Sequential methotrexate and 5-fluorouracil in advanced gastric cancer.

Konishi, Toshiro; Mafune, Ken–ichi; Hiraishi, M; Miyama, Takeshi; Hirata, Toru; Mori, Kiyoshi; Idezuki, Yasuo

doi:10.5833/jjgs.23.2024

Cited by 15 publications

(28 citation statements)

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“…In a Japanese phase II trial of sequential MTX/5-FU for patients with advanced gastric cancer, the response rates were reported to be 23% and 41% with low-and intermediate-dose MTX regimens, respectively [27]. Konishi et al [28] reported that the MTX/5-FU regimen showed greater effi cacy in patients with the diffuse type of adenocarcinoma than in those with the intestinal type. The response rate of patients with peritoneal dissemination in their study was 23% (6/26) and ascites was eliminated in 8 of 16 patients (50%).…”

Section: Discussionmentioning

confidence: 99%

Pilot study of a combination of S-1 and paclitaxel for patients with peritoneal metastasis from gastric cancer

et al. 2010

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dissemination still have a poor prognosis [1]; most of these patients die within 6 months of diagnosis, while the 5-year survival rate is nil [2,3].The recent introduction of an oral drug, S-1, has increased the overall response rates (ORRs) to 44% and 49% and median survival time (MST) to 8 months in phase II studies [4,5].Several reports have demonstrated that S-1 was effective for undifferentiated histological types, such as poorly differentiated adenocarcinoma and signet-ring cell carcinoma, which are relevant to peritoneal dissemination [6]. S-1 has been reported to be effective in prolonging the survival of gastric cancer patients with peritoneal dissemination [4][5][6][7].Moreover, S-1 in combination with other anticancer drugs such as cisplatin (CDDP), taxanes, and irinotecan (CPT-11) increased ORRs and prolonged MST [8][9][10][11].Paclitaxel is a cytotoxic antineoplastic agent that causes excessive polymerization of tubulin and microtubule dysfunction, resulting in tumor cell death [12]. Kobayashi et al. [13] have demonstrated that paclitaxel is a promising drug for the treatment of malignant ascites in patients with gastric cancer: the concentration of paclitaxel in ascites was maintained within the optimal level for the treatment of cancer cells for up to 72 h after intravenous administration.Recent phase II studies of systemic chemotherapy with S-1 plus taxanes have demonstrated strong anticancer effects and a good MST in the treatment of advanced gastric cancer [9,10,14]. However, the effi cacy of systemic chemotherapy for peritoneal dissemination from gastric cancer has been unclear, because peritoneal metastases have not been defi ned as measurable lesions in conventional phase II studies. Therefore, few reports describing the effi cacy of chemotherapy for these lesions are available.In this pilot study, we planned therapeutic strategies to observe the effect of chemotherapy on peritoneal metastasis by second-look laparoscopy for patients Abstract Background. This pilot study was carried out to evaluate the effi cacy of chemotherapy for patients with peritoneal dissemination from gastric cancer or positive lavage cytology diagnosed by staging laparoscopy. Methods. Sixteen patients were enrolled. Paclitaxel was administered at 120 mg/m 2 on day 1 and S-1 was administered orally at 80 mg/m 2 for 14 consecutive days, followed by a 1-week rest, as one course. After fi ve courses of this therapy, the primary gastric tumors were evaluated and second-look laparoscopy was performed for patients showing partial response or stable disease with clinical benefi t. Results. Partial response or stable disease with clinical benefi t was confi rmed in seven and fi ve patients, respectively, and these patients underwent second-look laparoscopy. No viable cancer cells were detected on cytopathological investigation during second-look laparoscopy in 9 patients who underwent surgical treatment. The intent-to-treat response rate for gastric tumor was 44% and the rate of disappearance of peritoneal metastasis was 38% ...

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Section: Discussionmentioning

confidence: 99%

Pilot study of a combination of S-1 and paclitaxel for patients with peritoneal metastasis from gastric cancer

et al. 2010

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“…Konishi et al [12] reported that an MTX/5FU regimen showed higher effi cacy in patients with diffuse type of adenocarcinoma than in those with intestinal type. The response rate of patients with peritoneal dissemination in their study was 23% (6/26) and ascites was eliminated in 8 of 16 patients (50%).…”

Section: Discussionmentioning

confidence: 99%

Intraperitoneal administration of paclitaxel and oral S-1 for a patient with peritoneal dissemination and hydronephrosis due to advanced gastric cancer

et al. 2007

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S-1 has been developed in Japan as an oral anticancer drug, composed of tegafur, 5-chloro-2, 4-dihydroxypyridine (gimeracil), and monopotassium 1, 2, 3, 4-tetrahydro-2, 4-dioxo-1, 3, 5-triazine-6-carboxylate (oteracil), based on the biological modulation of 5-fl uorouracil (FU) [5]. Japanese late phase II trials of S-1 in gastric cancer have shown overall response rates of up to 49% and a median survival period of 8 months [6,7]. We have demonstrated that S-1 has a larger area under the curve 5-FU for peritoneal dissemination and ascites than for plasma [8], and thus S-1 might be effective for prolonging the survival of gastric cancer patients with peritoneal metastasis.Paclitaxel is a cytotoxic antineoplastic agent that results in tumor cell death by causing the excessive polymerization of tubulin and microtubule dysfunction [9]. The large molecular weight and bulky chemical structure of paclitaxel delay its peritoneal clearance [10] and increase exposure in the peritoneal cavity, and thus it can be exploited in the treatment of gastric cancer with peritoneal dissemination.We report a gastric cancer patient with peritoneal dissemination and hydronephrosis who was successfully treated with intraperitoneal infusion of paclitaxel and oral administration of S-1. Case reportA 34-year-old man was treated with an H2-blocker antagonist for about 6 months for a chief complaint of upper abdominal discomfort, suggesting the possibility of duodenal ulcer. Because his condition did not improve, he underwent endoscopic examination at another clinic. He was diagnosed as having type 3 advanced gastric cancer on the greater curvature of the gastric body by upper gastrointestinal (UGI) and endoscopic examination. He was referred to a hospital for surgical resection. An abdominal computed tomogra- AbstractWe report a patient with type 3 gastric cancer with peritoneal dissemination and hydronephrosis who was successfully treated with intraperitoneal infusion of paclitaxel and oral administration of S-1. He was diagnosed with unresectable gastric cancer with severe peritoneal dissemination by staging laparoscopy. We selected combined chemotherapy with both paclitaxel and S-1. Paclitaxel at 60 mg/m 2 was administered intraperitoneally on days 1 and 8, and S-1 at 100 mg/body was administered orally for 14 days, followed by 7 days' rest, as one course. After fi ve courses, primary tumor reduction was confi rmed and no cancer cells were detected on pathocytological investigation at second-look laparoscopy. The patient underwent total gastrectomy with lymph node dissection. He died from liver metastasis 29 months after the initial treatment, but he had not suffered from peritoneal metastases and had kept a good quality of life (QOL) since that treatment. This chemotherapy can be applied as one of the promising candidates for the treatment of patients with peritoneal metastasis of gastric cancer.

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“…Thus, careful patient selection might be important for second-line chemotherapy in patients with severe PM. At the time of planning this study, we anticipated that the MST of patients with severe PM was 4-5 months on the basis of previous reports [16][17][18]. Compared with our assumption about the MST in the ''best available 5-FU'' arm (4-6 months), the actual MST with ''best available 5-FU'' was much longer (7.7 months), whereas the MST of the wPTX arm was as long as expected (7.7 months).…”

Section: Discussionmentioning

confidence: 99%

“…The median survival time (MST) for ''best available 5-FU'' was assumed to be 4-6 months [16][17][18], and it was expected that wPTX would prolong survival by a median of 2 ± 0.5 months. The sample size was calculated to be 100 in total, with a one-sided alpha level of 0.3 and power of at least 85 %.…”

Section: Data Management and Statistical Analysismentioning

confidence: 99%

Randomized phase II study of second-line chemotherapy with the best available 5-fluorouracil regimen versus weekly administration of paclitaxel in far advanced gastric cancer with severe peritoneal metastases refractory to 5-fluorouracil-containing regimens (JCOG0407)

Nishina

Boku²,

Gotoh

et al. 2015

Gastric Cancer

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Background This randomized phase II study compared weekly administration of paclitaxel (wPTX) with the best available 5-fluorouracil (5-FU) regimen as second-line treatment for advanced gastric cancer patients with severe peritoneal metastasis refractory to fluoropyrimidine. Methods In the best available 5-FU arm, continuous infusion of 5-FU (800 mg/m 2 /day, days 1-5, every 4 weeks) was given to patients with prior chemotherapy including bolus 5-FU, and methotrexate and 5-FU sequential bolus injection (methotrexate at 100 mg/m 2 followed by bolus 5-FU at 600 mg/m 2 with leucovorin, weekly) was given to those who had previously received continuous infusion of 5-FU or oral administration of fluoropyrimidine. In the wPTX arm, paclitaxel (80 mg/m 2 ) was administered on days 1, 8, and 15, every 4 weeks. This study adopted a screening design (one-sided a = 30 %) with the primary end point of overall survival. Results One hundred patients were randomized to the 5-FU arm (n = 49) or the wPTX arm (n = 51). Although the median survival time was 7.7 months in both arms, the 2-year survival rates were 2.9 % in the 5-FU arm and 9.1 % in the wPTX arm [hazard ratio 0.89 (95 % confidence interval 0.57-1.38), one-sided p = 0.298}. The median progression-free survival was longer with wPTX than with 5-FU [3.7 months vs 2.4 months; hazard ratio 0.58 (95 % confidence interval 0.38-0.88), one-sided The incidences of grade 4 neutropenia, grade 3/4 febrile neutropenia, diarrhea, and treatment-related death were 6 %, 4 %, 10 %, and 2 %, respectively, in the 5-FU arm and 2 %, 0 %, 0 %, and 0 %, respectively, in the wPTX arm. ConclusionsAs second-line chemotherapy, wPTX appears feasible and promising. This regimen can be included in a test arm in future phase III trials for treatment of advanced gastric cancer with severe peritoneal metastasis.

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Sequential methotrexate and 5-fluorouracil in advanced gastric cancer.

Cited by 15 publications

References 0 publications

Pilot study of a combination of S-1 and paclitaxel for patients with peritoneal metastasis from gastric cancer

Pilot study of a combination of S-1 and paclitaxel for patients with peritoneal metastasis from gastric cancer

Intraperitoneal administration of paclitaxel and oral S-1 for a patient with peritoneal dissemination and hydronephrosis due to advanced gastric cancer

Randomized phase II study of second-line chemotherapy with the best available 5-fluorouracil regimen versus weekly administration of paclitaxel in far advanced gastric cancer with severe peritoneal metastases refractory to 5-fluorouracil-containing regimens (JCOG0407)

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