤3 cycles. This study suggests that miR-3184-5p may be a potential marker for predicting CIPN.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorrectales , Fluorouracilo , Leucovorina , MicroARNs , Compuestos Organoplatinos , Enfermedades del Sistema Nervioso Periférico , Humanos , Leucovorina/uso terapéutico , Leucovorina/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/genética , Enfermedades del Sistema Nervioso Periférico/sangre , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/sangre , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Persona de Mediana Edad , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/uso terapéutico , MicroARNs/sangre , MicroARNs/genética , Anciano , Hidrocortisona/sangre , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Adulto , Catecolaminas/sangre
2.
Medicine (Baltimore) ; 102(50): e36690, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38115255

RESUMEN

RATIONALE: Although rare, systemic hypersensitivity reactions to nedaplatin chemotherapy arise rapidly and can be life-threatening. The causes are unclear, and multiple potential mechanisms exist. Here, we report a case of systemic hypersensitivity reaction to nedaplatin and review the literature to establish a recommended protocol. PATIENT CONCERNS: A 62-year-old man was being treated for squamous lung cancer with multiple metastases. On the first day of chemotherapy, 5 minutes after nedaplatin infusion, he developed panic, shortness of breath, and dyspnea with rapid heart rate, reduced oxygen saturation, and elevated blood pressure. DIAGNOSES: The symptoms indicated that the patient had developed a severe hypersensitivity reaction to nedaplatin, which could be life-threatening without immediate intervention. INTERVENTION: Nedaplatin was discontinued, and he was treated with oxygen, ECG monitoring, finger pulse oximeter monitoring, 10 mg dexamethasone sodium phosphate injected intravenously, 20 mg diphenhydramine hydrochloride injected intramuscularly, and 40 mg methylprednisolone sodium succinate injected intravenously. OUTCOME: His allergic symptoms resolved, and once his vital signs stabilized, he was given 5 mg oral desloratadine once daily and 10 mg oral ebastine once daily to alleviate the effects of the allergic reaction. Once his vital signs remained stable without any special supportive treatment, he was discharged from the hospital. His chemotherapy regimen was discontinued, with no plan for a follow-up treatment due to the possibility of cross-allergic reactions between platinum-based drugs. LESSONS: Clinical use of nedaplatin should be monitored and managed intensively for prevention and treatment of hypersensitivity reactions. Care should be taken to control the titration rate during infusion while closely monitoring vital signs. Clinical staff should be prepared to treat allergic symptoms as soon as they appear. The acute phase should involve immediate discontinuation of the drug; intravenous saline infusion for volume expansion; rapid assessment of circulation, airway, respiration, state of consciousness, and skin condition; and administration of oxygen, antihistamines, and epinephrine as appropriate for anaphylaxis. More randomized clinical trials are needed to elucidate appropriate preventative and management strategies to improve patient safety and support their successful completion of clinical treatment programs.


Asunto(s)
Anafilaxia , Antineoplásicos , Hipersensibilidad a las Drogas , Masculino , Humanos , Persona de Mediana Edad , Antineoplásicos/efectos adversos , Compuestos Organoplatinos/efectos adversos , Anafilaxia/tratamiento farmacológico , Oxígeno , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/tratamiento farmacológico
3.
Support Care Cancer ; 31(7): 386, 2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37294347

RESUMEN

PURPOSE: The purpose of this retrospective cohort study was to evaluate whether several potentially preventive therapies reduced the rate of oxaliplatin-induced peripheral neuropathy (OIPN) in colorectal cancer patients and to assess the relationship of sociodemographic/clinical factors with OIPN diagnosis. METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results database combined with Medicare claims. Eligible patients were diagnosed with colorectal cancer between 2007 and 2015, ≥ 66 years of age, and treated with oxaliplatin. Two definitions were used to denote diagnosis of OIPN based on diagnosis codes: OIPN 1 (specific definition, drug-induced polyneuropathy) and OIPN 2 (broader definition, additional codes for peripheral neuropathy). Cox regression was used to obtain hazard ratios (HR) with 95% confidence intervals (CI) for the relative rate of OIPN within 2 years of oxaliplatin initiation. RESULTS: There were 4792 subjects available for analysis. At 2 years, the unadjusted cumulative incidence of OIPN 1 was 13.1% and 27.1% for OIPN 2. For both outcomes, no therapies reduced the rate of OIPN diagnosis. The anticonvulsants gabapentin and oxcarbazepine/carbamazepine were associated with an increased rate of OIPN (both definitions) as were increasing cycles of oxaliplatin. Compared to younger patients, those 75-84 years of age experienced a 15% decreased rate of OIPN. For OIPN 2, prior peripheral neuropathy and moderate/severe liver disease were also associated with an increased hazard rate. For OIPN 1, state buy-in health insurance coverage was associated with a decreased hazard rate. CONCLUSION: Additional studies are needed to identify preventive therapeutics for OIPN in cancer patients treated with oxaliplatin.


Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Enfermedades del Sistema Nervioso Periférico , Estados Unidos , Humanos , Anciano , Oxaliplatino/efectos adversos , Antineoplásicos/efectos adversos , Estudios Retrospectivos , Compuestos Organoplatinos/efectos adversos , Medicare , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/epidemiología , Enfermedades del Sistema Nervioso Periférico/prevención & control , Neoplasias Colorrectales/tratamiento farmacológico
4.
Ann Allergy Asthma Immunol ; 131(4): 501-512.e9, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37321446

RESUMEN

BACKGROUND: Cytokine-release reactions (CRR) induced by platinum-based chemotherapy, manifesting with fever, chills, and rigors, are poorly understood and not easily prevented by usual premedication or desensitization. OBJECTIVE: To gain a better understanding of platinum-induced CRR and to explore the use of anakinra as a tool to prevent its clinical manifestations. METHODS: A cytokine and chemokine panel was obtained before and after platinum infusion in 3 cases with a mixed (immunoglobulin E-mediated and CRR) platinum-induced hypersensitivity reaction and in 5 controls either tolerant or with an immunoglobulin E-mediated platinum-induced hypersensitivity reaction. Anakinra was given as premedication in the 3 CRR cases. RESULTS: Cytokine-release reaction was associated with a marked release of interleukin (IL)-2, IL-5, IL-6, IL-10, and tumor necrosis factor-ɑ in all cases whereas only IL-2 and IL-10 increased in some controls after platinum infusion, and to a lesser extent than in cases. Anakinra seemed to block CRR symptoms in 2 cases. In the third case, who initially had CRR symptoms despite anakinra, tolerance to oxaliplatin appeared to develop after repeated re-exposures, as suggested by the decreasing levels of cytokines after oxaliplatin, except IL-10, and the capacity to progressively shorten the desensitization protocol and taper the premedication, in addition to the negativization of the oxaliplatin skin test result. CONCLUSION: In patients with platinum-induced CRR, anakinra could be a useful premedication to block its clinical manifestations, and monitoring of IL-2, IL-5, IL-6, IL-10, and tumor necrosis factor-ɑ could help predict tolerance development, thereby allowing safe adjustments to the desensitization protocol and premedication.


Asunto(s)
Antineoplásicos , Hipersensibilidad a las Drogas , Hipersensibilidad , Humanos , Oxaliplatino/efectos adversos , Antineoplásicos/efectos adversos , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Platino (Metal)/uso terapéutico , Interleucina-2/uso terapéutico , Interleucina-10 , Interleucina-6 , Factor de Necrosis Tumoral alfa , Interleucina-5 , Compuestos Organoplatinos/efectos adversos , Hipersensibilidad a las Drogas/tratamiento farmacológico , Citocinas , Hipersensibilidad/tratamiento farmacológico , Inmunoglobulina E
5.
Neurosci Lett ; 788: 136863, 2022 09 25.
Artículo en Inglés | MEDLINE | ID: mdl-36067900

RESUMEN

Transient receptor potential (TRP) channels are involved in the development of oxaliplatin-induced neuropathic pain, a frequent and debilitating side effect of cancer therapy. Here we explored whether oxaliplatin-induced changes in the expression of TRP channels, as well as the development of pain-related behaviours, differed between male and female animals. Adult rats were injected with oxaliplatin or saline and mechanical and cold allodynia were evaluated using Von Frey and Choi Tests. The mRNA levels of TRPV1, TRPM8 and TRPA1 were assessed in lumbar ganglia and spinal cord by using real time RT-PCR. Oxaliplatin administration induced mechanical and cold hypersensitivity and allodynia in both sexes, with more severe responses to cold stimulation detected in females. Oxaliplatin also induced a significant increase in the expression of TRPV1, TRPM8 and TRPA1 in lumbar dorsal root ganglia. Interestingly, while TRPV1 and TRPA1 upregulation showed no sex difference, the increase in TRPM8 mRNA levels was more pronounced in female ganglia, correlating with the increased sensitivity to innocuous cold stimuli observed in females. TRPV1 and TRPM8 were also found to be upregulated in the spinal cord of animals of both sexes. Our results reveal previously undescribed changes in the expression of TRP channels occurring in peripheral ganglia and spinal cord of both male and female oxaliplatin-treated animals, with some of these changes exhibiting sex-related differences that could underlie the development of sex-specific patterns of pain-related behaviours.


Asunto(s)
Neuralgia , Canales Catiónicos TRPM , Canales de Potencial de Receptor Transitorio , Animales , Frío , Síndromes Periódicos Asociados a Criopirina , Femenino , Ganglios Espinales/metabolismo , Hiperalgesia/inducido químicamente , Hiperalgesia/metabolismo , Masculino , Neuralgia/metabolismo , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/metabolismo , Oxaliplatino/efectos adversos , ARN Mensajero/metabolismo , Ratas , Canal Catiónico TRPA1/metabolismo , Canales Catiónicos TRPM/metabolismo , Canales de Potencial de Receptor Transitorio/metabolismo
6.
In Vivo ; 36(5): 2447-2452, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36099124

RESUMEN

BACKGROUND/AIM: Advanced gastric cancer (AGC) rarely presents with disseminated intravascular coagulation (DIC) at the time of diagnosis. Chemotherapy should be selected in consideration of hematological toxicities because these patients are at high risk of hemorrhagic complications. The leucovorin, fluorouracil, and oxaliplatin (FOLFOX) regimen is an effective and less toxic regimen for patients with AGC and poor performance status. PATIENTS AND METHODS: The present study assessed overall survival of all patients receiving first-line chemotherapy with and without DIC using Kaplan-Meier methods and examined the clinicopathological factors, DIC parameters, response, and survival of five patients with AGC and DIC who received FOLFOX in the first-line setting between February 2017 and February 2020. RESULTS: Among the patients, four patients (80%) recovered from DIC after a median of 12 days of FOLFOX therapy (range=12-25), and their platelet count gradually increased within 1 week after the start of chemotherapy. The median progression-free survival and overall survival were 46 (range=22-296) and 115 days (range=83-324), respectively. No patients experienced adverse events necessitating treatment discontinuation, including gastrointestinal bleeding and thrombocytopenia. Moreover, all patients received second-line treatment after progression, and one patient exhibited improvement of DIC symptoms following nab-paclitaxel and ramucirumab treatment. CONCLUSION: FOLFOX therapy is well tolerated and effective in patients with AGC initially presenting with DIC and subsequent second-line treatment might be crucial for better prognosis.


Asunto(s)
Coagulación Intravascular Diseminada , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Coagulación Intravascular Diseminada/diagnóstico , Coagulación Intravascular Diseminada/tratamiento farmacológico , Coagulación Intravascular Diseminada/etiología , Humanos , Compuestos Organoplatinos/efectos adversos , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/tratamiento farmacológico
7.
Pan Afr Med J ; 42: 141, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36160274

RESUMEN

Introduction: a capecitabine and oxaliplatin drug combination regimen has shown a survival benefit in patients with advanced colorectal cancer, yet its administration represents an attractive option for low resource settings. This study aimed to describe the therapeutic utility, efficacy and safety of a capecitabine plus oxaliplatin drug combination in patients with colorectal cancer. Methods: a review of medical records of sixty adult patients with histological diagnosis of colorectal cancer at Tygerberg Hospital between June 2012 and June 2017 was conducted. The overall response rate was assessed after a three cycle regime of capecitabine and oxaliplatin with the progression-free survival (PSF) results estimated using the Kaplan-Meier methods. Results: among the 60 participants identified over the study period, the median age was 53 years with 45% being female (n=27). Records showed that 58.33% of patients had the colon as the primary site and 68.33% of patients had synchronous liver metastases at presentation. On average, all patients received 6 cycle regimes of capecitabine and oxaliplatin. Sixty percent of the patients received this treatment regime with palliative intent while in the radical-intent group, equal numbers of patients received the regime as either neoadjuvant or adjuvant. A liver resection was also performed in 20 patients (31.8%). The overall response rate was 69.6% with 13 patients attaining a complete response. Disease progression was reported in 30.4% and the 1-year progression free survival was 44.5% (95% CI: 0.31-0.57) while the 2-year progression free survival was 25.1% (95% CI: 0.14-0.38). Regarding safety, thrombocytopenia was the most frequent adverse event (18.5%) and overall, 15.1% of patients experienced grade 3 and 4 toxicity. Conclusion: a drug combination of capecitabine and oxaliplatin showed a good overall response rate and survival particularly in patients with resectable colorectal liver metastases.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias Hepáticas , Neoplasias del Recto , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina/efectos adversos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Desoxicitidina/efectos adversos , Supervivencia sin Enfermedad , Combinación de Medicamentos , Femenino , Fluorouracilo/efectos adversos , Hospitales , Humanos , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Neoplasias del Recto/tratamiento farmacológico , Estudios Retrospectivos
8.
Eur J Cancer ; 174: 40-47, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35970035

RESUMEN

BACKGROUND: This phase 1b trial evaluated the toxicity and efficacy of S-1, irinotecan, and oxaliplatin combination therapy (S-IROX) as first-line chemotherapy in patients with advanced pancreatic cancer (APC). METHODS: Patients aged 20-75 years with APC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible to receive escalating doses of S-1 (60 or 80 mg m2·day) on days 1-7, fixed doses of oxaliplatin (85 mg/m2) biweekly, and escalating doses of irinotecan (150, 165, or 180 mg/m2) once every 2 weeks. In the dose-escalation cohort, a 3 + 3 design was used to determine the maximum-tolerated dose (MTD) and explore the recommended dose (RD). A dose-expansion cohort was added to further evaluate the safety and efficacy of the combination. This trial was registered at UMIN-CTR (UMIN000012054). RESULTS: Approximately 47 patients were enrolled, of whom 45 were eligible for the analysis. The MTD was not determined, but the RD was determined to be dose level 1 based on a review of data from each level. Among the 45 patients, the ORR was 51.1% [95% confidence interval (CI), 35.8-66.3%]. The median progression-free survival and median overall survival was 6.9 months (95% CI, 5.1-8.8 months) and 15.8 months (95% CI, 9.8-20.8 months), respectively. Common adverse events included neutropenia, elevated liver enzyme levels, diarrhoea, and nausea. CONCLUSIONS: The S-IROX regimen showed promising efficacy with manageable toxicities in Japanese patients with APC. A randomised phase 2/3 trial comparing S-IROX, mFOLFIRINOX, and gemcitabine plus nab-paclitaxel is currently ongoing (jRCTs031190009).


Asunto(s)
Camptotecina , Neoplasias Pancreáticas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/efectos adversos , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Fluorouracilo/efectos adversos , Humanos , Irinotecán/efectos adversos , Estudios Multicéntricos como Asunto , Compuestos Organoplatinos/efectos adversos , Oxaliplatino/efectos adversos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/etiología , Neoplasias Pancreáticas
9.
Clin Colorectal Cancer ; 21(4): 354-361, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35934636

RESUMEN

BACKGROUND: Additive chemotherapeutic treatment of UICC-stage -III / IV colon cancer with fluorouracil, leucovorin and oxaliplatin is widely accepted as current standard of treatment after R0-resection. However, as patients.. survival is increasing, long-term side effects of chemotherapeutic agents such as second cancer development are becoming increasingly important. PATIENTS: We therefore investigated a total of 2 856 Patients with UICC-stage III / IV colon cancer, 223 of whom (7.8%) had developed a subsequent second cancer. RESULTS: Median follow-up was 73.2 months (range 209.9 months, 95%-CI 69.8-76.9). Most frequent second cancers were prostate cancer (18.4%), colon cancer (16.1%), breast cancers (8.1%), lung cancer (8.1%), rectal cancer (4.9%) and uterine cancer (4.9%). However, in comparison to non-treated patients this did not represent a significantly increased risk for subsequent second cancer in patients after treatment with additive chemotherapy. Of interest, our data suggest a significantly decreased second cancer rate in patients treated with FOLFOX compared to FUFOL for additive treatment. CONCLUSIONS: Second cancer development was not increased after additive chemotherapy for colon cancer, which is a novel aspect in the ongoing discussions on reduction of adjuvant treatment to 3 months or treatment of lymph node negative patients. Novelty and Impact Statement To our knowledge, this is the first population-based study analyzing second cancer development after additive chemotherapy in patients with UICC III-IV colon cancer. The results have an important impact on the surveillance and long-term follow-up of cancer patients.


Asunto(s)
Neoplasias del Colon , Neoplasias Primarias Secundarias , Masculino , Humanos , Neoplasias Primarias Secundarias/tratamiento farmacológico , Quimioterapia Adyuvante/efectos adversos , Compuestos Organoplatinos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Leucovorina , Neoplasias del Colon/patología , Fluorouracilo/efectos adversos , Estadificación de Neoplasias
10.
Int J Clin Oncol ; 27(10): 1616-1623, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35867198

RESUMEN

PURPOSE: Temporary ileostomy is sometimes created after colorectal surgery and may cause renal impairment. However, the impact of ileostomy on renal function during adjuvant chemotherapy for colorectal cancer (CRC) remains unknown. The aim of the present study was to examine the effects of ileostomy on renal function during adjuvant chemotherapy. METHODS: We examined 184 patients who received adjuvant CAPOX therapy (capecitabine and oxaliplatin) for CRC with or without ileostomy between January 2011 and December 2020 at the University of Tokyo Hospital. Clinicopathological factors, including renal function, were retrospectively reviewed in association with temporary ileostomy. Factors associated with reductions in the estimated glomerular filtration rate (eGFR) during CAPOX therapy were analyzed. RESULTS: Eighteen patients (10%) underwent temporary ileostomy. The maximum decrease in eGFR during CAPOX therapy was significantly higher in patients with than in those without ileostomy (- 16.1 vs. - 5.6 mL/min/1.73m2, p = 0.003). A multivariate analysis identified ileostomy as one of factors independently associated with reductions in eGFR during CAPOX therapy (p = 0.003). The cumulative number of readmission due to dehydration was also higher in patients with ileostomy (33% vs. 1%, p < 0.001). CONCLUSIONS: Ileostomy significantly reduced eGFR during adjuvant CAPOX therapy. Therefore, renal function needs to be monitored during CAPOX therapy, particularly in patients with ileostomy.


Asunto(s)
Ileostomía , Compuestos Organoplatinos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina/efectos adversos , Quimioterapia Adyuvante/efectos adversos , Fluorouracilo , Humanos , Ileostomía/efectos adversos , Compuestos Organoplatinos/efectos adversos , Oxaliplatino/efectos adversos , Estudios Retrospectivos , Factores de Riesgo
11.
Recenti Prog Med ; 113(6): 19e-24e, 2022 06.
Artículo en Italiano | MEDLINE | ID: mdl-35758127

RESUMEN

Cetuximab in combination with chemotherapy is a standard first-line treatment regimen for patients with metastatic colorectal cancer (mCRC) RAS wild-type (wt); however, the efficacy of cetuximab plus leucovorin, fluorouracil and oxaliplatin (FOLFOX) had never been demonstrated in a prospective, randomized, controlled phase III study. The TAILOR study is the first randomized, multicenter, prospective Phase III study evaluating the addition of cetuximab to FOLFOX in a RAS wt Chinese population and thus providing confirmatory data for the efficacy and safety of cetuximab plus FOLFOX versus FOLFOX alone.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cetuximab/efectos adversos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Fluorouracilo/efectos adversos , Humanos , Leucovorina/efectos adversos , Metástasis de la Neoplasia/tratamiento farmacológico , Compuestos Organoplatinos/efectos adversos , Estudios Prospectivos , Neoplasias del Recto/inducido químicamente , Neoplasias del Recto/tratamiento farmacológico
12.
Ann Surg Oncol ; 29(8): 5084-5091, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35322307

RESUMEN

BACKGROUND: Peritoneal metastasis (PM) remains a major obstacle in the treatment of stage IV gastric cancer. This is a dose-escalation study of intraperitoneal (IP) paclitaxel combined with intravenous (IV) fluorouracil, leucovorin, and oxaliplatin (FOLFOX) to determine the recommended phase II dose in gastric cancer patients. METHODS: Patients with gastric adenocarcinoma and PM were enrolled. The recommended phase II dose of IP paclitaxel was determined using the standard "3 + 3" dose escalation with planned doses ranging from 40 to 100 mg/m2. IV FOLFOX was administered on the same day (oxaliplatin 100 mg/m2 (day 1), leucovorin 100 mg/m2 (day 1), fluorouracil 2,400 mg/m2 over 46 hours (day 1)). Both IP and IV regimens were repeated every 2 weeks. RESULTS: Among the 13 patients, there was no DLT at 40 and 60 mg/m2. Two patients had grade 3 febrile neutropenia at 80 mg/m2, and the recommended phase II dose was 60 mg/m2. Other patients underwent IP paclitaxel and FOLFOX without serious adverse events. Seven patients underwent second-look diagnostic laparoscopy, and the average change in PCI score was -7.0 ± 9.7. Conversion surgery rate was 23.1% (n = 3). The median overall survival was 16.6 months (95% confidence interval, 16.6-N/A), and progression-free survival was 9.6 months (95% confidence interval, 4.7-N/A). All adverse events were tolerable and manageable. CONCLUSIONS: The biweekly regimen of IP paclitaxel and FOLFOX is safe and the recommended dose of IP paclitaxel for a phase II trial is 60 mg/m2.


Asunto(s)
Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Paclitaxel , Neoplasias Peritoneales , Neoplasias Gástricas , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Administración Intravenosa , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Relación Dosis-Respuesta a Droga , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Humanos , Infusiones Parenterales , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Leucovorina/uso terapéutico , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/uso terapéutico , Oxaliplatino/administración & dosificación , Oxaliplatino/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/cirugía , Segunda Cirugía , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Análisis de Supervivencia , Resultado del Tratamiento
13.
Clin Colorectal Cancer ; 21(3): 220-228, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35304089

RESUMEN

BACKGROUND: Obesity is associated with an increased risk of development and recurrence of colorectal cancer. The role of obesity in metastatic colorectal cancer patients (pts) is still unclear, especially in those treated with triplet plus bevacizumab (bev). The aim of our study was to evaluate the prognostic and predictive role of BMI in metastatic colorectal cancer pts treated with FOLFOXIRI plus bev or FOLFIRI/FOLFOX plus bev in the TRIBE and TRIBE-2 trial. MATERIALS AND METHODS: A total of 1160 pts enrolled in TRIBE and TRIBE-2 trials were included. Baseline height and weight were used to assign pts to one of the following BMI categories: underweight (group A = BMI <18.5 kg/m2; 52 pts), normal (group B = BMI 18.5-29.9 kg/m2; 952 pts) and obese (group C > 30 kg/m2; 156 pts). RESULTS: In our population, no differences in terms of PFS (P = .43) or OS (P = .99) resulted between 3 groups. No interaction effect between treatment arm and BMI was evident in terms of PFS (Group A HR: 0.65 [95%CI: 0.36-1.16]; Group B HR: 0.77 [95%CI: 0.67-0.88]; Group C HR: 0.67 [95%CI: 0.48-0.93]; P for interaction = .75) or OS (Group A HR: 0.57 [95%CI: 0.29-1.12]; Group B HR: 0.85 [95%CI: 0.73-0.99];Group C HR: 0.69 [95%CI: 0.48-1.01] P for interaction = .36). No statistically significant difference in terms of dose reductions due to toxicities were found according to BMI in the overall population (P = .48) and in pts treated with FOLFOXIRI plus bev (P = .57). CONCLUSION: BMI was neither prognostic or predictive for PFS and OS in our population. Our analyses showed that the advantage of FOLFOXIRI plus bev versus FOLFIRI/FOLFOX plus bev was independent from BMI.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Índice de Masa Corporal , Camptotecina/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Colorrectales/patología , Fluorouracilo/efectos adversos , Humanos , Leucovorina/efectos adversos , Obesidad/complicaciones , Obesidad/epidemiología , Compuestos Organoplatinos/efectos adversos , Pronóstico , Neoplasias del Recto/tratamiento farmacológico , Resultado del Tratamiento
14.
J Oncol Pharm Pract ; 28(7): 1641-1644, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35119329

RESUMEN

INTRODUCTION: Oxaliplatin is a platinum containing alkylating agent commonly used in the management of colorectal cancers. The most common dose-limiting toxicity of oxaliplatin is peripheral neuropathy, which can be severe enough to cause treatment discontinuation. We present a case of dysarthria and laryngopharyngeal dysesthesia (LPD) that developed during the first dose of oxaliplatin, which showed dose-dependent reduction in severity in subsequent cycles. CASE REPORT: A 52-year-old female patient with adenocarcinoma of rectum (pT4N2M0) was prescribed oxaliplatin (130 mg/m2) and capecitabine(2000mg/m2). She developed heaviness in the tongue, slurred speech, jaw pain, perioral paresthesia within 30 min after the end of 3 h infusion of oxaliplatin in the first cycle. The symptoms subsided without any sequelae in two days. However, in the subsequent cycles as the dose of the oxaliplatin was reduced, similar symptoms reappeared but were of reduced in severity. No dysesthesia symptoms were observed in the 4th cycle when the oxaliplatin was administered at 85 mg/m2. MANAGEMENT AND OUTCOME: As and when the patient developed symptoms - slurred speech, jaw pain during the first three cycles, she was managed with inj. Hydrocortisone (100 mg i.v.) and one ampoule of pheniramine (45 mg i.v.). DISCUSSION: Occurrence of laryngopharyngeal dysesthesia due to oxaliplatin does not warrant drug withdrawal, dose titration can be helpful, thereby preventing the drug withdrawal for the patient management.


Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Desoxicitidina , Disartria , Femenino , Fluorouracilo , Humanos , Persona de Mediana Edad , Compuestos Organoplatinos/efectos adversos , Oxaliplatino/efectos adversos , Dolor/tratamiento farmacológico , Parestesia/inducido químicamente , Parestesia/tratamiento farmacológico , Habla
15.
BMJ Case Rep ; 15(2)2022 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-35131793

RESUMEN

Oxaliplatin is a chemotherapeutic agent used in a variety of malignancies such as colorectal cancer and pancreatic cancer. It is a platinum derivative that results in direct cell cytotoxicity with resultant cell death. The most common side effects often noted are neurotoxicity, nausea, vomiting, diarrhoea, hepatotoxicity and myelosuppression. Oxaliplatin induced digital ischaemia and necrosis is a rare side effect that was observed in our patient. In general, digital ischaemia is a rare vascular disorder that is often associated with autoimmune disease. A patient with digital ischaemia due to oxaliplatin will be described in this case report.


Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Humanos , Isquemia/inducido químicamente , Necrosis/inducido químicamente , Compuestos Organoplatinos/efectos adversos , Oxaliplatino/efectos adversos
16.
Oncology (Williston Park) ; 36(2): 115-119, 2022 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-35180339

RESUMEN

Neoadjuvant systemic therapy is a preferred treatment approach for a number of tumor types due to many potential advantages over upfront surgery, including tumor downstaging, early treatment of micrometastatic disease, and providing an in vivo test of tumor biology. For colon cancer, current standard of care is upfront surgery followed by adjuvant systemic therapy in high-risk patients. Concerns about inaccurate radiological staging and tumor progression during preoperative treatment, as well the lack of randomized data demonstrating benefit, are among the reasons for the limited use of neoadjuvant therapy in this disease. Locally advanced colon cancer, defined as primary colon cancer with direct invasion into the adjacent structures or extensive regional lymph node involvement, is not always amenable to pathological complete resection, and when attempted it comes with high incidence of postoperative morbidity and mortality because of the required multivisceral resection. Clinical trials of neoadjuvant chemotherapy for colon cancer to date have been promising with downstaging of disease and higher rates of R0 resection. Here, we report a case of a patient with locally advanced, unresectable, mismatch repair deficient sigmoid colon cancer who was treated with neoadjuvant chemoimmunotherapy followed by surgical resection leading to a complete pathologic response after preoperative systemic chemoimmunotherapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fiebre/sangre , Interleucina-6/sangre , Neoplasias del Colon Sigmoide/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Fiebre/inducido químicamente , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Oxaliplatino/administración & dosificación , Oxaliplatino/efectos adversos , Neoplasias del Colon Sigmoide/patología
17.
Bull Cancer ; 109(6): 642-647, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34657726

RESUMEN

AIM: To investigate the therapeutic effect of Elemene combined with Nedaplatin (ECN) on malignant pleural effusion (MPE) and its adverse reactions. METHOD: A retrospective study was conducted, three hundred and fifty-two patients with MPE were divided into two groups according to different treatment methods. One hundred and eighty-nine patients were given intrathoracic injection of ECN and classified in ECN group; one hundred and sixty-three cases in the Nedaplatin group were given intrathoracic injection of nedaplatin. Routine treatments were used to prevent adverse reactions. RESULT: The effective rate of the ECN group was 57.05%, and that of the Nedaplatin group was 23.08%. The comparison results of adverse reactions between the two groups showed that there was no significant difference in leukopenia, thrombopenia, anemia, vomitting and diarrhea, fever, hepatic damage and renal damage. The level of thoracalgia in the ECN group was higher than that in the Nedaplatin group. There was no significant change in the number of CD8+ T cells between the two groups after treatment. The number of CD4+T cells in the ECN group increased after treatment was higher than the Nedaplatin group after treatment. CONCLUSION: ECN treatment can improve clinical control of MPE with no serious adverse reaction, can effectively reduce the immunosuppressive effect of nedaplatin and enhance the immune function of MPE patients which is worthy of clinical application.


Asunto(s)
Derrame Pleural Maligno , Humanos , Compuestos Organoplatinos/efectos adversos , Derrame Pleural Maligno/tratamiento farmacológico , Estudios Retrospectivos , Sesquiterpenos
18.
J Oncol Pharm Pract ; 28(3): 577-581, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33789524

RESUMEN

OBJECTIVE: This study determined the incidence of hypersensitivity reactions in patients receiving oxaliplatin-based chemotherapy while on H1-receptor antagonists (H1RAs). Prophylaxis for patients receiving oxaliplatin is not currently recommended. H1RAs are used for the treatment of reactions; however, prophylactic H1RAs have not been well-studied. METHODS: This retrospective chart review included patients with solid tumor malignancies who received H1RAs while on oxaliplatin-based chemotherapy between August 1, 2016 and October 31, 2019. RESULTS: Of fifty-one patients, there were four hypersensitivity reactions (8%), most of which were mild, occurred within 60 minutes of the start of the infusion, and did not result in an interruption in treatment. One severe reaction occurred, which required discontinuation of therapy. Forty-two patients (82%) were able to receive at least 9 cycles of oxaliplatin without a reported reaction. CONCLUSION: In this observational study, the incidence rate of hypersensitivity reactions in patients receiving oxaliplatin while on H1RAs was lower than reported in previous literature. Most reactions were mild, and patients were able to continue oxaliplatin-based therapy. With future, randomized controlled trials, H1RAs may prove to be effective in preventing or delaying the onset of hypersensitivity reactions related to oxaliplatin.


Asunto(s)
Antineoplásicos , Hipersensibilidad a las Drogas , Neoplasias , Antineoplásicos/efectos adversos , Hipersensibilidad a las Drogas/epidemiología , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/prevención & control , Humanos , Incidencia , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Compuestos Organoplatinos/efectos adversos , Oxaliplatino/efectos adversos , Estudios Retrospectivos
19.
Anticancer Res ; 42(1): 185-193, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34969724

RESUMEN

BACKGROUND: We hypothesized that perioperative FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) might be used as an alternative to standard FLOT (docetaxel, 5-fluorouracil, leucovorin, and oxaliplatin) in patients with locally advanced oesogastric adenocarcinomas (OGA), particularly those with frailties. PATIENTS AND METHODS: We reviewed the charts of 61 consecutives patients treated with FOLFOX for resectable OGA to estimate overall survival, recurrence-free survival, and safety. RESULTS: The median follow-up was 69.7 (range=3.6-97.9) months. Few patients experienced grade 3 adverse events during the preoperative (n=6; 10%) and postoperative (n=6; 16%) phases. One patient experienced a fatal grade 5 adverse events (cardiogenic shock). Median overall survival was 51.7 months [95% confidence interval (CI)=31.6-93.2 months] and the 5-year survival rate was 44.4% (95% CI=30.3%-57.5%). CONCLUSION: Regarding its comparable efficacy and its favourable toxicity profile, perioperative FOLFOX is a reasonable alternative to FLOT for frail patients with resectable OGA.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/sangre , Adenocarcinoma/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antígeno CA-19-9/sangre , Antígeno Carcinoembrionario/sangre , Supervivencia sin Enfermedad , Docetaxel/administración & dosificación , Docetaxel/efectos adversos , Unión Esofagogástrica/efectos de los fármacos , Unión Esofagogástrica/patología , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Oxaliplatino/administración & dosificación , Oxaliplatino/efectos adversos , Periodo Perioperatorio , Modelos de Riesgos Proporcionales , Neoplasias Gástricas/sangre , Neoplasias Gástricas/patología
20.
JCO Glob Oncol ; 7: 1730-1741, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34936375

RESUMEN

PURPOSE: Cancer incidence is rising in low- and middle-income countries, where resource constraints often complicate therapeutic decisions. Here, we perform a cost-effectiveness analysis to identify the optimal adjuvant chemotherapy strategy for patients with stage III colon cancer treated in South African (ZA) public hospitals. METHODS: A decision-analytic Markov model was developed to compare lifetime costs and outcomes for patients with stage III colon cancer treated with six adjuvant chemotherapy regimens in ZA public hospitals: fluorouracil, leucovorin, and oxaliplatin for 3 and 6 months; capecitabine and oxaliplatin (CAPOX) for 3 and 6 months; capecitabine for 6 months; and fluorouracil/leucovorin for 6 months. Transition probabilities were derived from clinical trials to estimate risks of toxicity, disease recurrence, and survival. Societal costs and utilities were obtained from literature. The primary outcome was the incremental cost-effectiveness ratio in international dollars (I$) per disability-adjusted life-year (DALY) averted, compared with no therapy, at a willingness-to-pay (WTP) threshold of I$13,006.56. RESULTS: CAPOX for 3 months was cost-effective (I$5,381.17 and 5.74 DALYs averted) compared with no adjuvant chemotherapy. Fluorouracil, leucovorin, and oxaliplatin for 6 months was on the efficiency frontier with 5.91 DALYs averted but, with an incremental cost-effectiveness ratio of I$99,021.36/DALY averted, exceeded the WTP threshold. CONCLUSION: In ZA public hospitals, CAPOX for 3 months is the cost-effective adjuvant treatment for stage III colon cancer. The optimal strategy in other settings may change according to local WTP thresholds. Decision analytic tools can play a vital role in selecting cost-effective cancer therapeutics in resource-constrained settings.


Asunto(s)
Neoplasias del Colon , Compuestos Organoplatinos , Capecitabina/efectos adversos , Capecitabina/uso terapéutico , Quimioterapia Adyuvante , Neoplasias del Colon/tratamiento farmacológico , Análisis Costo-Beneficio , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Hospitales Públicos , Humanos , Leucovorina/efectos adversos , Leucovorina/uso terapéutico , Recurrencia Local de Neoplasia , Compuestos Organoplatinos/efectos adversos , Oxaliplatino/uso terapéutico , Sudáfrica/epidemiología
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