Biochemical Modulation of 5-Fluorouracil by Methotrexate in Patients With Advanced Gastric Carcinoma

Pérez, J. Eduardo; Lacava, J.; Dominguez, M. E.; Rodríguez, Ricardo; Barbieri, Mario; Ortíz, Eduardo; Acuña, Luis A. Romero; Langhi, M.; Acuña, Juan; Vallejo, Carlos; Leone, Bernardo Amadeo; Machiavelli, M; Romero, A

doi:10.1097/00000421-199810000-00006

Cited by 11 publications

(10 citation statements)

References 22 publications

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“…Hematological toxicity of bolus infusion of 5-FU is generally greater than that with continuous infusion (26,31,33), and hematological toxicity, particularly neutropenia, in the MF arm was actually more severe than in the 5-FU arm in the present study. The toxicity of MF in the present study was not markedly different from that in the previous Phase II study of MF against peritoneal metastasis (Grade 3 or 4 leukocytes: 16%; Grade 3 or 4 neutrophils: 27%; Grade 3 or 4 hemoglobin: 24%; Grade 3 or 4 bilirubin: 24%; Grade 3 or 4 creatinine: 5%; Grade 3 or 4 diarrhea: 5% and Grade 3 or 4 nausea: 5%) (19).…”

Section: Discussioncontrasting

confidence: 47%

Randomized Phase III Study of 5-Fluorouracil Continuous Infusion vs. Sequential Methotrexate and 5-Fluorouracil Therapy in Far Advanced Gastric Cancer with Peritoneal Metastasis (JCOG0106)

Shirao

Boku

Yamada

et al. 2013

Japanese Journal of Clinical Oncology

103

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Objective: Owing to the risks of serious and sustained toxicity, anticancer drugs such as cisplatin and irinotecan cannot be readily administered to patients with gastric cancer and severe peritoneal metastasis. Therefore, a standard chemotherapy regimen has yet to be established for these types of patients. This randomized study investigated the utility of sequential methotrexate and 5-fluorouracil therapy vs. 5-fluorouracil continuous infusion for gastric cancer with peritoneal metastasis. Methods: Eligible patients had radiologically confirmed peritoneal metastasis with intestinal stenosis, peritoneal tumor or ascites. Treatment with 5-fluorouracil continuous infusion (800 mg/m 2 /day, ci, d1-5, q4w) or methotrexate and 5-fluorouracil therapy (methotrexate, 100 mg/m 2 , bolus infusion, followed 3 h later by 5-fluorouracil, 600 mg/m 2 , bolus infusion, with leucovorin rescue, q1w) was continued until disease progression or unacceptable toxicity. The projected sample size was 236, providing 80% power to detect a 40% increase in median overall survival in methotrexate and 5-fluorouracil therapy with a one-sided a of 0.05. Results: All 237 randomized patients were included in the primary analysis. The methotrexate and 5-fluorouracil therapy arm was not superior to the 5-fluorouracil continuous infusion arm (median survival time, 9.4 months in the 5-fluorouracil continuous infusion arm, 10.6 months in the methotrexate and 5-fluorouracil therapy arm; hazard ratio, 0.94; 95% confidence interval, 0.72 -1.22; one-sided P ¼ 0.31). Frequencies of Grade 3 or higher neutropenia, Grade 3 or higher anorexia and treatment-related deaths were 0.9, 27.4 and 1.7%, respectively, in the 5-fluorouracil continuous infusion arm, and 31.9, 33.6 and 0.9%, respectively, in the methotrexate and 5-fluorouracil therapy arm. Conclusions: Methotrexate and 5-fluorouracil therapy is not suitable for use as standard therapy for advanced gastric cancer with peritoneal metastasis.

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Section: Discussioncontrasting

confidence: 47%

Randomized Phase III Study of 5-Fluorouracil Continuous Infusion vs. Sequential Methotrexate and 5-Fluorouracil Therapy in Far Advanced Gastric Cancer with Peritoneal Metastasis (JCOG0106)

Shirao

Boku

Yamada

et al. 2013

Japanese Journal of Clinical Oncology

103

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“…Sequential MTX/5-FU therapy was effective in a phase II trial for advanced gastric cancer [25,26]. 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].…”

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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“…Recently, sequential MTX/5FU therapy has been reported to be effective in patients with advanced gastric cancers [12,[22][23][24]. The median survival time of advanced gastric cancer patients after this therapy has been reported to be approximately 7 months.…”

Section: Assessment Of Nutritional Statementioning

confidence: 99%

Sequential methotrexate and 5-fluorouracil therapy for gastric cancer patients with peritoneal dissemination: a retrospective study

et al. 2001

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Biochemical Modulation of 5-Fluorouracil by Methotrexate in Patients With Advanced Gastric Carcinoma

Cited by 11 publications

References 22 publications

Randomized Phase III Study of 5-Fluorouracil Continuous Infusion vs. Sequential Methotrexate and 5-Fluorouracil Therapy in Far Advanced Gastric Cancer with Peritoneal Metastasis (JCOG0106)

Randomized Phase III Study of 5-Fluorouracil Continuous Infusion vs. Sequential Methotrexate and 5-Fluorouracil Therapy in Far Advanced Gastric Cancer with Peritoneal Metastasis (JCOG0106)

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

Sequential methotrexate and 5-fluorouracil therapy for gastric cancer patients with peritoneal dissemination: a retrospective study

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