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Cancer metastasis to lymph nodes (LNs) almost certainly contributes to distant metastasis. Elevation of LN internal pressure (intranodal pressure, INP) during tumor proliferation is associated with a poor prognosis for patients. We have previously reported that a lymphatic drug delivery system (LDDS) allows the direct delivery of anticancer drugs into the lymphatic system and is a promising treatment strategy for early‐stage LN metastasis. However, methods for evaluating the treatment effects have not been established. Here, we used a mouse model of MXH10/Mo‐lpr/lpr, which develops a systemic swelling of LNs, and murine malignant fibrous histiocytoma‐like (KM‐Luc/GFP) cells or murine breast cancer (FM3A‐Luc) cells inoculated into the subiliac LN of mice to produce a tumor‐bearing LN model. The changes in INP during intranodal tumor progression and after treatment with cis‐dichlorodiammineplatinum(II) (CDDP) using an LDDS were measured. We found that tumor progression was associated with an increase in INP that occurred independently of LN volume changes. The elevation in INP was suppressed by CDDP treatment with the LDDS when intranodal tumor progression was significantly inhibited. These findings indicate that INP is a useful parameter for monitoring the therapeutic effect in patients with LN metastasis who have been given drugs using an LDDS, which will serve to manage cancer metastasis treatment and contribute to an improved quality of life for cancer patients., Direct delivery of an anticancer drugs into the lymphatic system using a novel lymphatic drug delivery system (LDDS) was an effective treatment for early‐stage lymph node (LN) metastasis in a mouse model. Intranodal pressure (INP) reflects tumor activity in tumor‐bearing LN. Therefore, measurement of INP could be a useful method to evaluate the therapeutic effects of cancer treatment given using an LDDS.

The lymphatic drug delivery system (LDDS) is a new technique that permits the injection of drugs into a sentinel lymph node (SLN) at an early stage of tumor metastasis, thereby treating metastasis in the SLN and its secondary lymph nodes (LNs). The quantity of drug required for a LDDS is much smaller than that needed for systemic chemotherapy. However, the relationship between the rate of drug injection into a SLN and the amount of drug reaching the secondary LNs has not been investigated. In this study, we used an MXH10/Mo-lpr/lpr mouse model to show that the optimal rate for the injection of a fluorescent dye by a LDDS was 10 to 80 μL/min. An injection rate of 10 to 80 μL/min was able to fill the downstream LN. However, an injection rate of 100 μL/min drove the fluorescent dye into the efferent lymphatic vessels and thoracoepigastric vein, decreasing the amount of dye retained in the downstream LN. Bolus injection (defined as an injection rate of 2400 μL/min) was unable to deliver fluorescent dye into the downstream LN. These results agree with the impulse values calculated from the injection pressures in the upstream LN. We anticipate that our findings will facilitate the development of a LDDS for use in the clinic.