Epirubicin, Cisplatin, and Raltitrexed in Patients With Advanced Gastric and Hepatobiliary Carcinoma

Ferrari, Vittorio; Amoroso, Vito; Valcamonico, Francesca; Fusi, Alberto; Simoncini, Edda; Vasalli, Lucia; Rangoni, G.; Mambrini, Andrea; Marpicati, P.; Montini, E; Marini, G

doi:10.1097/01.coc.0000128722.41587.19

Cited by 8 publications

(8 citation statements)

References 14 publications

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“…Occasional studies have included raltitrexed, a chemotherapeutic drug with a long half-life, in the treatment combination used for intravenous chemotherapy of gastric cancer [ 17 , 18 ]. In those cases, the intravenous dosing regimens range from 1 mg/m 2 to 3 mg/ml 2 and were well tolerated, although one study suggested that there was no substantial antitumor activity using raltitrexed for gastric cancer intravenously [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Preliminary investigation of intraperitoneal raltitrexed in patients with gastric cancer

et al. 2014

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BackgroundPeritoneal implantation metastasis of gastric cancer is the major reason for cancer recurrence after radical operations. As a new chemotherapeutic agent, raltitrexed has been widely used in intravenous chemotherapy for many kinds of cancers. However, no study has reported the efficacy and safety of raltitrexed in intraperitoneal chemotherapy. This study aimed to explore the safety of intraperitoneal chemotherapy with raltitrexed during gastric cancer operation compared to normal saline (NS) rinsing of the abdominal cavity.MethodsIn this prospective study, 91 gastric cancer patients undergoing surgery and reconstruction were consecutively enrolled and randomly assigned into two groups. Raltitrexed in NS (500 ml) was injected into the abdominopelvic cavity for the patients in the RT group (n = 48), while for the patients in the group NS (n = 43), only NS (500 ml) was injected. The postoperative complications, gas passage time, and adverse effects, according to NCI-CTCAE v3.0, were compared between the two groups.ResultsThere were no significant differences in age, sex, cancer pathological type, clinical stage or operation method between the two groups (all P >0.05). No significant difference was observed in adverse effects and postoperative complications between the two groups (all P >0.05). No significant change was found in the levels of red blood cells, white blood cells, platelets, lactate dehydrogenase, blood urea nitrogen, and alanine aminotransferase before and after the operation for both groups (all P >0.05). All adverse events were mild or moderate by NCI-CTCAE v3.0 (National Cancer Institute common terminology criteria for adverse events) grade.ConclusionsThe findings of the present study demonstrate that intraperitoneal chemotherapy with raltitrexed after gastric cancer operation is safe and could be used for patients.

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Section: Introductionmentioning

confidence: 99%

Preliminary investigation of intraperitoneal raltitrexed in patients with gastric cancer

et al. 2014

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“…For cancer patients with f luoropyrimidine-induced cardiotoxicity or a history of cardiac disease, raltitrexed may be a suitable alternative to 5-FU (18). In addition to patients with colorectal cancer, certain patients with advanced gastric cancer have benefited from treatment with raltitrexed and have demonstrated good tolerance to raltitrexed with low cardiac toxicity (21,22). However, the anticancer effect of raltitrexed for advanced gastric cancer remains unknown with regard to the pro-apoptotic mechanisms.…”

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confidence: 99%

Raltitrexed induces mitochondrial-mediated apoptosis in SGC7901 human gastric cancer cells

Xue

Chen

Qin

et al. 2014

Molecular Medicine Reports

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Abstract. Raltitrexed is a specific inhibitor of thymidylate synthase (TS), which has been considered as a potential chemotherapeutic agent for the treatment of advanced gastric cancer. In the present study, the apoptosis mechanisms of raltitrexed in SGC7901 human gastric cancer cells were investigated. The cytotoxic activity of raltitrexed on SGC7901 cells was determined by cell counting kit-8 (CCK-8) assay. The CCK-8 assay indicated that raltitrexed inhibits SGC7901 cell growth in a dose-and time-dependent manner. The morphological changes were observed by fluorescent microscopy, and characteristic morphological changes, including nuclear shrinkage and apoptotic bodies, were observed following Hoechst 33258 staining. The effects on apoptosis, cell cycle, mitochondrial transmembrane potential and reactive oxygen species (ROS) were measured by flow cytometry. The analysis revealed that raltitrexed exerted a growth inhibitory effect by inducing time-dependent apoptosis and cell-cycle arrest at the G 0 /G 1 phase. In addition, a compromised mitochondrial membrane potential and overproduction of ROS demonstrated the involvement of the mitochondrial signaling pathway. Raltitrexed-induced caspase-3-dependent apoptosis was identified using a caspase-3 activity assay and pretreatment with the caspase-3 inhibitor, Ac-DEVD-CHO (sequence, Ac-Asp-Glu-Val-Asp-CHO). The activity of caspase-3 was analyzed with a spectrometer. The protein expression levels of Bax, Bcl-2, cytochrome c, cleaved caspase-3 and TS were examined by western blot and the mRNA expression level of TS was detected by quantitative polymerase chain reaction. The analysis revealed that the protein levels of Bax, cytochrome c and cleaved caspase-3 were significantly increased by raltitrexed, while Bcl-2 expression levels were reduced. Furthermore, raltitrexed increased the expression of the TS protein and mRNA in a time-dependent manner. These results indicate that raltitrexed induces the apoptosis of SGC7901 cells through the caspase-3-dependent mitochondrial signaling pathway and upregulates the expression of the TS protein and mRNA.

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“…The results have been summarized in Table 2. There were two phase I studies (14,15) and four phase II studies (16)(17)(18)(19), although two contain patients in the second-line of treatment. The phase I studies combined raltitrexed, at 3 mg/m 2 every three weeks, with an anthracycline; one study also included cisplatin (14).…”

Section: Discussionmentioning

confidence: 99%

Raltitrexed as a substitute for capecitabine in metastatic gastric cancer: a case report and literature review

Ladak¹,

Preti²,

Dias³

et al. 2022

Ann Transl Med

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Background: 5-Fluorouracil and its oral prodrug, capecitabine, are frequently used in the treatment of gastrointestinal cancers-including gastric cancer-but carry a cardiotoxicity risk. Raltitrexed (brand name Tomudex), a direct inhibitor of thymidylate synthase, has been successfully used as an alternative to fluoropyrimidines in patients with 5-fluorouracil-induced cardiac events. We report the first case, to our knowledge, of raltitrexed used with trastuzumab and platinum-based chemotherapy as a substitute for fluoropyrimidines following cardiotoxicity in a 78-year-old male patient with metastatic gastric cancer.Case Description: The patient experienced a myocardial infarction 3 days after beginning treatment with capecitabine, carboplatin, and trastuzumab for metastatic HER2 + gastric adenocarcinoma. Capecitabine was replaced with raltitrexed, and the patient ultimately received seven cycles of chemotherapy, five of which included raltitrexed. There were no cardiotoxic events attributable to raltitrexed, although the patient did experience hypotensive episodes, premature ventricular contractions, myelosuppression, and anemia. Progression-free survival was 4.5 months, within the expected range achieved with the ToGA regimen (trastuzumab, cisplatin, 5-fluorouracil chemotherapy). At time of writing, the patient has been alive for 48 weeks since diagnosis.Conclusions: In summary, raltitrexed appears to be a safe alternative to fluoropyrimidines when combined with trastuzumab and platinum, although more data is needed to determine its relative effectiveness.

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Epirubicin, Cisplatin, and Raltitrexed in Patients With Advanced Gastric and Hepatobiliary Carcinoma

Cited by 8 publications

References 14 publications

Preliminary investigation of intraperitoneal raltitrexed in patients with gastric cancer

Preliminary investigation of intraperitoneal raltitrexed in patients with gastric cancer

Raltitrexed induces mitochondrial-mediated apoptosis in SGC7901 human gastric cancer cells

Raltitrexed as a substitute for capecitabine in metastatic gastric cancer: a case report and literature review

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