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PURPOSE: The study was designed to evaluate the safety and efficacy of adding oxaliplatin to py (CRT) with S-1 in patients with locally advanced rectal carcinoma (LARC). We report here the final results of the study. PATIENTS AND METHODS: Patients with histopathologically confirmed LARC (cT3-T4, any N) were eligible. They received oral S-1 (80â¯mg/m2/day on days 1-5, 8-12, 22-26, and 29-33) and infusional oxaliplatin (60â¯mg/m2/day on days 1, 8, 22, 29) plus radiotherapy (1.8â¯Gy/day, total dose of 50.4â¯Gy in 28 fractions), with a chemotherapy gap in the third week of radiotherapy. Primary endpoint of the study was pathological complete response (pCR) rate. Secondary endpoints were rates of R0 resection, down-staging, cumulative 3-year local recurrence, 3-year disease-free survival (DFS), and toxicity. RESULTS: Forty-five patients were enrolled at six centers in Japan. All patients received CRT, and 44 underwent operation. The pCR rate was 27.3% (12/44). The R0 resection rate was 95.5% (42/44). T-down-staging rate was 59.1% (26/44), and N-down staging rate was 65.9% (29/44); the combined pathological down-staging rate was 79.5% (35/44). There were no grade 4 adverse events, but 11.1% of the patients had grade 3 adverse events. Cumulative 3-year local recurrence rate was 0%. However, 13 (30.0%) patients suffered from distant metastasis, and one patient suffered from secondary esophageal cancer that was unrelated to rectal cancer. Eight patients had lung metastasis, 4 had liver metastasis, and 3 patients died of the metastatic disease. The 3-year DFS rate of the 44 patients was 67.5% (median follow-up 36.3â¯months), and the 3-year overall survival (OS) rate was 93.0% (median follow-up 39.6â¯months). The patients were then divided into the pCR (12 patients) group and non pCR (32 patients) group. The 3-year rate of DFS for each group was 91.7% and 58.1% and that of OS was 100% and 90.3%, respectively. CONCLUSIONS: The study showed a high pCR rate with no severe toxicity, good follow-up results, and good loco-regional control. Therefore, addition of oxaliplatin to preoperative CRT with S-1 in patients with LARC might be feasible and lead to better local control than standard treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Recto/terapia , Adulto , Anciano , Quimioradioterapia , Supervivencia sin Enfermedad , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Oxaliplatino/administración & dosificación , Ácido Oxónico/administración & dosificación , Cuidados Preoperatorios/métodos , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Tegafur/administración & dosificaciónRESUMEN
The correct name of the twelfth author should be ''Yasuhiro Yuasa", and not ''Yasuhiko Yuasa'' as given in the original publication of the article.
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BACKGROUND: S-1 plus cisplatin is a standard regimen for advanced gastric cancer (AGC) in Asia. The ToGA trial established a fluoropyrimidine plus cisplatin and trastuzumab as a standard treatment for human epidermal growth factor receptor 2 (HER2)-positive AGC. In the HERBIS-1 trial, trastuzumab combined with S-1 plus cisplatin showed promising antitumor activity in patients with HER2-positive AGC. However, cisplatin has several important drawbacks, including vomiting and renal toxicity. These disadvantages of cisplatin are prominent in elderly patients. Therefore, we conducted a prospective phase II study of trastuzumab plus S-1 without cisplatin in elderly patients with HER2-positive AGC. METHODS: Patients 65 years or older who had HER2-positive AGC received S-1 orally on days 1-28 of a 42-day cycle and trastuzumab intravenously on day 1 of a 21-day cycle. RESULTS: A total of 51 patients were enrolled. Two patients were ineligible. The full analysis set thus comprised 49 patients. The median age was 71 years (range 65-85). The confirmed response rate was 40.8% (95% CI 27.1-54.6%), and the null hypothesis was rejected. The median follow-up period was 10.6 months. Median overall survival was 15.8 months. Median progression-free survival was 5.1 months, and time to treatment failure was 4.0 months. Major grade 3 or 4 adverse events included neutropenia (12.0%), anemia (24.0%), diarrhea (10.0%), and anorexia (12.0%). There was one treatment-related death. CONCLUSIONS: Trastuzumab in combination with S-1 alone demonstrated promising antitumor activity and manageable toxic effects as well as promising survival results in elderly patients with HER2-positive AGC. CLINICAL TRIALS REGISTRATION: UMIN000007368.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/mortalidad , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Combinación de Medicamentos , Femenino , Humanos , Masculino , Ácido Oxónico/administración & dosificación , Ácido Oxónico/efectos adversos , Estudios Prospectivos , Receptor ErbB-2/biosíntesis , Neoplasias Gástricas/mortalidad , Tegafur/administración & dosificación , Tegafur/efectos adversos , Trastuzumab/administración & dosificación , Trastuzumab/efectos adversosRESUMEN
Background: The incidence and characteristics of gastric cancer have been shown to vary widely across Western and Eastern countries. Our study had two aims: to evaluate long-term trends in gastric adenocarcinoma in Japan over a period of 70 years, and to anticipate the future of gastric cancer in Japan, through comparison with data from the United States. Methods: Japanese patient data for 19,306 incident cases of gastric adenocarcinoma from 1946 - 2014 were collected from the Gastric Cancer Database at the Cancer Institute Hospital, Tokyo, Japan (CIH-GCDB). U.S. patient data for 78,625 incident cases of gastric cancer from 1973 - 2012 were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Changes over time in patient and tumor characteristics were investigated in these two cohorts. Results: There was a marked reduction of cancer incidence in the lower third of the stomach in the CIH-GCDB; over 70% to around 30%. The incidence in the upper third has been increasing steadily over time; 3% to 19%, although the number of cardia tumors has not changed. An increase in elderly and obese patients was also noted. In the U.S. population, there was a significant difference in the primary site across races. A notable overall increase in cardia cancer was evident in the Western population during the study period, with no similar change evident in the Japanese population over the last 15 years. In the East Asian population, the proportional frequency of tumors in the cardia was lower and that of tumors in the pyloric antrum was higher. Conclusion: In Japan, cancer in the antrum or pylorus of the stomach has been declining, whereas cancer in the body has been increasing. Unlike the Western population in the United States, adenocarcinoma of esophago-gastric junction is not increasing in Japan.
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INTRODUCTION: Primary tumor location is a critical prognostic factor in metastatic colorectal cancer (mCRC); however, it remains unclear whether tumor location is a predictor of the response to cetuximab treatment. It is also uncertain if BRAF mutation contributes to the impact of tumor location on survival. We assessed the prognostic impact of tumor location on clinical outcomes in mCRC patients treated with first-line cetuximab chemotherapy. PATIENTS AND METHODS: The associations of tumor location with overall survival and progression-free survival were evaluated in mCRC patients with KRAS exon 2 wild-type tumors who were enrolled onto 2 clinical trials: JACCRO CC-05 of cetuximab plus FOLFOX (n = 57, UMIN000004197) and CC-06 of cetuximab plus SOX (n = 61, UMIN000007022). Tumors proximal or from splenic flexure to rectum were defined as right-sided or left-sided, respectively. In addition, exploratory RAS and BRAF mutation analyses were performed. RESULTS: A total of 110 patients were assessable for tumor location; 90 had left-sided tumors. Left-sided tumors were significantly associated with longer overall survival (36.2 vs. 12.6 months, hazard ratio = 0.28, P < .0001) and progression-free survival (11.1 vs. 5.6 months, hazard ratio = 0.47, P = .0041) than right-sided tumors; similar results were obtained in multivariate analysis. A subanalysis showed that the association was evident in the FOLFOX group and that tumor location was an independent prognostic factor irrespective of BRAF status in RAS wild-type patients. CONCLUSION: Primary tumor location might be a predictor of survival independent of BRAF status in mCRC patients who receive first-line cetuximab combined with oxaliplatin-based chemotherapy.
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Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Cetuximab/administración & dosificación , Neoplasias Colorrectales/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: Retrospective studies have found that early tumor shrinkage (ETS) and depth of response (DpR) are associated with favorable outcomes in patients with metastatic colorectal cancer (mCRC); however, few prospective studies have evaluated ETS and DpR. PATIENTS AND METHODS: We performed a phase II study of FOLFOX plus cetuximab as first-line treatment in Japanese patients with KRAS wild-type mCRC. The primary endpoint was response rate (RR), and secondary endpoints included progression-free survival (PFS), overall survival (OS), chronological tumor shrinkage (evaluated every 8 weeks), and safety. The association of ETS and DpR with survival time was analyzed using Spearman's rank correlation coefficient. RESULTS: In 54 participants, the RR, median PFS, and OS were 66.7 % (95 % CI, 53.4-77.8 %), 11.1 months, and 33.9 months, respectively. There was no unexpected toxicity. Forty (80 %) of 50 assessable patients had ETS, which was associated with prolonged PFS and OS (11.3 vs. 3.7 months, HR 0.26, p = 0.0003; 42.8 vs. 9.0 months, HR 0.40, p = 0.0279, respectively). Median DpR was 56.3 %. The DpR correlated with OS (r s = 0.314, p = 0.027) as well as post-progression survival (PPS) (r s = 0.366, p = 0.017). Interestingly, DpR was moderately associated with OS and PPS (r s = 0.587, r s = 0.570, respectively) in patients harboring tumors with larger target lesions, but was not associated with OS or PPS in patients with smaller target lesions. FOLFOX plus cetuximab was active as a first-line treatment for Japanese mCRC patients, with no unexpected toxicities. CONCLUSIONS: Our prospective evaluation of chronological tumor shrinkage showed that ETS and DpR correlate with outcomes in patients with KRAS wild-type mCRC who receive cetuximab-based chemotherapy (UMIN000004197).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cetuximab/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Femenino , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Compuestos Organoplatinos/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Investigator-oriented post-marketing clinical trials of anti-cancer agents are faced to financial crisis due to drastic decrease in research-funds from pharmaceutical companies caused by a scandal in 2013. In order to assess the balance of research funds between 2012 and 2014, we made queries to 26 companies manufacturing anti-cancer agents, and only 10 of 26 responded to our queries. Decrease in the fund was observed in 5 of 10, no change in 1, increase in 3 and no answer in 1. Companies showed passive attitude to carry out doctor-oriented clinical trials of off-patent drugs or unapproved drugs according to advanced medical care B program, though some companies answered to proceed approved routines of these drugs if clinical trials showed good results. Most companies declined to make comments on the activity of Japan Agency for Medical Research and Development (AMED), but some insisted to produce good corroboration between AMED and pharmaceutical companies in order to improve the quality of trials. Further corroboration must be necessary for this purpose among researchers, governmental administrative organs, pharmaceutical companies, patients' groups, and mass-media.
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Antineoplásicos/uso terapéutico , Ensayos Clínicos como Asunto , Industria Farmacéutica , Neoplasias , Antineoplásicos/economía , Humanos , Comercialización de los Servicios de Salud , Neoplasias/tratamiento farmacológico , Encuestas y CuestionariosRESUMEN
Several studies have reported that epidermal growth factor receptor (EGFR)-related molecules may serve as predictors of cetuximab treatment for metastatic colorectal cancer (mCRC), such as EGFR gene copy number (GCN), expression of 2 ligands of EGFR, amphiregulin (AREG) and epiregulin (EREG), and EGFR CA simple sequence repeat 1 (CA-SSR1) polymorphism; however, these biomarkers still remain not useful in clinical practice since they have been evaluated using cohorts with patients treated in various settings of chemotherapy. We therefore analyzed associations of mRNA expression of AREG and EREG, EGFR GCN, and CA-SSR1 polymorphism [short (S;≤ 19) / long (L; ≥ 20)] with clinical outcomes in 77 Japanese patients with KRAS exon 2 wild-type mCRC enrolled in phase II trials of FOLFOX (n = 28/57, UMIN000004197) or SOX (n = 49/67, UMIN000007022) plus cetuximab as first-line therapy. High AREG expression correlated with significantly better progression-free survival (median 11.6 vs. 66 months, HR 0.52, P = 0.037); moreover, it remained statistically significant in multivariate analysis (HR: 0.48, P = 0.027). S/S genotype of CA-SSR1 predicted severe skin toxicity (P = 0.040). Patients with both AREG-low and EGFR low-GCN had significantly shorter overall survival than the others (median 22.2 vs. 42.8 months, HR 2.34, P = 0.042). The multivariate analysis showed that molecular status with both AREG-low and EGFR low-GCN was a predictor of worse survival (P = 0.006). In conclusion, AREG mRNA expression and EGFR CA-SSR1 polymorphism predict survival and skin toxicity, respectively, of initial chemotherapy with cetuximab. Our results also suggest potential prognostic value of the combined assessment of AREG and EGFR GCN for first-line cetuximab treatment.
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Antineoplásicos/uso terapéutico , Cetuximab/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Cetuximab/administración & dosificación , Cetuximab/farmacología , Neoplasias Colorrectales/patología , Receptores ErbB/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Resultado del TratamientoRESUMEN
BACKGROUND: Although postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, has become a standard of care for gastric cancer in Japan, nonresponders may suffer from the cost and adverse reactions without clinical benefit. This multicenter exploratory phase II trial was conducted to see whether a chemosensitivity test, the collagen gel droplet embedded culture drug sensitivity test (CD-DST), can adequately select patients for chemotherapy. METHODS: The CD-DST using four different concentrations of 5-fluorouracil was conducted with resected specimens from preregistered patients who underwent gastrectomy with D2 or more extensive lymphadenectomy. Patients who were histopathologically confirmed to have stage II or greater disease without distant metastasis were eligible for final enrollment. All patients underwent protocol-specified adjuvant chemotherapy with S-1. Three-year relapse-free survival was compared between patients determined as sensitive by the CD-DST (responders) and those deemed insensitive (nonresponders). Appropriate cutoff values for in vitro growth inhibition were defined when the hazard ratio for relapse in responders and the log-rank P values were at their minimum. RESULTS: Of the 311 patients enrolled, 14 were ineligible and 27 failed to start the protocol treatment. The CD-DST failed in 64 other patients, and survival analyses were conducted with the remaining 206 patients (39 stage II disease, 155 stage III disease, and 12 stage IV disease). The outcome of patients who were determined to be responders was significantly superior to that of nonresponders regardless of the 5-fluorouracil concentrations, although no differences in clinicopathologic characteristics were observed between the two groups, except for age. CONCLUSIONS: The CD-DST identified those who benefit from adjuvant chemotherapy. It deserves further evaluation in the setting of a prospective randomized trial. ClinicalTrials.gov identifier: NCT00287755.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ensayos de Selección de Medicamentos Antitumorales/métodos , Fluorouracilo/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Supervivencia sin Enfermedad , Combinación de Medicamentos , Resistencia a Antineoplásicos , Femenino , Fluorouracilo/administración & dosificación , Gastrectomía , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Ácido Oxónico/administración & dosificación , Ácido Oxónico/uso terapéutico , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirugía , Tegafur/administración & dosificación , Tegafur/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: The differences in the growth morphology, proliferative ability, and background mucosa of the cancer between Helicobacter pylori (HP)-positive (HP+) gastric cancer (GC) and HP-negative (HP-) GC are still unclear. To clarify the differences, we compared the characteristics of the two types of cancer. METHODS: Of the 91 patients with undifferentiated-type early GC who underwent endoscopic treatment at our hospital between August 2005 and April 2011, 23 HP- GC patients (all of whom had signet ring cell carcinoma measuring 20 mm or less in diameter) and 46 HP+ GC patients with signet ring cell carcinoma measuring 20 mm or less in diameter (out of a total of 68 HP+ GC patients) were enrolled in this study. Endoscopic atrophy and background mucosa were classified according to the updated Sydney system. The proliferative capacity of the cancer was assessed by examining the MIB-1 labeling index. RESULTS: With regard to the growth in the mucosal layer, the proportion of patients with cancer confined to the proliferative zone was significantly higher in the HP- GC group. Moderate or severer atrophy, intestinal metaplasia, mononuclear cell infiltration, and neutrophil infiltration according to the updated Sydney system were significantly commoner in the HP+ GC patients. Also, the MIB-1 labeling index was significantly higher in the HP+ GC group. CONCLUSION: HP+ GC appeared to show a higher proliferative capacity, more extensive spread, and more rapid progression, and inflammation associated with HP infection was suggested to be involved in the proliferation of this type of GC.
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Carcinoma de Células en Anillo de Sello/microbiología , Carcinoma de Células en Anillo de Sello/patología , Infecciones por Helicobacter/complicaciones , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología , Adulto , Anciano , Endoscopía Gastrointestinal , Femenino , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Gastritis Atrófica/complicaciones , Gastritis Atrófica/microbiología , Helicobacter pylori/patogenicidad , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Early-onset gastric cancer is relatively rare. To evaluate the clinicopathological features and surgical outcome of young patients with gastric cancer, this retrospective comparative study was conducted. METHODS: From 2000 to 2010, 4882 patients underwent surgery for gastric adenocarcinoma in our institution. A total of 136 patients under 40 years old were enrolled as the young group, and a total of 1435 patients aged between 60 and 69 were identified as the control group for this study. The patient's characteristics, pathological findings, surgical and clinical outcomes were reviewed, and the risk factors of recurrence were compared between the two groups. RESULTS: Among the young group, patients had significantly fewer comorbidities and postoperative complications. The patient proportion having 7 or more lymph node metastases was higher in the young group (25 %) than in the control group (16 %). The presence of lymph node metastasis was identified as a strong risk factor for recurrence (odds ratio = 4.31) in the young group according to the results of the step-wise logistic regression analysis. Although the disease-specific survival at stage II was relatively better in the young group (p = 0.0439) than in the control group, there were no significant differences in overall survival for all stages. CONCLUSION: Early-onset gastric cancer is likely to present lymph node metastases. The survival rate of gastric cancer in young patients was equivalent to that in patients in their 60s, which is the typical age at onset.
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Adenocarcinoma/patología , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Adulto , Anciano , Estudios de Casos y Controles , Comorbilidad , Femenino , Gastrectomía/efectos adversos , Humanos , Japón , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/mortalidad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: This study was designed to evaluate the safety and efficacy of adding oxaliplatin to preoperative chemoradiotherapy (CRT) with S-1 in patients with locally advanced rectal carcinoma (LARC). PATIENTS AND METHODS: This was a multicenter phase II study in patients with histologically proven clinical stage T3 or T4 (any N, M0) LARC. Patients preoperatively received oral S-1 (80 mg/m(2)/day on days 1-5, 8-12, 22-27, and 29-33) and infusional oxaliplatin (60 mg/m(2) days on 1, 8, 22, and 29) plus radiotherapy (50.4 Gy), with a chemotherapy gap in the third week of radiotherapy. Pathological complete response (pCR) was the primary endpoint. Secondary endpoints included toxicity, compliance, R0 resection rate, and downstaging rate. RESULTS: A total of 45 patients were enrolled at six centers in Japan. All 45 patients received CRT, and 44 underwent operation. A pCR was achieved in 12 (27.3%) of the 44 patients who underwent surgery. Near-total tumor regression was confirmed in 47.7%. There were no grade 4 adverse events, and 11.1% of the patients had grade 3 adverse events. R0 resection was achieved in 95.5% of the patients. CONCLUSION: Preoperative CRT with S-1 plus oxaliplatin had a high pCR rate and a favorable toxicity profile.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/métodos , Neoplasias del Recto/terapia , Adulto , Anciano , Anciano de 80 o más Años , Quimioradioterapia/efectos adversos , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Japón , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Cuidados Preoperatorios , Inducción de Remisión/métodos , Adulto JovenRESUMEN
BACKGROUND: The objective of this phase I study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of preoperative chemoradiotherapy (CRT) with S-1 plus oxaliplatin in patients with locally advanced rectal cancer. METHODS: Patients received radiotherapy in a total dose of 50.4 Gy in 28 fractions. Concurrent chemotherapy consisted of a fixed oral dose of S-1 (80 mg/m(2)/day) on days 1-5, 8-12, 22-27, and 29-33, plus escalated doses of oxaliplatin as an intravenous infusion on days 1, 8, 22, and 29. Oxaliplatin was initially given in a dose of 40 mg/m(2)/week to three patients. The dose was then increased in a stepwise fashion to 50 mg/m(2)/week and the highest dose level of 60 mg/m(2)/week until the MTD was attained. RESULTS: Thirteen patients were enrolled, and 12 received CRT. Dose-limiting toxicity (DLT) occurred in two of six patients (persistent grade 2 neutropenia, delaying oxaliplatin treatment by more than 3 days) at dose level 3; there were no grade 3 or 4 adverse events defined as DLT. The RD was 60 mg/m(2)/week of oxaliplatin on days 1, 8, 22, and 29. Twelve patients underwent histologically confirmed R0 resections, and two out of six patients (33%) given dose level 3 had pathological complete responses. CONCLUSIONS: The RD for further studies is 80 mg/m(2) of S-1 5 days per week plus 60 mg/m(2) of oxaliplatin on days 1, 8, 22, and 29 and concurrent radiotherapy. Although our results are preliminary, this new regimen for neoadjuvant chemoradiotherapy is considered safe and active. TRIAL REGISTRATION: This trial was registered with Clinicaltrials.gov (identifier: NCT01227239 ).
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Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia , Pelvis/efectos de la radiación , Neoplasias del Recto/terapia , Adenocarcinoma/patología , Adulto , Anciano , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Ácido Oxónico/administración & dosificación , Pronóstico , Neoplasias del Recto/patología , Inducción de Remisión , Tegafur/administración & dosificación , Adulto JovenRESUMEN
After a long history of Dark Age of adjuvant chemotherapy for gastric cancer, definite evidences of survival benefit from adjuvant treatment have been reported since 2000s. These survival benefits are likely attributed to something new approach different from pervious studies. In 2001, South West Oncology Group INT0116 trial yielded survival benefit in curatively resected gastric cancer patients with postoperative chemoradiotherapy [5-fluorouracil (5-FU) + Leucovorin + radiotherapy], followed by positive result by MAGIC Trial, employing peri-operative(pre- and postoperative chemotherapy with Epirubicin, cisplatin (CDDP), 5-fluorouracil (ECF) regimen in patients with curative resection. A novel drug [S1: ACTS-GC (Adjuvant chemotherapy trial of TS-1 for gastric cancer) in 2007], or new drug combination chemotherapys [CDDP + 5-FU: FNCLCC/FFCD (Federation Nationale des Centres de Lutte contre le cancer/Federation Francophone de Cancerologie Digestive) in 2011, Capecitabine + Oxaliplatin: CLASSIC in 2012] also produced positive results in terms of improved prognosis. Neoadjuvant or perioperative chemotherapy, novel anti-cancer drugs, and chemoradiotherapy might be the key words to develop further improvement in the adjuvant treatment of resectable gastric cancer. Moreover, it is not new but still true to stress the importance of D2 surgery as the baseline treatment in order to minimize the amount of residual tumor after surgery.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia Adyuvante , Gastrectomía , Terapia Neoadyuvante , Neoplasias Gástricas/terapia , Quimioterapia Adyuvante , Humanos , Neoplasia Residual , Dosis de Radiación , Neoplasias Gástricas/patología , Resultado del TratamientoRESUMEN
PURPOSE: Cisplatin plus 5-fluorouracil has been globally accepted as a standard regimen for the treatment for advanced gastric cancer. However, cisplatin has several disadvantages, including renal toxicity and the need for admission. S-1 plus cisplatin has become a standard treatment for advanced gastric cancer in East Asia. This phase III study was designed to evaluate the potential benefits of adding docetaxel to S-1 without a platinum compound in patients with advanced gastric cancer. METHODS: Patients were randomly assigned to receive docetaxel plus S-1 or S-1 alone. The docetaxel plus S-1 group received docetaxel on day 1 and oral S-1 on days 1-14 of a 21-day cycle. The S-1 alone group received oral S-1 on days 1-28 of a 42-day cycle. The primary end point was overall survival. RESULTS: Of the 639 patients enrolled, 635 were eligible for analysis. The median overall survival was 12.5 months in the docetaxel plus S-1 group and 10.8 months in the S-1 alone group (p = 0.032). The median progression-free survival was 5.3 months in the docetaxel plus S-1 group and 4.2 months in the S-1 alone group (p = 0.001). As for adverse events, neutropenia was more frequent in the docetaxel plus S-1 group, but remained manageable. CONCLUSION: As first-line treatment for advanced gastric cancer, docetaxel plus S-1 significantly improves median overall and progression-free survival as compared with S-1 alone. (ClinicalTrials.gov number: NCT00287768).
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Adenocarcinoma/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/mortalidad , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Anciano , Cisplatino/administración & dosificación , Docetaxel , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Ácido Oxónico/administración & dosificación , Pronóstico , Estudios Prospectivos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Tasa de Supervivencia , Taxoides/administración & dosificación , Tegafur/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: The effectiveness of specific regimens of adjuvant therapy for gastric cancer has not been verified by large clinical trials. Recently, several large trials attempted to verify the effectiveness of adjuvant therapy. The Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer in Japan, a randomized controlled trial of adjuvant S-1 therapy for resected gastric cancer, demonstrated significant improvement in overall and relapse-free survival, compared to surgery alone. To evaluate value for money of S-1 therapy, cost-effective analysis was carried out. METHODS: The analysis was carried out from a payer's perspective. As an economic measure, cost per quality-adjusted life-year (QALY) gained was estimated. Overall survival was estimated by the Kaplan-Meier method, up to 5-year observation. Beyond this period, it was simulated by the modified Boag model. Utility score is derived from interviews with sampled patients using a time trade-off method. Costs were estimated from trial data during observation, while in the period beyond observation they were estimated using simulation results. To explore uncertainty of the results, qualitative and stochastic sensitivity analyses were done. RESULTS: Adjuvant S-1 therapy gained 1.24 QALYs per patient and increased costs by $3,722 per patient for over lifetime (3% discount rate for both effect and costs). The incremental cost-effectiveness ratio (95% confidence intervals) for over lifetime was estimated to be $3,016 ($1,441, $8,840) per QALY. The sensitivity analyses showed the robustness of these results. CONCLUSION: Adjuvant S-1 therapy for curatively resected gastric cancer is likely cost-effective. This therapy can be accepted for wide use in Japan.
Asunto(s)
Antimetabolitos Antineoplásicos/economía , Antimetabolitos Antineoplásicos/uso terapéutico , Ácido Oxónico/economía , Ácido Oxónico/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/economía , Tegafur/economía , Tegafur/uso terapéutico , Adulto , Anciano , Quimioterapia Adyuvante , Terapia Combinada , Análisis Costo-Beneficio , Combinación de Medicamentos , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Años de Vida Ajustados por Calidad de Vida , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Resultado del TratamientoRESUMEN
PURPOSE: The purpose of this multicenter phase II study was to evaluate the efficacy and safety of a combination of irinotecan, 5-fluorouracil (5-FU), and leucovorin (FOLFIRI) plus bevacizumab as first-line chemotherapy in Japanese patients with metastatic colorectal cancer. METHODS: Patients with metastatic colorectal cancer were eligible for enrollment. On day 1 of a 14-day cycle, patients received bevacizumab 5 mg/kg, irinotecan 150 mg/m², and L-leucovorin 200 mg/m² as an intravenous infusion, followed by 5-FU 400 mg/m² as an intravenous bolus and then 5-FU 2,400 mg/m² as an 46-h intravenous infusion. This treatment cycle was repeated. The primary endpoint was progression-free survival (PFS). RESULTS: We enrolled 40 patients, but one withdrew consent before starting treatment. The remaining 39 patients received a total of 509 cycles of FOLFIRI plus bevacizumab (median 11 per patient; range 1-30). The median PFS was 11.5 months, the median overall survival (OS) was 22.0 months, and the 1-year OS rate was 81.8 %. All 39 patients had adverse events. Grade 3 or 4 neutropenia and stomatitis occurred in 21 (53.9 %) and 4 (10.3 %) patients, respectively. CONCLUSION: Our results suggest that FOLFIRI plus bevacizumab is a clinically effective regimen with a manageable toxicity profile as first-line chemotherapy in patients with metastatic colorectal cancer.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/análogos & derivados , Neoplasias Colorrectales/tratamiento farmacológico , Adenocarcinoma/sangre , Adenocarcinoma/secundario , Adulto , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/uso terapéutico , Neoplasias Colorrectales/sangre , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Estudios de Seguimiento , Humanos , Incidencia , Japón/epidemiología , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Leucovorina/uso terapéutico , Leucopenia/inducido químicamente , Leucopenia/epidemiología , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Estomatitis/inducido químicamente , Estomatitis/epidemiología , Análisis de SupervivenciaRESUMEN
A 73-year-old woman underwent esophagogastroduodenoscopy (EGD) at a local hospital, which revealed a flat elevated lesion, approximately 15 mm in diameter, in the posterior wall of the lower gastric body. At our hospital, a repeat EGD and biopsy led to a diagnosis of moderately dysplastic adenoma. The patient requested endoscopic submucosal dissection (ESD). Histopathology revealed a gastric adenoma with negativity for tumor at the vertical margin; however, the horizontal margin was positive for cancer with an undifferentiated carcinoma surrounding the adenoma. EGD was repeated, and a discolored area was found around the ESD scar. Biopsy revealed an undifferentiated carcinoma. Laparoscopic distal gastrectomy was performed, and postoperative histopathology also revealed an undifferentiated carcinoma (50 mm in diameter) surrounding the ESD scar; this lesion was an undifferentiated adenocarcinoma that was colocalized with and spread out to surround the original adenoma. This case is important for consideration of the pattern of development and progression of superficial spreading gastric cancer.
RESUMEN
We experienced a case of gastric cancer that was prospectively followed up for 8 years. With severe heart disease, the patient did not wish surgery or anticancer drug treatment. After informed consent was obtained, he was followed up for 8 years. He received upper gastrointestinal endoscopy every year, which revealed IIc early gastric cancer, and biopsy showed well differentiated adenocarcinoma. A flat and mildly depressed lesion with redness was observed on endoscopy, exhibiting typical morphology of IIc-type early gastric cancer. The appearance of IIc M cancer was observed macroscopically from 2000 to 2003. Four years later, surface irregularity with ulceration appeared. Then, the whole lesion was elevated, which suggested submucosal invasion, and the tumor exhibited the morphology of IIa + IIc or type 3. The ulcer became deeper and elevated boundaries were formed. Horizontal expansion of the flat lesion was mild, while invasion to deeper layers was predominant. Eventually, he died of heart failure. Estimated M cancer was observed for about 3 years, followed by invasion to deeper layers. Taken together, this is a valuable case that followed up the manner of invasion to deeper layers over time from early to advanced gastric cancer.
RESUMEN
PURPOSE: To evaluate the efficacy and safety of the combination of gemcitabine (GEM) and S-1 (GS) in comparison to GEM alone (G) for unresectable pancreatic cancer. METHODS: In this multicenter randomized phase II study, we randomly assigned unresectable pancreatic cancer patients to either the GS group or the G group. The GS group regimen consists of intravenous 1,000 mg/m(2) GEM during 30 min on days 1 and 8, combined with 80 mg/m(2) oral S-1 twice daily on days 1-14, repeated every 3 weeks. On the other hand, the G group regimen consists of intravenous 1,000 mg/m(2) GEM on days 1, 8, and 15, repeated every 4 weeks. The primary endpoint was objective response rate (ORR). Secondary end points included treatment toxicity, clinical response benefit, progression-free survival (PFS), and overall survival. RESULTS: We registered 117 patients from 16 institutions between June 2007 and August, 2010. The ORR of the GS group was 28.3%, whereas that of the G group was 6.8%. This difference was statistically significant (P = 0.005). The disease control rate was 64.2% in the GS group and 44.1% in the G group. Median PFS was 6.15 months in the GS group and 3.78 month in the G group. This was also statistically significant (P = 0.0007). Moreover, the median overall survival (OS) of the GS group was significantly longer than that of the G group (13.7 months vs. 8.0 months; P = 0.035). The major grade 3-4 adverse events were neutropenia (54.7% in the GS group and 22.0% in the G group), thrombocytopenia (15.1% in the GS group and 5.1% in the G group), and skin rash (9.4% in the GS group). CONCLUSIONS: The GS group showed stronger anticancer activity than the G group, suggesting the need for a large randomized phase III study to confirm GS advantages in a specific subset.