RU2372089C2 - Method of treating patients suffering from colorectal cancer with liver metastases - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention concerns medicine, namely oncology and can be used in treatment of patients with colorectal cancer with multiple liver metastases. The first stage of treatment involves neoadjuvant oxalyplatine chemotherapy; in addition Tomudex is introduced in a dose 3 mg/m² as a 24 hour continuous infusion. After termination of chemotherapy, biotherapy involves intra-arterial injection of Avastin in a dose 10 mg/kg of body weight within 2 hours, neoadjuvant intra-arterial chemotherapy and biotherapy totals in 4-6 courses. At the second stage 4 weeks after chemotherapy surgery is performed. The third stage involves 4-6 courses of adjuvant intra-arterial chemotherapy and biotherapy, as at the first stage.

EFFECT: invention allows increasing survival rate and life expectancy of the patients owing to improved respectability of metastases and lower toxicity of complex neoadjuvant and adjuvant intra-arterial chemotherapy and biotherapy.

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Description

The invention relates to medicine, namely to oncology, and can be used to treat patients with colorectal cancer with multiple liver metastases.

The treatment of malignant tumors is one of the most pressing problems of clinical oncology. Surgical resection of the liver was the only method to achieve long-term survival in case of colorectal cancer metastases in the liver. However, currently in the treatment of metastatic colorectal cancer using various schemes and methods of drug therapy. About 90% of patients with metastases of colon cancer in the liver are not subject to surgical treatment.

A known method of treating patients with colorectal cancer with liver metastases, which consists in the use of drug therapy (D.A. Granov, P.G. Tarazov, X-ray endovascular interventions in the treatment of malignant tumors of the liver, St. Petersburg, Foliant, 2002, S. 171 )

However, the known method is ineffective and is accompanied by severe toxic manifestations.

A known method of treating patients with colorectal cancer with liver metastases, which consists in the intravenous use of oxaliplatin at a dose of 85 mg / m ² , 5-fluorouracil at a dose of 500 mg / m ² and leucovarin at a dose of 20 mg / m ² (Modern oncology. Results of the use of oxaliplatin with colorectal cancer and other solid tumors (according to ASCO No. 2, t.6, 2004, p.99)).

However, the known method is ineffective and is accompanied by a high frequency of side effects.

The closest technical result achieved (prototype) is a method of treating patients with colorectal cancer with liver metastases, which consists in the intra-arterial administration of oxaliplatin at a dose of 150 mg / m ² in the form of a 12-hour continuous infusion and 5-fluorouracil in the form of a 120-hour continuous infusion at a dose of 1000 mg / m ² per day to a total dose of 6-7 g, lasting 4 courses of intra-arterial infusion with an interval of 28 days (RF patent No. 2297219).

However, the known method is ineffective against unresectable metastases of colorectal cancer in the liver.

The authors propose a new effective method for treating patients with multiple metastases of colorectal cancer in the liver, increasing the level of resectability, survival and life expectancy of patients based on complex phased treatment.

The technical result of the proposed method for the treatment of patients with colorectal cancer with multiple liver metastases is to increase the effectiveness of treatment by increasing the resectability, survival and life expectancy of patients with multiple metastases of colorectal cancer in the liver, an integrated approach to the treatment of neoadjuvant and adjuvant chemotherapy.

The technical result is achieved by the fact that non-adjuvant intra-arterial chemotherapy and biotherapy are carried out by additional administration of Tomudex at a dose of 3 mg / m ² in the form of a 24-hour continuous infusion, after chemotherapy Avastin is administered intra-arterially - 10 mg / kg of the patient’s weight, the duration of treatment consists of 4- 6 courses of intra-arterial infusion, then 4 weeks after the end of chemotherapy, an operation is carried out followed by 4-6 courses of adjuvant intra-arterial chemotherapy and biotherapy.

The proposed method of treatment is as follows.

The treatment is carried out in stages:

Stage 1 - 4-6 courses of neoadjuvant intraarterial chemotherapy + biotherapy.

Stage 2 - surgical treatment in the amount of liver resection.

Stage 3 - 4-6 courses of adjuvant intra-arterial chemotherapy + biotherapy.

The first stage - conducting polychemotherapy + biotherapy includes angiography to determine the anatomical version of the hepatic artery. A catheter is inserted into the common hepatic artery according to Seldinger. Under local anesthesia under aseptic X-ray conditions, the femoral artery is punctured. A metal conductor is passed through the lumen of the needle into the femoral artery, and then into the aorta. After removing the needle through the conductor, an angiographic catheter with a pre-modeled inner end is carried out in the aorta, which selectively catheters the celiac trunk by installing a catheter in the common hepatic artery followed by angiography. After angiography, the type of arterial blood supply to the liver is determined. Long-term chemotherapy is carried out through the catheter by a single regiogar intraarterial injection of drugs into the common hepatic artery: 1 day - Oxaliplatin - 150 mg / m ² for a 12-hour continuous infusion, then Tomudex - 3 mg / m ² for a 24-hour continuous infusion, and after chemotherapy is completed, Avastin is administered intra-arterially - 10 mg per 1 kg of the patient’s weight for 2 hours. After each course of neoadjuvant intra-arterial chemotherapy, the results of treatment are evaluated by ultrasound (ultrasound), computed tomography (CT), ciliakography, cancer-embryonic antigen (CEA), carbohydrate antigen (Ca - 19.9). Treatment consists of 4-6 courses of prolonged intra-arterial infusion.

The first stage allows you to transfer the patient from an unresectable state to a resectable one (significant liver damage is considered when metastases involve more than 70% of the liver parenchyma, 6 or more segments, the mouth of 3 main hepatic veins, low functional reserves of the liver are affected). It is the neoadjuvant drug antitumor treatment that gives a real chance to increase resectability among patients with colorectal cancer metastases in the liver.

The second stage is to conduct surgery in the amount of liver resection. The operation is performed 4 weeks after the end of chemotherapy.

Carry out a laparotomy from the double-lobe access by CALNE in the modification (Mercedes) Revision. Lymphatic dissection of the gates of the liver is performed and the right or left bile duct, the right or left hepatic artery and vein are isolated and bandaged in the Glisson gate of the liver. After ligation, the hepatic triad is crossed. Then mobilize the right or left lobe of the liver with the intersection of the ligamentous apparatus of the liver, with the allocation of the suprahepatic segment of the inferior vena cava. 3 short hepatic veins are ligated sequentially, the right or left superior hepatic veins are isolated and ligated. After the appearance of the demarcation line on the diaphragmatic surface of the liver with an electrocoagulator, a line of liver resection is outlined.

Consistently by the fissural method along the intended line, the liver is dissected with ligation of the intrahepatic tubular structures of the liver. Hemostasis by stitching and plasma treatment of the wound surface of the liver with argon or a tachacomb plate. The area of operation is drained by passive drains.

The third stage is carried out 3-4 weeks after discharge of the patient.

The third stage is carried out by analogy with the first, i.e. polychemotherapy and biotherapy are carried out, including administration of drugs intraarterially once - Oxaliplatin at a dose of 150 mg / m ² in the form of a 12-hour continuous infusion, Tomudex - 3 mg / m ² in the form of a 24-hour continuous infusion, and after chemotherapy - Avastin is intra-arterial in a dose of 10 mg per 1 kg of patient weight for 2 hours.

Clinical example.

Patient Blazhko Nikolay Andreevich 10.06.51 g. (55 years old), Barnaul. Diagnosis: C-r sigmoid colon 4 tbsp. T4N2M1 MTS to the liver. Combined treatment. Operation: 06/10/05, Extended obstructive left-sided hemicolectomy. During the audit, multiple metastases in both lobes of the liver with damage to S1, S2, S3, S4, S5, S8. GD: No. 1889 dated 06/16/05 U / D ADC with invasion of all layers. MTS in 4 l / sigmoid mesentery. MTS to the liver. After the operation, 5 B / A.H.T courses were performed according to the Oxaliplatin regimen at a dose of 150 mg / m ² in the form of a 12-hour continuous infusion, Tomudex - 3 mg / m ² in the form of a 24-hour continuous infusion and after the end of each chemotherapy course - Avastin intraarterially at a dose of 10 mg per 1 kg of patient weight.

During control ultrasound, CT, celiacography, metastatic nodes in the liver decreased by more than 50%, and two nodes were not visualized at all, there was a complete regression of these nodes. The patient is transferred from an unresectable state to a resectable one. 11/30/06, Extended left-sided hemihepatectomy. Cholecystectomy Audit. In S2 - 3 × 4 cm, in S4 with the transition to S5 MTS up to 5 cm. 6-7 segments are left. No. 3185 dated 12/05/06, U / D ADK with extensive necrosis, pathomorphism - 3 st. The patient as a result of the treatment with initially unresectable metastases of colorectal cancer in the liver achieved a pronounced cytoreductive effect and thus increased the level of resectability.

In the postoperative period after liver resection, 4 courses of intra-arterial chemobiotherapy were performed. Oxaliplatin + Tomudex + Leucovarin + Avastin (10 mg / kg). With a control ultrasound of the abdominal cavity and liver, CT scan of the abdominal cavity and liver, there is no data for tumor recurrence.

According to the claimed method treated 4 patients. All patients had multiple liver metastases. The treatment was carried out according to the claimed method and the effectiveness of the method was 15%.

Thus, the claimed method is highly effective by increasing the level of resectability of patients with primarily unresectable liver metastases; preoperative intra-arterial multi-course antitumor drug therapy is not accompanied by a significant increase in the frequency of complications and mortality after liver resection.

Claims (1)

A method of treating patients with colorectal cancer with multiple liver metastases, including intra-arterial regional administration of oxaliplatin at a dose of 150 mg / m ² in the form of a 12-hour continuous infusion into the common hepatic artery, characterized in that neoadjuvant chemotherapy with oxaliplatin is carried out at the first stage of treatment, additionally Tomudex is administered at a dose of 3 mg / m ² in the form of a 24-hour continuous infusion; after chemotherapy is completed, avastin biotherapy is carried out intraarterially at a dose of 10 mg / kg of the patient’s weight for 2 hours, in total they carry out 4-6 courses of neoadjuvant intra-arterial chemotherapy and biotherapy, at the second stage, 4 weeks after chemotherapy, surgical treatment is carried out, at the third stage, 4-6 courses of adjuvant intra-arterial chemotherapy and biotherapy are carried out as in the first stage.