METHOD FOR INCREASING CANCER PATIENT'S HAEMOGLOBIN LEVEL

Abstract

The invention relates to the field of medicine, particularly to a method for increasing blood haemoglobin level in a cancer patient. A method for increasing blood haemoglobin level in a cancer patient, wherein a pharmaceutical composition comprising a poloxamer as a pharmacologically active substance is administered before and/or during and/or after a course of the chemotherapy or immunotherapy is provided. Thus, the claimed invention provides such a method for increasing blood haemoglobin level in a cancer patient, implementation of which ensures the achievement of the technical result consisting in normalization and maintaining patient's general physical condition at a level that allows for chemotherapy and immunotherapy courses to be administered and improves patients general physical condition following the treatment of cancer with simultaneous reduction of a toxic effect and side effects on a patients

Claims

1. A method for increasing blood haemoglobin level in a cancer patient, wherein a pharmaceutical composition comprising a poloxamer as a pharmacologically active substance is administered before and/or during and/or after a course of the chemotherapy or immunotherapy.

2. The method according to claim 1, wherein the pharmaceutical composition in the form of a tablet, effervescent tablet, capsule, powder, solution or emulsion is administered.

3. The method according to claim 1, wherein a multiple intravenous or oral administration of the pharmaceutical composition is performed.

4. The method according to claim 1, wherein a poloxamer with the concentration of 1-28 wt % is used in a formulation of the pharmaceutical composition.

5. The method according to claim 1, wherein a poloxamer-188 is used in a formulation of the pharmaceutical composition.

Description

[0035] Example 1. Increase in the haemoglobin level during the treatment of multiple myeloma by oral administration of the pharmaceutical composition comprising 13.3 wt % poloxamer before and during a course of the chemotherapy.

[0036] Patient G., man, 70 years of age. Diagnosis: progressive diffuse-nodular multiple myeloma of the stage IIIB. Myelogenic nephropathy, stage III CKD, terminal stage. Chronic programmed dialysis. The initial level of haemoglobin was 72 g/l. The receiving of EPO 20000 IU and iron preparations was prescribed for a month, as a result of which the level of haemoglobin increased to 84 g/l. However, the patient's condition worsened, and there were diagnosed acute transmural myocardial infarction and weight loss in the patient. The patient was prescribed the administration of 30 ml of the sterile pyrogen-free aqueous solution of the poloxamer comprising 13.3 wt % poloxamer-188 (Emuxol-268 of Grade “A”) and water for injection as the remaining part for 30 days. The level of haemoglobin was 116 g/l. Then, 30 ml of the said poloxamer solution was administered to the patient on a daily basis during 9 courses of chemotherapy (cyclophosphan and boramilane), while EPO and iron preparations were no longer prescribed. The level of haemoglobin was maintained in the range of 116-125 g/l.

[0037] Example 2. Increase in the haemoglobin level during the treatment of locally advanced or metastatic bladder cancer of the 4-.sup.th stage with lumbar vertebral metastases by oral administration of the pharmaceutical composition comprising 4 wt % poloxamer during a course of the immunotherapy and after a course of the immunotherapy.

[0038] Patient A., man, 66 years of age. Diagnosis: locally advanced or metastatic bladder cancer of the 4t.sup.h stage with lumbar vertebral metastases. The initial level of haemoglobin was 129 g/l.

[0039] Immunotherapy 1: the patient underwent a course of the therapy with the nivolumab preparation (Opdivo) for 4 months. Donated red blood cells were regularly transfused to increase the level of haemoglobin. After performed therapy, the level of haemoglobin dropped to 123 g/l. Said immunotherapy 1 resulted in a slight progress of treatment.

[0040] Immunotherapy 2: the patient underwent a course of the therapy with the nivolumab preparation (Opdivo) for 5 months with the daily administration of 50 ml of the sterile pyrogen-free aqueous solution of a poloxamer comprising 4 wt % poloxamer-188 (Emuxol-268 of Grade “A”) and water for injection as the remaining part. Following administration of the said pharmaceutical composition of a poloxamer, the level of haemoglobin increased from 123 g/l to 136 g/l. As a result of immunotherapy 2 patient's general condition improved significantly, and there were no anxiety symptoms. Administration of immunotherapy during the administration of the pharmaceutical composition comprising a poloxamer resulted in a better response to immunotherapy, and, which is also important, the immunotherapy proceeded without toxic complications.

[0041] Example 3. Increase in the haemoglobin level during the treatment of chronic lymphocytic leukaemia by oral administration of an emulsion of perfluoroorganic compounds comprising 4.0 wt % poloxamer before a course of the chemotherapy.

[0042] Patient B., man, 71 years of age. Diagnosis: chronic lymphocytic leukaemia. The initial level of haemoglobin was 92.0 g/l. The chemotherapy was not prescribed due to the low haemoglobin value. Iron preparations did not lead to an increase in haemoglobin level. 15 ml of the perfluoroorganic compound based emulsion comprising 4.0 wt % poloxamer-188 (Emuxol-268 of Grade “A”), 13.5 wt % perfluorodecalin, 6.5 wt % perfluoromethylcyclohexylpiperidine, 0.6 wt % sodium chloride, 0.09 wt % potassium chloride and water for injection as the remaining part was administered to the patient during 21 days without the use of other standard treatment preparations. The level of haemoglobin was 101 g/l. Based on the result of anemia treatment, a course of the chemotherapy with bendamustine was carried out.

[0043] Example 4. Increase in the haemoglobin level during the treatment of chronic lymphocytic leukaemia by intravenous administration of the pharmaceutical composition comprising 4 wt % poloxamer during a course of the chemotherapy.

[0044] Patient C., woman, 59 years of age. Diagnosis: chronic lymphocytic leukaemia. The initial level of haemoglobin was 118.0 g/l. For the prophylaxis of anaemia caused by chemotherapy, 10 ml of the sterile pyrogen-free aqueous solution of a poloxamer comprising 4 wt % poloxamer-188 (Kolliphor P188), 0.6 wt % sodium chloride and water for injection as the remaining part was administered to the patient simultaneously with a course of the bendamustine chemotherapy. The level of haemoglobin was 122.0 g/l. The patient underwent a course of the chemotherapy without complications.

[0045] Example 5. Increase in the haemoglobin level during the treatment of right kidney tumor with metastases by intravenous administration of the pharmaceutical composition comprising 6 wt % poloxamer after a course of the immunotherapy.

[0046] Patient D., woman, 58 years of age. Diagnosis: right kidney tumor with metastases T2N1M1. Coronary heart disease. The initial level of haemoglobin was 148 g/1. A course of the immunotherapy with the nivolumab preparation (Opdivo) was prescribed. After 1 course, the level of haemoglobin reduced to 104 g/l. For the treatment of immunotherapy induced anaemia, 20 ml of the pyrogen-free aqueous solution of a poloxamer comprising 6 wt % poloxamer-188 (Emuxol-268 of Grade “A”) and water for injection as the remaining part was administered to the patient during 90 days without the use of other standard treatment preparations. The level of haemoglobin was 130 g/l. Exacted diagnosis: right kidney tumor T1N1M0.

[0047] Example 6. Increase in the haemoglobin level during the treatment of pancreatic cancer IIB by intravenous administration of the pharmaceutical composition comprising 6 wt % poloxamer during a course of the chemotherapy.

[0048] Patient E., man, 61 years of age. Diagnosis: non-metastatic pancreatic cancer IIB. The initial level of haemoglobin was 104 g/l. A course of the chemotherapy with gemcitabine preparation was prescribed. During the entire course of the chemotherapy the patient was administered with 20 ml of the sterile pyrogen-free aqueous solution of a poloxamer comprising 6 wt % poloxamer-188 (Kolliphor P188) and water for injection as the remaining part. The level of haemoglobin was 112 g/l. After receiving of the above pharmaceutical composition during a course of the chemotherapy for 3 months, the pancreatic injury was not observed.

[0049] Example 7. Increase in the haemoglobin level during the treatment of lymphocytic leukaemia by oral administration of the pharmaceutical composition comprising 13.3 wt % poloxamer before, during or after a course of the chemotherapy.

[0050] Patient F., man, 65 years of age. Diagnosis: lymphocytic leukaemia. The initial level of haemoglobin was 104 g/l. The chemotherapy was not prescribed due to the low blood haemoglobin level in the patient. Receiving of iron preparations did not lead to an increase in haemoglobin level. 15 ml of the sterile pyrogen-free aqueous solution of a poloxamer comprising 13.3 wt % poloxamer-188 (Lutrol F 68) and water for injection as the remaining part was administered to the patient during 14 days without the use of other standard treatment preparations. After receiving of the above pharmaceutical composition, the level of haemoglobin was 113 g/l. Based on the result of anemia treatment, a course of the chemotherapy with bendamustine preparation was carried out with daily administration of 15 ml of the sterile pyrogen-free aqueous solution of a poloxamer comprising 13.3 wt % poloxamer-188 (Lutrol F 68) and water for injection as the remaining part. After a course of the chemotherapy with daily administration of the poloxamer preparation, the level of haemoglobin was 114 g/l. For further increasing of haemoglobin level, the above aqueous solution of the poloxamer was administered to the patient during 60 days. As a result the level of haemoglobin increased to 129 g/l.

[0051] Example 8. Increase in the haemoglobin level during the treatment of metastatic pancreatic cancer with liver metastases by oral administration of the pharmaceutical composition comprising 16.6 wt % poloxamer during and after a course of the chemotherapy.

[0052] Patient H., woman, 57 years of age. Diagnosis: metastatic pancreatic cancer with liver metastases. The initial level of haemoglobin was 107 g/l. A course of the chemotherapy with gemcitabine and abraxane was prescribed, and 10 ml of the sterile pyrogen-free aqueous solution of a poloxamer comprising 16.6 wt % poloxamer-188 (Emuxol-268 of Grade “N”) and water for injection as the remaining part was administered to the patient for 30 days. Following the use of the above pharmaceutical composition, the level of haemoglobin was 112 g/l. As a result of receiving the above pharmaceutical composition during a course of the chemotherapy there was no pancreatic injury, while significant regression of liver metastases was observed. For further increasing of haemoglobin level, 10 ml of the sterile pyrogen-free aqueous solution of the poloxamer comprising 16,6 wt % poloxamer-188 (Emuxol-268 of Grade “A”) and water for injection as the remaining part was administered to the patient for 60 days. As a result the level of haemoglobin increased to 132 g/l.

[0053] Example 9. Increase in the haemoglobin level during the treatment of third stage cervical cancer by oral administration of the pharmaceutical composition comprising 28 wt. % poloxamer during a course of the chemotherapy.

[0054] Patient I., woman, 74 years of age. Diagnosis: third stage cervical cancer. Coronary heart disease. The initial level of haemoglobin was 91 g/l. For the prophylaxis of anaemia caused by chemotherapy course, 10 ml of the sterile pyrogen-free aqueous solution of a poloxamer comprising 28 wt % poloxamer-188 (Kolliphor P188), 0.6 wt % sodium chloride and water for injection as the remaining part was administered to the patient during the entire course of the chemotherapy (paclitaxel). The level of haemoglobin following chemotherapy was 110 g/l.

[0055] The study conducted revealed that the level of blood haemoglobin in human have increased following intravenous and oral administration of pharmaceutical compositions comprising a poloxamer, furthermore, the inventors did not find any side effects due to receiving of said compositions.

[0056] The present invention is illustrated by the above examples, which are not intended to limit in any way the subject matter of the present invention. Course duration for administration of the pharmaceutical composition comprising a poloxamer according to the present method is determined by a physician and may encompass a quite wide time range. The minimum course for administration of the said composition is 14 days, and the maximum course for administration of the above-described pharmaceutical composition may last during the entire course of the chemotherapy or immunotherapy, and each unit dose may comprise a poloxamer in the range of 500-5000 mg.

[0057] Thus, the claimed invention provides such a method for increasing blood haemoglobin level in a cancer patient, implementation of which ensures the achievement of the technical result consisting in normalization and maintaining patient's general physical condition at a level that allows for chemotherapy and immunotherapy courses to be administered and improves patient's general physical condition following the treatment of cancer with simultaneous reduction of a toxic effect and side effects on a patient's body.