Preliminary investigation of intraperitoneal raltitrexed in patients with gastric cancer

Abstract

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.

Electrochemistry Study of Antineoplastic Raltitrexed Oxidation Mechanism and its Interaction with DNA

“…Based on the results from all the electrochemical experiments discussed above, a mechanism for the oxidation of RTX can be proposed, Scheme , which is in close agreement with the RTX structure and chemical properties . Moreover, the folic acid oxidation mechanism was used as model for a better understanding the oxidation mechanism of RTX.…”

“…Antimetabolites are substances largely used in the treatment of cancer because they inhibit the biosynthesis of DNA and RNA components, stopping the cell division cycles and the growth of tumors . Raltitrexed (TOMUDEX, RTX), (2S)‐2‐[(5‐{methyl [(2‐methyl‐4‐oxo‐1, 4‐dihydroquinazolin‐6‐yl) methyl] amino}thiophen‐2‐yl) formamido] pentanedioic acid, Scheme , is a folate analogue antimetabolite, which resulted from an extensive research effort to produce a novel direct and specific thymidylate synthase (TS) inhibitor, that was proposed as an alternative to the antineoplastic 5‐fluorouracil . Polyglutamylation of RTX increases its intracellular retention, and the inhibition of the enzyme TS by RTX‐polyglutamate derivatives exceeds 100 times the monoglutamate .…”

“…Raltitrexed (TOMUDEX, RTX), (2S)‐2‐[(5‐{methyl [(2‐methyl‐4‐oxo‐1, 4‐dihydroquinazolin‐6‐yl) methyl] amino}thiophen‐2‐yl) formamido] pentanedioic acid, Scheme , is a folate analogue antimetabolite, which resulted from an extensive research effort to produce a novel direct and specific thymidylate synthase (TS) inhibitor, that was proposed as an alternative to the antineoplastic 5‐fluorouracil . Polyglutamylation of RTX increases its intracellular retention, and the inhibition of the enzyme TS by RTX‐polyglutamate derivatives exceeds 100 times the monoglutamate . Note that TS is the enzyme responsible for the synthesis of thymidine triphosphate (TTP), a nucleotide necessary for DNA synthesis, and that the inhibition of TS causes DNA damage, chromosome aberrations and, consequently, cell death .…”

“…Polyglutamylation of RTX increases its intracellular retention, and the inhibition of the enzyme TS by RTX‐polyglutamate derivatives exceeds 100 times the monoglutamate . Note that TS is the enzyme responsible for the synthesis of thymidine triphosphate (TTP), a nucleotide necessary for DNA synthesis, and that the inhibition of TS causes DNA damage, chromosome aberrations and, consequently, cell death .…”

“…RTX has antineoplastic activity for several kinds of solid cancer tumors, such as gastric , head and neck , malignant mesothelioma and pancreatic , but its main application is in the treatment of advanced colorectal cancer tumor, treatment which has been approved in several countries (not in the United States) .…”