RESUMEN
5-Fluorouracil (5-FU) is dosed by body surface area, a practice unable to reduce the interindividual variability in exposure. Endorsed by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT), we evaluated clinical evidence and strongly recommend TDM for the management of 5-FU therapy in patients with colorectal or head-and-neck cancer receiving common 5-FU regimens. Our systematic methodology provides a framework to evaluate published evidence in support of TDM recommendations in oncology.
Asunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Monitoreo de Drogas/normas , Fluorouracilo/efectos adversos , Internacionalidad , Oncología Médica/normas , Antimetabolitos Antineoplásicos/administración & dosificación , Congresos como Asunto/normas , Monitoreo de Drogas/métodos , Fluorouracilo/administración & dosificación , Humanos , Oncología Médica/métodos , Países BajosRESUMEN
AIM: It is known that the neutrophil-to-lymphocyte ratio(NLR)is associated with outcomes in patients with cancer. In this study, changes in the NLR and soluble programmed death-1 ligand-1(sPD-L1)levels were assessed in patients with metastatic colorectal cancer treated with chemotherapy. METHODOLOGY: Ten patients with unresectable metastatic colorectal cancer were administered chemotherapy from January 2005 to April 2017 at the Niitsu Medical Center Hospital. The NLR was calculated based on complete blood counts obtained prior to the administration of chemotherapy. Serum sPD-L1 levels were measured by enzyme-linked immunosorbent assay. NLR and sPD-L1 level changes from baseline were compared with tumor response and tumor markers. RESULTS: A relationship was found between sPD-L1 levels and NLR after the treatment of metastatic colorectal cancer(r=0.241, p=0.0459). Decreased sPD-L1 levels were associated with reduced NLR and tumor marker levels. Increased sPD-L1 levels were not related to elevated tumor marker levels. CONCLUSION: Changes in the NLR and sPD-L1 levels during chemotherapy may have a uniquely predictive value in patients with CRC treated with chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antígeno B7-H1/análisis , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Recuento de Leucocitos , Linfocitos , Masculino , Persona de Mediana Edad , Neutrófilos , SolubilidadRESUMEN
AIM: In order to determine if the changes in the neutrophil-to-lymphocyte ratio(NLR)can predict the timingof regimen alteration, the outcome of chemotherapy for metastatic colorectal cancer was analyzed retrospectively. METHODOLOGY: Thirty patients with unresectable metastatic colorectal cancer were administered chemotherapy from January 2005 to December 2015 at the Niitsu Medical Center Hospital. The NLR was calculated from complete blood counts obtained prior to administration of chemotherapy and at the time of the best response. We defined the period with an NLR≤2.5 as the total interval of an NLR≤2.5. The role of the NLR in overall survival was determined by univariate and multivariate Cox regression models. RESULTS: The median overall survival was 27 months in patients with an NLR≤2.5(n=22)and 11 months in those with an NLR>2.5 (n=8)at the best response(p<0.001). The period with an NLR≤2.5 was found to correlate with overall survival(p<0.001). The patients who survived for more than 3 years were introduced to a second-line treatment prior to achievingan NLR>2.5. The period with an NLR≤2.5(p=0.001)and prechemotherapy CA19-9(p<0.0001)were independent, significant predictors of better survival in multivariate analysis. CONCLUSION: The introduction of a new chemotherapeutic regimen prior to achievingan NLR>2.5 predicted better survival in patients with mCRC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Linfocitos/citología , Neutrófilos/citología , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estudios RetrospectivosRESUMEN
AIM: The impact of neutrophil-to-lymphocyte ratio(NLR)changes on the outcome of chemotherapy for metastatic colorectalcancer (mCRC)was analyzed retrospectively. METHODOLOGY: Twenty seven patients with unresectable mCRC were administered chemotherapy from January 2005 to December 2014 at the Niitsu Medical Center Hospital. The NLR was calculated from complete blood counts obtained prior to the administration of chemotherapy and at the best response. We defined the period with NLR≤2.5 as the totalintervalof NLR≤2.5. The impact of NLR on overallsurvivalwas determined using univariate and multivariate Cox regression models. RESULTS: The median overall survival was 26 months in patients with an NLR≤5(n= 22), and 11 months in those with an NLR>5(n=5)before chemotherapy(p=0.03). The median overall survival was 31 months in patients with an NLR≤2.5(n=19), and 11 months in those with an NLR>2.5(n=8)at the best response(p< 0.001). The period with an NLR≤2.5 was found to correlate with overall survival(p<0.001). The period with an NLR≤2.5 was the only independent, statistically significant predictor of better survival in multivariate analysis(p=0.001). CONCLUSION: The change of NLR may be a dynamic predictor of better survivalin patients with mCRC.
Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Linfocitos , Neutrófilos , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Estudios RetrospectivosRESUMEN
AIM: The effect of individual dose adjustment of 5-fluorouracil (5-FU) based on pharmacokinetic monitoring on the outcome of FOLFOX for metastatic colorectal cancer was analyzed retrospectively. METHODOLOGY: Twenty patients with metastatic colorectal cancer underwent FOLFOX chemotherapy from January 2005 to December 2013 at the Niitsu Medical Center Hospital. The sample group included 11 patients in whom 5-FU doses were adjusted individually based on pharmacokinetic monitoring according to an algorithm to maintain the area under the curve (AUC) in the range of 20-25 mg·h/L (Group A) and 9 patients in whom 5-FU doses were adjusted conventionally based on body surface area (Group B). RESULTS: The objective response rate was 63% and 33% in Group A and Group B, respectively (p=0.174). The median overall survival was 34 months and 14 months in Group A and Group B, respectively (p=0.036). There were 4 cases of Grade 3 toxicity (2 in Group A, 2 in Group B; p=0.636) and no cases of Grade 4 toxicity or treatment-related death. CONCLUSION: Pharmacokinetically guided dose adjustment of 5-FU may improve the outcome of FOLFOX for metastatic colorectal cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/patología , Femenino , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Compuestos Organoplatinos/uso terapéutico , Neoplasias del Recto/patología , Recurrencia , Estudios RetrospectivosRESUMEN
A 6 1-year-old man with unresectable multiple hepatic metastases after resection of sigmoid colon carcinoma was treated with irinotecan and infused 5-fluorouracil (5-FU) plus Leucovorin (FOLFIRI). Since the levels of tumor markers increased, the 5-FU dose was increased from 2,700 to 3,000 mg/m2 using a Jackson-type pump and an extended infusion time of 53 hours. The blood level of 5-FU was 507 ng/mL 16 hours after starting the infusion. The pump was then changed to a bottle-type pump with the same dose of 3,000 mg/m2. At 16 hours, the 5-FU level was 964.5 ng/mL. The areas under the concentration vs. time curve (AUC mgã»h/L)were 21 and 44 mgã»h/L for the Jackson- and bottle-type pumps, respectively. Owing to the development of Grade 3 stomatitis and hand-foot syndrome, 5-FU was reduced to 2,700 mg/m2 with a bottle-type pump. The AUC decreased to 27 mgã»h/L, but the liver metastases were reduced and the adverse effects subsided to Grade 1. This case shows that individual dose adjustment of 5-FU to the appropriate AUC based on pharmacokinetic monitoring of the blood 5-FU level can improve the response, reduce adverse effects, and have a clinical benefit.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fluorouracilo/administración & dosificación , Bombas de Infusión , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias del Colon Sigmoide/tratamiento farmacológico , Esquema de Medicación , Elastómeros , Humanos , Infusiones Intravenosas , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Polímeros , Neoplasias del Colon Sigmoide/patologíaRESUMEN
BACKGROUND/AIMS: Ribonucleotide reductase M1 (RRM1) is a key molecule for gemcitabine resistance. This study evaluated the immunohistochemical expression of RRM1 in resected specimens of intrahepatic cholangiocarcinoma (ICC) and investigated the efficacy of gemcitabine-based neoadjuvant chemotherapy in relation to RRM1 expression in tumors. METHODOLOGY: A retrospective analysis was conducted on 34 consecutive Japanese patients who underwent resection of ICC. Of the 34 patients, 2 were treated with neoadjuvant chemotherapy consisting of gemcitabine 800mg/m2 every 2 weeks to address extrahepatic tumor extension. Expression of RRM1 in tumor specimens was assessed using immunohistochemistry and was classified as either positive or negative. RESULTS: RRM1-positive expression was detected in 19/34 (56%) tumor specimens. Two patients were treated with gemcitabine-based neoadjuvant chemotherapy; one had a tumor specimen showing RRM1-positive expression and showed a 14% tumor reduction rate (stable disease); another patient had a tumor showing RRM1-negative expression and showed a 68% tumor reduction rate (partial response). Surgical procedures planned before administration of neoadjuvant chemotherapy were performed in both patients. CONCLUSIONS: Neoadjuvant chemotherapy with gemcitabine for locally advanced ICC was well tolerated and did not impair planned surgical resections. Tumor expression of RRM1 may determine the efficacy of gemcitabine-based chemotherapy for patients with ICC.
Asunto(s)
Colangiocarcinoma/enzimología , Neoplasias Hepáticas/enzimología , Ribonucleótido Reductasas/metabolismo , Adulto , Anciano , Neoplasias de los Conductos Biliares , Conductos Biliares Intrahepáticos , Biomarcadores de Tumor/análisis , Distribución de Chi-Cuadrado , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Femenino , Humanos , Técnicas para Inmunoenzimas , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Tasa de Supervivencia , Tomografía Computarizada por Rayos XRESUMEN
An 18-year-old woman was admitted to our hospital with pain in the right upper quadrant of the abdomen and fever. Diagnostic imaging studies, namely, upper gastrointestinal roentogenography and endoscopy, were performed, and an oval cystic tumor was detected in the second part of the duodenum. On the basis of the characteristic findings of the imaging studies and blood tests, we established a definitive diagnosis of duodenal duplication complicated with acute pancreatitis, even before surgical exploration. On surgical examination, the main pancreatic duct appeared to communicate internally with the cystic lesion. The histopathological examination of the surgical specimen confirmed the accuracy of the preoperative diagnosis.
Asunto(s)
Duodeno/anomalías , Enfermedad Aguda , Adolescente , Duodenoscopía , Duodeno/diagnóstico por imagen , Duodeno/patología , Duodeno/cirugía , Femenino , Humanos , Pancreatitis/complicaciones , RadiografíaRESUMEN
AIMS: The aim of this study was to evaluate the effect of surgical procedures on the serum levels of 5-fluorouracil (5-FU) in patients undergoing S-1 treatment for pancreaticobiliary malignancy. METHODOLOGY: From January 2003 through December 2008, 27 chemotherapy-naive patients who underwent a surgical procedure for pancreaticobiliary malignancy received S-1 chemotherapy for unresectable or recurrent disease. The primary site of disease was: the extra hepatic bile duct (n=10); gallbladder (n=8); pancreas (n=6); or ampulla of Vater (n=3). The surgical procedure was: pylorus-preserving pancreaticoduodenectomy (PPPD) (n=6); combined major hepatic and bile duct resection (n=6); bilioenteric anastomosis (n=4); or exploratory laparotomy (n=11). S-1 (80-120 mg/day) was administered orally twice daily for 28 days, followed by 14 days without therapy. Subsequently, the serum levels of 5-FU were measured using the HPLC-UV method. RESULTS: The median number of cycles administered per patient was 6 (range, 2-13). Although grade 3 watery eye developed in one patient, neither grade 4 toxicities nor treatment-related deaths were observed. The overall response rate was 19%, the median overall survival time was 9 months, and the 1-year cumulative survival rate was 11%. The maximum levels of 5-FU in the sera of individual patients differed significantly according to the surgical procedure (Kruskal-Wallis test; p=0. 0049); the patients who underwent PPPD had the highest 5-FU levels, as compared with the other patients (Mann-Whitney test; p= 0.003). CONCLUSIONS: The type of operative procedure appears to influence the serum levels of 5-FU in S-1-treated surgical patients with pancreaticobiliary malignancy. Given the possibility of elevated levels of 5-FU in the sera of patients who are treated with S-1 after PPPD, adverse events must be monitored carefully in this cohort.
Asunto(s)
Neoplasias del Sistema Biliar/tratamiento farmacológico , Neoplasias del Sistema Biliar/cirugía , Fluorouracilo/sangre , Ácido Oxónico/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/métodos , Tegafur/uso terapéutico , Anciano , Antimetabolitos Antineoplásicos/uso terapéutico , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Information concerning the pulmonary toxicity of oxaliplatin with infusional 5-fluorouracil plus leucovorin (FOLFOX) is very limited. We herein report the case of a patient with FOLFOX-induced interstitial pneumonia. An 82-year-old man with unresectable colon cancer liver metastases was referred to our department for chemotherapy with the FOLFOX protocol. After the administration of ten cycles, he visited our outpatient clinic with a 2-week history of coughing and shortness of breath; he was afebrile. A chest radiograph showed reticular shadows with ground-glass opacities mainly involving the middle and lower zones of the right lung. Computed tomography depicted ground-glass opacities with superimposed reticulation in the right lung. A diagnosis of FOLFOX-induced interstitial pneumonia was made based on the clinical course and imaging findings. The symptoms disappeared within 3 days after the cessation of the FOLFOX regimen and the initiation of high-dose corticosteroid treatment. Two months after the initiation of the corticosteroid treatment, complete remission of the radiological abnormalities was confirmed; thereafter, interstitial pneumonia did not recur despite the reintroduction of 5-fluorouracil/leucovorin alone, suggesting that 5-fluorouracil/leucovorin alone was not responsible for the development of the interstitial pneumonia. Thus, oxaliplatin, alone or in combination with 5-fluorouracil/leucovorin, may have caused the interstitial pneumonia in this patient. Once interstitial pneumonia has occurred, cessation of the regimen is mandatory, and high-dose corticosteroid treatment is commonly given to rescue patients from this potentially lethal complication.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/inducido químicamente , Corticoesteroides/uso terapéutico , Anciano de 80 o más Años , Neoplasias del Colon/secundario , Fluorouracilo/efectos adversos , Humanos , Leucovorina/efectos adversos , Neoplasias Hepáticas/secundario , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Masculino , Compuestos Organoplatinos/efectos adversos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Serum levels of 5-fluorouracil(5-FU)were measured in a patient receiving pharmacokinetic modulation chemotherapy( PMC), with 5-FU, as well as a combination of oxaliplatin and infusional 5-FU plus leucovorin(FOLFOX). A 77- year-old man presented with unresectable multiple hepatic metastases after abdominoperineal resection of rectal / carcinoma, and was successfully treated by PMC. The patient initially received infusional 5-FU at 750 mg/m(2) once a week, and showed a partial response. Serum 5-FU levels were higher at night, and the peak concentration of 5-FU was / 398 ng/mL. After 13 months of PMC, second-line chemotherapy with FOLFOX was initiated because new liver metastases had appeared. After 4 cycles of FOLFOX4, progression was observed, and the concentration profile of 5-FU / was measured. The area under the concentration vs. time curve(AUC ngxh/mL)was smaller with FOLFOX4 than with PMC, so the FOLFOX6 regimen was tried instead. The AUC increased and disease progression was suppressed. This case shows that individual adjustment of the dose and regimen based on pharmacokinetic monitoring can increase the clinical benefit of fluorouracil.
Asunto(s)
Monitoreo de Drogas , Fluorouracilo/farmacocinética , Fluorouracilo/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fluorouracilo/sangre , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Neoplasias del Recto/sangre , Neoplasias del Recto/cirugía , Tomografía Computarizada por Rayos XRESUMEN
We report that team-based medical care has an important role in tailor made chemotherapy for colorectal cancer. We organized a chemotherapy support team to facilitate the early detection of toxicity and to get hold of therapeutic needs in individual patients. We also measured the circadian variation of 5-fluorouracil plasma concentrations to permit tailor dosed chemotherapy. To date, the chemotherapy support team has managed the performance of pharmacokinetic modulating chemotherapy in 30 patients with unresectable or recurrent colorectal cancer. The median survival time was 19 months after the first-line chemotherapy and 14 months after the second-line treatment. Our results suggest that team-based medical care is practically useful for tailor made chemotherapy in patients with colorectal cancer.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Atención al Paciente , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Neoplasias Colorrectales/psicología , Esquema de Medicación , Femenino , Alimentos , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
AIMS: The present study was conducted to evaluate the effects of irinotecan plus gemcitabine(IRINOGEM)on biliary malignancies. METHODOLOGY: From January 2005 through January 2007, 15 consecutive patients with chemotherapy- naive, locally advanced or metastatic biliary malignancies were enrolled. The primary affected sites were the gallbladder( n=7), extrahepatic bile ducts(n=5), and intrahepatic bile ducts(n=3). All the patients received starting doses of gemcitabine at 250 mg/m /(2) and irinotecan at 25 mg/m(2) given once per 2-week cycle. In the event of progressive disease, the dosage was increased for subsequent cycles. RESULTS: The median number of cycles administered was 16(range, 4-24 cycles)per patient. Although one case of grade 3 neutropenia was noted, neither grade 4 toxicities nor treatment-related deaths were observed. The overall response rate was 40% and the median overall survival time was 8 months, with a 1-year cumulative survival rate of 28%. CONCLUSIONS: IRINOGEM shows promising antitumor activity, and may be a worthwhile treatment option for locally advanced or metastatic biliary malignancies.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Biliar/tratamiento farmacológico , Camptotecina/análogos & derivados , Desoxicitidina/análogos & derivados , Anciano , Neoplasias del Sistema Biliar/patología , Camptotecina/efectos adversos , Camptotecina/uso terapéutico , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Femenino , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , GemcitabinaRESUMEN
AIMS: Pharmacokinetic modulating chemotherapy (PMC) is designed to boost high serum 5-fluorouracil (5-FU) concentrations via modulation by uracil. The aim of this study was to evaluate the efficacy of PMC as a second-line chemotherapy for postresectional recurrences of colorectal carcinoma. METHODOLOGY: Thirteen patients with unresectable recurrences of colorectal carcinoma were treated with PMC as the second-line chemotherapy, after 5-FU or its derivatives as the first-line chemotherapy. PMC was initiated with a 400 mg combination of uracil and tegafur daily and a 24-hour continuous intravenous infusion of 600 mg/m(2) 5-FU once weekly. The 5-FU dose was increased as the disease progressed. RESULTS: Six (46%) of the 13 patients exhibited a partial response (PR) to PMC, based on the RECIST criteria. PR was achieved in 2 of 5, 2 of 5, and 2 of 3 patients undergoing oral administration of 5-FU derivatives, intravenous infusion of 5-FU/l-leucovorin and hepatic-artery infusion of 5-FU, respectively. The median survival time of the 13 patients was 17 months.Grade-2 toxicity was found only in 2 patients. CONCLUSIONS: Because PMC is chronomodulating, it is an effective and safe treatment for recurrent colorectal carcinoma. PMC with a dose increase of 5-FU is recommended as a promising second-line regimen for unresectable colorectal carcinoma resistant to 5-FU.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Ganglios Linfáticos/patología , Neoplasias del Recto/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Cronoterapia , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Esquema de Medicación , Combinación de Medicamentos , Femenino , Fluorouracilo/administración & dosificación , Humanos , Infusiones Intravenosas , Leucovorina/administración & dosificación , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Tasa de Supervivencia , Tegafur/administración & dosificación , Uracilo/administración & dosificaciónRESUMEN
Cardiotoxicity is a rare complication occurring during 5-fluorouracil (5-FU) treatment for malignancies. We herein report the case of a 70-year-old man with 5-FU-induced cardiotoxicity, in whom a high serum level of alpha-fluoro-beta-alanine (FBAL) was observed. The patient, who had unresectable colon cancer metastases to the liver and lung, was referred to us for chemotherapy from an affiliated hospital; he had no cardiac history. After admission, the patient received a continuous intravenous infusion of 5-FU (1000 mg/day), during which precordial pain with right bundle branch block occurred concomitantly with a high serum FBAL concentration of 1955 ng/ml. Both the precordial pain and the electrocardiographic changes disappeared spontaneously after the discontinuation of 5-FU. As the precordial pain in this patient was considered to have been due to 5-FU-induced cardiotoxicity, the administration of 5-FU was abandoned. Instead, oral administration of S-1 (a derivative of 5-FU), at 200 mg/day twice a week, was instituted, because S-1 has a strong inhibitory effect on dihydropyrimidine dehydrogenase, which catalyzes the degradative of 5-FU into FBAL. The serum FBAL concentration subsequently decreased to 352 ng/ml, the same as the value measured on the first day of S-1 administration. Thereafter, no cardiac symptoms were observed. The patient achieved a partial response 6 months after the initiation of the S-1 treatment. The experience of this case, together with a review of the literature, suggests that FBAL is related to 5-FU-induced cardiotoxicity. S-1 may be administered safely to patients with 5-FU-induced cardiotoxicity.
Asunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Neoplasias del Colon/sangre , Neoplasias del Colon/tratamiento farmacológico , Fluorouracilo/efectos adversos , Ácido Oxónico/uso terapéutico , Tegafur/uso terapéutico , beta-Alanina/análogos & derivados , Anciano , Neoplasias del Colon/patología , Combinación de Medicamentos , Electrocardiografía , Corazón/efectos de los fármacos , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Masculino , beta-Alanina/sangreRESUMEN
AIMS: Pharmacokinetic modulating chemotherapy (PMC) is designed to boost high serum 5-fluorouracil (5-FU) concentrations through modulation by uracil. The therapeutic efficacy of PMC and the sensitivity of metastatic lesions to 5-FU were evaluated in advanced colorectal cancer patients. METHODOLOGY: Thirteen patients with colorectal carcinoma metastases to multiple organs were enrolled. PMC was initiated with a combination of 400 mg of uracil-tegafur daily and 24-hour continuous intravenous infusion of 600 mg/m2 of 5-FU once weekly. The 5-FU dose was escalated when the disease progressed. When PR was achieved, serum 5-FU concentrations were monitored in order to evaluate the chemosensitivity of each metastatic lesion to 5-FU. RESULTS: PR in the target lesion was observed in 7 of 11, 6 of 10, 2 of 2, and 2 of 4 patients with metastatic lesions to the liver, lungs, peritoneum and lymph nodes, respectively. The area under the concentration-time curve (AUC ng x hr/ml) of the 5-FU sufficient to induce PR in pulmonary lesions, 3528 to 9684, was significantly higher than for hepatic lesions, 2413 to 6323 (p = 0.028). The median survival was 13 months. CONCLUSIONS: PMC, having a chronomodulating nature, is highly effective in treating colorectal carcinoma metastases with a superior safety profile. Pulmonary metastases are more resistant to 5-FU than hepatic metastases, as they require a higher 5-FU AUC to respond.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cronoterapia , Neoplasias Colorrectales/patología , Bombas de Infusión Implantables , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Combinación de Medicamentos , Femenino , Fluorouracilo/administración & dosificación , Humanos , Infusiones Intraarteriales , Leucovorina/administración & dosificación , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Tegafur/administración & dosificación , Uracilo/administración & dosificaciónRESUMEN
Pharmacokinetic modulating chemotherapy (PMC) is a new therapeutic regimen for advanced colorectal carcinoma, in which high serum 5-FU concentrations are attained through the inhibition of 5-FU degradation by simultaneously administered uracil. A 67-year-old woman, presented with unresectable multiple hepatic and pulmonary metastases following abdominoperineal resection of rectal carcinoma, was successfully treated by the PMC. The patient was initially treated by 600 mg/m2/day of 5-FU infusion, once a week, and subsequently 5-FU doses were increased to 750 mg/m2/day and then to 1,200 mg/m2/day. Hepatic metastases responded at the dose of 750 mg/m2/day and pulmonary metastases responded at the dose of 1,200 mg/m2/day. The patient remains partial response (>21 months). 5-FU serum concentrations were higher at night time and the peak concentration of 5-FU was obtained at 3 a.m. 5-FU Cmax of 600 mg/m2/day, 750 mg/m2/day and 1,200 mg/m2/day were 254, 329, 531 ng/ml, respectively. The experience of this case, together with literature review, suggests that pulmonary metastases are more resistant to 5-FU than hepatic metastases in patients with colorectal carcinoma. The high serum 5-FU concentrations at night suggest the chronomodulating nature of PMC and are effective for metastatic colorectal carcinoma.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias del Recto/patología , Adenocarcinoma/sangre , Adenocarcinoma/secundario , Anciano , Terapia Combinada , Esquema de Medicación , Combinación de Medicamentos , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/sangre , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/secundario , Neoplasias del Recto/cirugía , Tegafur/administración & dosificación , Uracilo/administración & dosificaciónRESUMEN
To clarify the benefit and indication of resection for metastatic liver tumors from gastric cancer, we reviewed the therapeutic outcomes at the Niigata University Medical Hospital and at a referred institution. From January 1982 to April 2004, thirty-nine patients with synchronous and 40 with metachronous liver metastases from gastric cancer had been treated. In synchronous cases, forty percent of the patients had many metastatic tumors in bilateral hepatic lobes and the majority of them had advanced gastric cancer with serosal invasion and widely spread of lymphatic metastases. On the other hand, over 70% of metachronous patients had unilobar or scattered bilobar metastases and only 20% of them accompanied other types of metastases. A survival analysis showed that the prognoses of patients undergoing hepatic resection were statistically better than other treatments in both synchronous and metachronous cases. And there was no evidence for the benefit of palliative gastrectomy. So we conclude that surgical treatment for hepatic metastases from gastric cancer is a beneficial option if all the lesions including the primary and lymphatic ones can be eradicated in limited candidates of synchronous cases and in more candidates of metachronous cases, especially unilobar and a few scattered bilobar metastases.