Lung cancer is already stage IV at the time of diagnosis in 50% of patients, losing the opportunity for surgery. Despite the introduction of new chemotherapeutic agents, the improvement in efficacy is extremely limited because there is no major breakthrough in chemotherapy theory [1]. And at this time, chemotherapy is almost the only option. Based on our experience of previous chemotherapy and interventional treatment, we proposed the theory of microcirculatory chemotherapy and used it in clinical practice, which significantly improved the efficacy. Subjects and methods Subjects: 18 patients with stage IIIB and IV non-small cell lung cancer (14 cases of stage IV) who were given chemotherapy or interventional (4 cases) with vincristine (VDS), cisplatin (DDP), mitomycin (MMC), i.e., MVP regimen after tumor E enlargement and aggravation of clinical symptoms such as shortness of breath and cough; 16 males and 2 females, age 39-75 years, mean age (59±10). Among them, 2 cases were postoperative recurrence, 2 cases of Pancostoma, 1 case of peripheral type lung cancer, 13 cases of central type lung cancer (including 1 case of abscess type lung cancer); 12 cases of squamous carcinoma (including 1 case of hypofractionated squamous carcinoma), 3 cases of adenocarcinoma, 1 case of hypofractionated adenosquamous carcinoma, and 2 cases of clinical diagnosis. The tumor diameters ranged from 3 to 11 cm, with a mean of (5.34±1.93) cm. 4 cases had tumors with moderate or above pleural effusion, 3 cases had pericardial effusion, 1 case had paralysis of the recurrent laryngeal nerve, 4 patients with esophageal involvement had significant dysphagia, and 2 cases had tumor invasion of the brachial plexus. Most patients had behavioral status scores between 2 and 3 [2]. METHODS: (1) Treatment regimen: scopolamine (trade name: 654-2, 10-20 mg/dose for intervention and 30 mg/dose for chemotherapy) plus VDS 8 mg, DDP 80 mg/O given in two divided doses on days 1 and 8 of the course, and MMC 10 mg given on day 1 of the course, once every 4 weeks. (2) Administration method: Interventional deepening of venipuncture push via bronchial artery or simple deep venipuncture push administration of chemotherapy. For interventional treatment, 654-2 10~20mg is pushed through bronchial artery first, then chemotherapy drug is pushed; for deep venous puncture route, 654-2 10mg is pushed, then 654-2 20mg is given intravenously. Antiemetics were used before and after conventional chemotherapy, and diuretics were used after chemotherapy. In 11 of the 18 patients in this group, the drug was administered on the first day of the first to third courses of treatment through the interventional route of bronchial artery by femoral artery cannulation; on the eighth day, the drug was administered through the direct vena cava or right atrial injection by subclavian vein puncture. Radiotherapy was added after 3 courses of chemotherapy if the lesions were reduced and more limited. The criteria for determining the efficacy [3]: complete disappearance of the tumor for more than 4 weeks was considered effective (CR); tumor shrinkage of more than 50% in volume for more than 4 weeks without the appearance of new lesions was considered partially effective (PR); tumor shrinkage of less than 50% for more than 4 weeks without the appearance of new lesions was considered ineffective (NC); tumor increase of more than 25% in volume with the appearance of new lesions was considered tumor progression (PD). The patients received 2-6 courses of chemotherapy or interventional therapy (mean about 4.3 courses). 10 of the 18 cases showed significant improvement or disappearance of symptoms, 1 case of CR and 9 cases of PR, among which 1 patient with right lower lobe lung cancer underwent right total pneumonectomy due to ipsilateral recurrence during postoperative chemotherapy, and later developed a left central lung mass with enlarged hilar lymph nodes during chemotherapy, and underwent interventional therapy for left lung mass again. After switching to 654-2 plus interventional and deep vein route chemotherapy, the central mass was quiescent during 3 courses of chemotherapy, but the mass began to shrink 2 months after the cessation of chemotherapy and shrank 60% to meet the PR criteria at 5 months; one case of unresectable giant abscess (no fluid level) One patient with hypofractionated squamous carcinoma, the tumor continued to increase in size during 3 consecutive courses of interventional chemotherapy, with shortness of breath, cough progressively heavier and less sputum. 8 patients with NC and PD died from 53 to 138 d after rechemotherapy, with a mean of (87±41) d. 4 patients with pleural effusion basically disappeared, 1 patient with pericardial effusion had a significant reduction of effusion; 1 patient with laryngeal nerve involvement had a significant improvement of pronunciation and choking symptoms, 4 patients with tumor involvement of esophagus One case of stage IIIB and two cases of stage IV patients received radiotherapy. The adverse effects of chemotherapy were mainly gastrointestinal reactions and leukopenia, with the incidence rates of 94% (17/18) and 83% (15/18), respectively; other more common ones were weakness, wasting and chest pain. Discussion Interventional therapy for lung cancer is theoretically more effective than general chemotherapy because of the formation of higher local drug concentration in the tumor. However, the efficacy of clinical observation is not as satisfactory. The reason may be related to the strong stimulation of chemotherapeutic drugs leading to strong spasm of local blood vessels, which reduces the drug entering into tumor tissues. For this reason, we used microvascular dilating drug 654-2 before and during chemotherapy to release vasospasm, dilate capillaries, and increase vascular permeability and drug concentration in tumor tissues. As a result, chemotherapeutic capillaritis was produced and a large proportion of tumor microvessels were occluded (digital subtraction angiography data showed that after several interventions, tumor vessels would show a “rat tail sign” similar to pulmonary hypertension, which indirectly confirmed the serious damage of microvessels). In our group, after 18 patients failed to be treated with conventional MVP regimen, they were treated with 654-2 plus chemotherapy or interventional therapy, and 10 patients showed positive results. In fully drug-resistant patients, the reduction of tumor size takes longer, about 2 months or even longer. In one patient in our group, the tumor shrank by more than 60% only after 5 months of treatment with this regimen. Lung tissue has dual blood supply from bronchial artery and pulmonary artery. In the course of chemotherapy, two doses, one by bronchial artery intervention and one by subclavian vein route, should theoretically improve the efficacy, and in practice it has been determined to improve the efficacy. For some patients who do not have the conditions for intervention, the latter route alone can be used to inject drugs directly into the superior vena cava or right atrium, which can push several drugs needed for treatment directly into the body within minutes, so that the drugs used can reach peak concentration in the body at the same time, avoiding the interference of external factors during the longer drip of drugs outside the body and improving the efficacy; at the same time, it also avoids peripheral phlebitis. The clinical efficacy of 654-2 plus interventional and chemotherapeutic regimens in the treatment of lung cancer that has failed conventional chemotherapy has been shown to be clinically effective, but the number of cases in this group is small and there is no control group, so the exact effect has to be confirmed by clinical observation in a large sample.