Low doseLow dose c chemotherapy with hemotherapy with insulin (Insulin Potentiation insulin (Insulin Potentiation

Therapy) Therapy) in combination with hormone in combination with hormone

therapy for treatment of therapy for treatment of castration resistant prostate castration resistant prostate

cancercancer

D-r Christo Damyanov, D-r Desislava Gerasimova, D-r Christo Damyanov, D-r Desislava Gerasimova, D-r Ivan Maslev, D-r Veselin GavrilovD-r Ivan Maslev, D-r Veselin Gavrilov

Medical center “Integrative Medical center “Integrative medicine”medicine”

Sofia 2012Sofia 2012

Medical center “Integrative Medical center “Integrative medicine”medicine”

IntroductionIntroduction In spite of the efficacy of standard androgen In spite of the efficacy of standard androgen

deprivation therapy for metastasis tumors of prostate deprivation therapy for metastasis tumors of prostate gland, almost all of the patients progress with their gland, almost all of the patients progress with their diseasedisease

Despite obvious efforts for revealing the reasons for Despite obvious efforts for revealing the reasons for hormonal resistance after androgen deprivation the hormonal resistance after androgen deprivation the treatment remains a challenge.treatment remains a challenge.

Up to 1990 the results after chemotherapy for hormone-Up to 1990 the results after chemotherapy for hormone-resistant tumors of prostate gland are disappointing.resistant tumors of prostate gland are disappointing.

In 2004 two trials registered and prolonged survival In 2004 two trials registered and prolonged survival after using Docetaxel.after using Docetaxel.

At this moment the treatment with Docetaxel in At this moment the treatment with Docetaxel in combination with Prednisone is accepted as standard of combination with Prednisone is accepted as standard of care for metastatic castration resistant prostate tumors care for metastatic castration resistant prostate tumors [5,6].[5,6].

According to our previous experience in According to our previous experience in implementation of IPTLD in different tumors including implementation of IPTLD in different tumors including castration resistant prostate tumors we conducted a castration resistant prostate tumors we conducted a research for new possibilities where our main target research for new possibilities where our main target was to improve the quality of life.was to improve the quality of life.

This study is focusing on the potential of IPTLD in This study is focusing on the potential of IPTLD in combination with hormone therapy for treatment of combination with hormone therapy for treatment of patients with castration resistant prostate tumors.patients with castration resistant prostate tumors.

Patients and methodPatients and method

Between April 2006 to May 2011 a total 406 Between April 2006 to May 2011 a total 406 patients with diverse tumors were treated with patients with diverse tumors were treated with IPTLD and 21 out of them were with prostate IPTLD and 21 out of them were with prostate cancer. Sixteen of them were with advanced cancer. Sixteen of them were with advanced prostate cancer (Stage III – Stage IV and nodal, prostate cancer (Stage III – Stage IV and nodal, bone or visceral secondary) and cynically bone or visceral secondary) and cynically apparent hormonal independence entered the apparent hormonal independence entered the study.study.

The patients were divided into two groups: The patients were divided into two groups: Group AGroup A - 8 patients treated with - 8 patients treated with ЕpirubicinЕpirubicinee, , VinblastiVinblastine, Cyclophosphamide in combination ne, Cyclophosphamide in combination with LHRH agonist (Goserelin depot 3,6mg). with LHRH agonist (Goserelin depot 3,6mg).

Group BGroup B another 8 patients were treated with another 8 patients were treated with Docetaxel in combination with LHRH agonist Docetaxel in combination with LHRH agonist (Goserelin depot 3,6mg). (Goserelin depot 3,6mg).

Patients and methodPatients and methodClinical characteristics of the treated patients

Clinical parametersClinical parameters Group AGroup A Group BGroup B

Total number of patientsTotal number of patients 88 88

Age Age      

Median Median 6464 6666

RangeRange 56-7656-76 53-7353-73

Karnovsky Performance Scale (mean)Karnovsky Performance Scale (mean)      

Median Median 6868 7474

RangeRange 50-8050-80 60-9060-90

Beretta score bifor treatmentBeretta score bifor treatment      

Median Median 2424 2424

RangeRange 10 - 4210 - 42 6 - 336 - 33

Glison scoreGlison score      

44 11 00

55 11 11

66 00 11

77 22 11

88 11 00

99 33 33

UnknownUnknown 00 22

Patients and methodPatients and methodClinical characteristics of the treated patients

Tumor stageTumor stage      

Stage IIIStage III 00 00

Stage IVStage IV 88 88

Extend of disease(nr.)Extend of disease(nr.)      

With local metastasesWith local metastases 3 (8)3 (8) 3 (8)3 (8)

With distant metastasesWith distant metastases 7(8)7(8) 7 ( 8)7 ( 8)

Previous therapyPrevious therapy      

Surgical orchiectomySurgical orchiectomy 6 (8)6 (8) 5 (8)5 (8)

AntiandrogensAntiandrogens 8 (8)8 (8) 7 (8)7 (8)

Palliative radiotherapyPalliative radiotherapy 4 (8)4 (8) 00

PSA(ng/ml)PSA(ng/ml)      

MedianMedian 389,6389,6 1511,21511,2

RangeRange 63,3-132063,3-1320 17,16- 839517,16- 8395

Al. phosphatase mg/mlAl. phosphatase mg/ml      

MedianMedian 16731673 11201120

RangeRange 246-4286246-4286 253-5264253-5264

Patients and methodPatients and method

Pre-treatment evaluation of the Pre-treatment evaluation of the patients patients

Control lab examsControl lab exams Objective responseObjective response Quality of lifeQuality of life

Patients and method Patients and method

Self Compilation Questionnaire for Determination of Subjective Status according to G.Beretta

TreatmentTreatment

Insulin potentiation therapy (IPT)Insulin potentiation therapy (IPT)::1.Group A1.Group A - Insulin i.v. ( 0,4 UI/kg.) in - Insulin i.v. ( 0,4 UI/kg.) in

combination with Cyclophosphamide (0,10-0,15 combination with Cyclophosphamide (0,10-0,15 g /m2 ) / Epirubicine (3 mg /m2 ); Vinblastine g /m2 ) / Epirubicine (3 mg /m2 ); Vinblastine (0,5mg /m2 ) i.v. in 8 patients(0,5mg /m2 ) i.v. in 8 patients;;

2.Group B2.Group B – – Insulin i.v. (0,4 UI/kg. ) in Insulin i.v. (0,4 UI/kg. ) in combination with Docetaxel (3,6 mg /m2) i.v. in 8 combination with Docetaxel (3,6 mg /m2) i.v. in 8 patients.patients.

Length one scan treatment – 6 applications in every Length one scan treatment – 6 applications in every 5 days interval, then sustaining treatment in 5 days interval, then sustaining treatment in gradual increasing intervals (four applications in 10 gradual increasing intervals (four applications in 10 days, 2, 3 and more weeks). days, 2, 3 and more weeks).

In the interval:In the interval: Dexamethason Dexamethason – 20 – 20 mgmg., ., Cyclophosphamide Cyclophosphamide - 50 - 50 mgmg. . pp..oo., ., DoxycyclinDoxycyclin-100 -100 mgmg, , LegalonLegalon 3 3 x x 140 140 mgmg., ., Celebrex 2 xCelebrex 2 x 7,5 7,5 mgmg., ., antioxidants and ozone therapy antioxidants and ozone therapy ..

Maintaining treatment consists of no more Maintaining treatment consists of no more than 24 IPT applications.than 24 IPT applications.

Treatment resultsTreatment results

Treatment results (after 6 IPT)

   Group AGroup A Group BGroup B OverallOverall

   nn nn n(%)n(%)

Complete Complete responsrespons 00 00 00

Partial responsPartial respons 5 (8)5 (8) 3 (8) 3 (8) 8 /16 (50)8 /16 (50)

Stabile diseaseStabile disease 2 (8)2 (8) 2 (8)2 (8) 4 /16 (25)4 /16 (25)

Progressive Progressive diseasedisease 1 (8)1 (8) 3 (8)3 (8) 4 /16 (25)4 /16 (25)

Treatment results Treatment results

Treatment results (after 10 IPT)

   Group AGroup A Group BGroup B OverallOverall

   nn nn n(%)n(%)

Complete Complete responsrespons 1 (5)1 (5) 2 (4)2 (4) 3/9 (33)3/9 (33)

Partial responsPartial respons 0 (5)0 (5) 1 (4)1 (4) 1/9 (11)1/9 (11)

Stabile diseaseStabile disease 2 (5)2 (5) 0 (4)0 (4) 2/9 (22)2/9 (22)

Progressive Progressive diseasedisease 2 (5)2 (5) 1 (4)1 (4) 3/9 (33)3/9 (33)

Treatment resultsTreatment results

The mean values of PSAThe mean values of PSA

Group AGroup A Before treatment After 6th (course of treatment) Before treatment After 6th (course of treatment)

IPT After the 10th courseIPT After the 10th course256, 7 ng/ml 94,6 ng/ml. 256, 7 ng/ml 94,6 ng/ml.

36,3 ng/ml. 36,3 ng/ml.

Group BGroup BBefore treatment After 6th (course of treatment) Before treatment After 6th (course of treatment)

IPT After the 10th courseIPT After the 10th course2215,3 ng/ml 956,2 ng/ml 2215,3 ng/ml 956,2 ng/ml

4,9 ng/ml 4,9 ng/ml

Treatment results - Subjective Treatment results - Subjective improvementimprovement

23,7

8,1

28

15

0 00

5

10

15

20

25

30

Subjectiveimprovement

>50%

Subjectiveimprovement

<50%

Treatmentfailure

Beretta Mean values for group A

bifore treatment

after treatment

Quality of life assessment according to Berreta Symptoms Index, after the 6th IPТ course for Group А

Treatment results - Subjective Treatment results - Subjective improvementimprovement

23,7

8,3

24,420,4

0 0

0

5

10

15

20

25

Subjectiveimprovement

>50%

Subjectiveimprovement

<50%

Treatmentfailure

Beretta mean values for group B

bifore treatment

after treatment

Quality of life assessment according to Berreta Symptoms Index, after the 6th IPТ course for Group B

DiscussionDiscussion

The theoretical conception for the The theoretical conception for the mechanisms of action of IPTmechanisms of action of IPT

Problems of the treatment of hormone-Problems of the treatment of hormone-resistant prostate tumors.resistant prostate tumors.

In search of a new method for lowering the In search of a new method for lowering the toxicity of the chemotherapy for treating toxicity of the chemotherapy for treating oncological diseases we began in 2006 to oncological diseases we began in 2006 to implement IPTLD combined with LHRH implement IPTLD combined with LHRH agonist Gosrelin depot 3,6 mg.agonist Gosrelin depot 3,6 mg.

Despite the advanced stage of disease in Despite the advanced stage of disease in patients treated by uspatients treated by us the treatment is well the treatment is well tolerated wittolerated without any serious side effects. hout any serious side effects.

Quality of life after the second Quality of life after the second IPTLD IPTLD application is significantly improved, and application is significantly improved, and this applies even to patients with treatment this applies even to patients with treatment failure in terms of PSA criteria.failure in terms of PSA criteria.

ConclusionConclusion

Our present experience with IPTLD (in more Our present experience with IPTLD (in more than 400 treated patients) with various than 400 treated patients) with various tumors, as well as the practical experience tumors, as well as the practical experience of the growing number of doctors practicing of the growing number of doctors practicing the method gives us a reason to assume the method gives us a reason to assume that IPTLD method provides a real that IPTLD method provides a real opportunity for resolving one of the most opportunity for resolving one of the most serious problems of toxicity associated with serious problems of toxicity associated with chemotherapy using maximum tolerated chemotherapy using maximum tolerated doses. doses.

A certain advantage of the method along A certain advantage of the method along with its effectiveness is the significantly with its effectiveness is the significantly improved quality of life of the treated improved quality of life of the treated patients. patients.

In spite of the small number of patients In spite of the small number of patients treated by us with castrate resistant treated by us with castrate resistant prostate tumor, the preliminary results are prostate tumor, the preliminary results are promising and this gives us hope and promising and this gives us hope and expectations for future serious researches expectations for future serious researches on the potential of widespread clinical use on the potential of widespread clinical use of IPTLD.of IPTLD.

Thank you for your attention !Thank you for your attention !