DCF intraperitoneal and intravenous dual chemotherapy regimen for advanced gastric cancer: A feasibility study

Abstract

Gastric cancer is the fourth most common type of cancer globally and accounts for the second highest cancer-associated mortality rate in the world. Current treatment strategies for gastric cancer include surgery, radiotherapy, chemotherapy and targeted therapy. Intraperitoneal (IP) chemotherapy may increase the IP concentrations of chemotherapy drugs and reduce the systemic toxicity. At present, IP chemotherapy is used to treat patients with advanced gastric cancer, which has a high rate of peritoneal recurrence. The present study evaluated the feasibility of using docetaxel, cisplatin and fluorouracil (DCF) in an IP and intravenous (IV) dual chemotherapy regimen for the treatment of advanced gastric cancer. The treatment-associated adverse reactions and preliminary efficacy were reported. The first dose level utilized the full dose of DCF: Docetaxel, day one, 45 mg/m2 (IP) and day eight, 30 mg/m2 (IV); cisplatin (DDP), day one, 75 mg/m2 (IP); and fluorouracil (FU), days one to five, 750 mg/m2 (continuous IV). A total of six patients were treated at this level and two patients withdrew due to serious adverse reactions. Taking into account that the the tolerated doses used in combination regimens for Eastern populations are lower than that of the corresponding doses for Western populations, the dosages of the three drugs were all reduced by 20% in the application of the second dose level: Docetaxel, day one, 30 mg/m2 (IP) and day eight, 30 mg/m2 (IV); DDP, day two, 60 mg/m2 (IP); and FU, days one to five, 600 mg/m2 (continuous IV). A total of 26 patients were treated at this level. The main adverse reaction was bone marrow suppression, with grade III/IV neutropenia, leukopenia and febrile neutropenia accounting for 61.5, 53.8 and 19.2% of reactions, respectively, and grade III/IV anemia and thrombocytopenia accounting for 19.2 and 15.4% of reactions, respectively. Gastrointestinal adverse reactions primarily consisted of abdominal pain, with grade III/IV abdominal pain accounting for 30.8% of reactions. Only 7.7% of the patients withdrew from the treatment. The median time to progression (TTP) was five months [95% confidence interval (CI), 1.0–9.0 months], and the median overall survival (OS) was nine months (95% CI, 7.4–10.6 months). It was concluded that the DCF regimen with reduced dosage should be applied. IP and IV dual chemotherapy for the treatment of unresectable advanced gastric cancer is tolerated and demonstrated a good initial efficacy. Strategies for mitigating and reducing the adverse gastrointestinal reactions, particularly abdominal pain, may be the focus of future studies.

Chemotherapy Induces Oral Mucositis in Mice Without Additional Noxious Stimuli

“…In humans 5-FU is administered intravenously except in cases of advanced gastric cancer, where IP administration aims to increase the concentration of chemotherapy in the peritoneal cavity. [31] Thus, it is not surprising that a recently published mouse oral mucositis model spaced IP injections a week apart to reduce abdominal toxicity, while the study presented no histologic evidence of oral ulcers and only a weak oral mucosal inflammatory response, as tissues can recover after lengthy intermissions to 5-FU exposure [9]. Nevertheless, using a high throughput transcriptomic approach this model identified novel genes that may be up- or down-regulated in response to 5-FU in the oral mucosa [9].…”

Nanoparticle-mediated tumor vaccines for personalized therapy: preparing tumor antigensin vivoorex vivo?

“…Compared to chemotherapy and radiotherapy, PDT generates ROS more directly and does not cause severe side effects such as leucopenia and gastrointestinal reactions. 37,38 Thus, PDT can induce tumor cells to produce more DAMPs and are more effective at inducing ICD. 28 Antigen releasing also enhances anti-tumor immune responses.…”

The Effect of the Nano-Drug Carbomicin Inhibiting the Relapse of Stomach Cancer after Radiofrequency Ablation

“…However, thus far, focally injected molecular drugs have not usually maintained an effective concentration for a sufficient amount of time as they are easily absorbed into the blood and lymph capillaries surrounding the RFA focus. Controlled-release nano drugs [28][29][30] are larger [20][21][22][23][24] than the vascular endothelial pores and gaps of the blood and lymph capillaries [25][26][27]. Nano drugs are also characterized by an outstanding residence time in the target tissues [31,32].…”