Optimizarea unui protocol de chimioterapie in cancerul bronho-pulmonar cu ajutorul algoritmilor evolutivi

Introducere Cancer = Boala care are ca mecanism o proliferare celulara anarhica, necontrolata si neintrerupta. Dac celulele canceroase se nmulesc n plmn, excrescena format se numete tumor pulmonar primar.

Clasificarea cancerelelor bronho pulmonare cancerele bronho-pulmonare non-microcelulare (non small-cell, CBPNS) cancerele microcelulare (small cell, CBPSC) 75-80%

20-25%

Principii de tratament Chirurgia - vindecarea ar fi posibil numai printr-o rezecie chirurgical complet (posibil 15-20%)Radioterapia - tratament standard pentru CBP inoperabile Chimioterapia - tratamentul cu medicamente numite citostatice care distrug celulele tumorale.

Protocoale de chimioterapie:

ProtocolDozeRata de raspunsObs.Cisplatin+ Vinorelbine80 120 mg/m i.v. la 4-6 sapt.30mg/m/sapt 35-51%Se repeta in ziua 29Carboplatin + Etoposide300-375mg/m x1100-130mg/m x310-30%Se repeta in ziua 29

Paclitaxel + Cisplatin135 mg/m2 ziua 1 (perfuzie continu 24h) 75 mg/m2 i.v. ziua 127 32%Se repet la fiecare 21 de zile

Protocolul CE:Carboplatin este un complex organic de metale grele continand in centru un atom de platina; produce legaturi intre si in interiorul lanturilor ADN, modificand structura si inhiband astfel sinteza acestuia. Etoposida este un derivat semisintetic de podofilotoxina; inhiba intrarea in mitoza (profaza) a celulelor tumorale, prin actiunea de complexare a topoizomerazei II.

Ecuatiile lui Martin: dx1 = - x1+ k(x2 - )H(x2 - ) dt

dx2 = u - x2 dt dx3 = x2 dt

unde:x1-este invers proportionala cu masa tumoarei

x2-este concentratia de medicament in organism in unitati de medicament

x3-este toxicitatea medicamentului cumulat in organism

(per zi) = 0,00099k (per zi per D)= 0,00840 (D)= 10 (per zi)= 0,27u = 2,56721 = 0,4

Rezolvarea Sistemului de 3 ecuatii diferentiale reprezinta de fapt simularea Modelului lui Martin (fara constrangeri) cu parametrii stabiliti conventional pt acest studiu.Atfel se obtin valori ale masei tumorale care nu corespund in totalitate cu experientele clinice

Modelul lui Martin fara cele 3 constrangeri - Etoposide

Chart1

Chart1

Sheet2

Dayx1x2x3

04.60168.000.00

15.76130.50121.21

26.64101.87175.64

37.3180.02191.65

47.8163.33186.75

58.2050.60171.54

68.4940.88152.23

78.7133.45132.33

88.8727.79113.67

98.9923.4697.12

109.0820.1682.93

119.1517.6471.05

129.1915.7261.28

139.2314.2553.36

149.2513.1347.00

159.2612.2741.93

169.2711.6237.92

179.2711.1234.76

189.2710.7432.29

199.2610.4530.36

209.2610.2228.86

219.2510.0527.70

229.249.9326.79

239.239.8326.09

249.229.7525.56

259.219.6925.14

269.209.6524.82

279.199.6224.58

289.199.5924.39

299.18168.0024.24

3010.33130.50137.46

3111.21101.87186.53

3211.8780.02198.96

3312.3763.33191.65

3412.7550.60174.82

3513.0440.88154.43

3613.2533.45133.80

3713.4127.79114.66

3813.5323.4697.78

3913.6120.1683.37

4013.6717.6471.35

4113.7215.7261.48

4213.7414.2553.49

4313.7613.1347.09

4413.7712.2741.99

4513.7711.6237.96

4613.7711.1234.79

4713.7610.7432.31

4813.7610.4530.37

4913.7410.2228.87

5013.7310.0527.70

5113.729.9326.80

5213.719.8326.10

5313.699.7525.56

5413.689.6925.14

5513.669.6524.82

5613.659.6224.58

5713.649.5924.39

5813.62168.0024.24

5914.77130.50137.46

6015.64101.87186.53

6116.3080.02198.96

6216.8063.33191.65

6317.1850.60174.82

6417.4640.88154.43

6517.6733.45133.80

6617.8227.79114.66

6717.9423.4697.78

6818.0220.1683.37

6918.0717.6471.35

7018.1115.7261.48

7118.1314.2553.49

7218.1513.1347.09

7318.1512.2741.99

7418.1511.6237.96

7518.1411.1234.79

7618.1310.7432.31

7718.1210.4530.37

7818.1010.2228.87

7918.0910.0527.70

8018.079.9326.80

8118.059.8326.10

8218.039.7525.56

8318.029.6925.14

8418.009.6524.82

Sheet2

Sheet3

Modelul lui Martin cu constrangeri - Etoposide

Chart1

Chart1

Sheet1

x1x2x3

04.60168.000.00

15.84130.50121.21

26.80101.87175.64

37.5580.02191.65

48.1463.33186.75

58.6150.60171.54

68.9840.88152.23

79.2833.45132.33

89.5227.79113.67

99.7223.4697.12

109.8920.1682.93

1110.0417.6471.05

1210.1715.7261.28

1310.2814.2553.36

1410.3813.1347.00

1510.4812.2741.93

1610.5611.6237.92

1710.6511.1234.76

1810.7310.7432.29

1910.8010.4530.36

2010.8810.2228.86

2110.9510.0527.70

2211.029.9326.79

2311.099.8326.09

2411.169.7525.56

2511.239.6925.14

2611.299.6524.82

2711.369.6224.58

2811.439.5924.39

2911.50168.0024.24

3012.73130.50137.46

3113.68101.87186.53

3214.4380.02198.96

3315.0163.33191.65

3415.4750.60174.82

3515.8340.88154.43

3616.1233.45133.80

3716.3627.79114.66

3816.5623.4697.78

3916.7220.1683.37

4016.8617.6471.35

4116.9815.7261.48

4217.0914.2553.49

4317.1813.1347.09

4417.2712.2741.99

4517.3511.6237.96

4617.4311.1234.79

4717.5010.7432.31

4817.5710.4530.37

4917.6410.2228.87

5017.7010.0527.70

5117.779.9326.80

5217.839.8326.10

5317.899.7525.56

5417.959.6925.14

5518.019.6524.82

5618.079.6224.58

5718.149.5924.39

5818.20168.0024.24

5919.42130.50137.46

6020.37101.87186.53

6121.1180.02198.96

6221.6863.33191.65

6322.1350.60174.82

6422.4940.88154.43

6522.7833.45133.80

6623.0127.79114.66

6723.2023.4697.78

6823.3620.1683.37

6923.4917.6471.35

7023.6015.7261.48

7123.7014.2553.49

7223.7913.1347.09

7323.8712.2741.99

7423.9511.6237.96

7524.0211.1234.79

7624.0810.7432.31

7724.1410.4530.37

7824.2010.2228.87

7924.2610.0527.70

8024.329.9326.80

8124.389.8326.10

8224.439.7525.56

8324.499.6925.14

8424.549.6524.82

Sheet1

Sheet2

Sheet3

Modelul lui Martin fara cele 3 constrangeri -Carboplatina

Chart1

Chart1

Sheet1

x1x2x3

04.60343.000.00

17.04264.09246.39

28.91203.86355.12

310.32157.87384.93

411.40122.77372.02

512.2295.97338.25

612.8475.51296.44

713.3159.89253.78

813.6647.97214.01

913.9338.87178.82

1014.1231.92148.72

1114.2726.62123.57

1214.3822.57102.92

1314.4619.4886.18

1414.5117.1272.74

1514.5515.3262.05

1614.5713.9453.59

1714.5912.8946.93

1814.5912.0941.72

1914.5911.4837.65

2014.5911.0134.49

2114.5810.6632.03

2214.5710.3930.13

2314.5610.1828.66

2414.5510.0227.53

2514.539.9026.66

2614.529.8125.99

2714.509.7425.47

2814.499.6825.07

2914.48343.0024.77

3016.91264.09262.99

3118.76203.86366.25

3220.17157.87392.39

3321.24122.77377.02

3422.0595.97341.60

3522.6675.51298.69

3623.1159.89255.29

3723.4647.97215.02

3823.7138.87179.50

3923.9031.92149.18

4024.0426.62123.88

4124.1422.57103.12

4224.2119.4886.31

4324.2517.1272.83

4424.2815.3262.11

4524.2913.9453.63

4624.3012.8946.96

4724.2912.0941.74

4824.2911.4837.67

4924.2711.0134.50

5024.2510.6632.04

5124.2410.3930.14

5224.2110.1828.67

5324.1910.0227.53

5424.179.9026.66

5524.149.8125.99

5624.129.7425.47

5724.099.6825.07

5824.07343.0024.77

5926.50264.09262.99

6028.34203.86366.25

6129.74157.87392.39

6230.80122.77377.02

6331.5995.97341.60

6432.1975.51298.69

6532.6459.89255.29

6632.9847.97215.02

6733.2238.87179.50

6833.4031.92149.18

6933.5326.62123.88

7033.6222.57103.12

7133.6819.4886.31

7233.7117.1272.83

7333.7315.3262.11

7433.7413.9453.63

7533.7312.8946.96

7633.7212.0941.74

7733.7011.4837.67

7833.6811.0134.50

7933.6510.6632.04

8033.6210.3930.14

8133.5910.1828.67

8233.5610.0227.53

8333.539.9026.66

8433.499.8125.99

Sheet1

Sheet2

Sheet3

Modelul lui Martin cu constrangeri -Carboplatina

Chart1

Chart1

Sheet1

x1x1x3

04.60343.000.00

17.13264.09246.39

29.07203.86355.12

310.57157.87384.93

411.73122.77372.02

512.6395.97338.25

613.3375.51296.44

713.8859.89253.78

814.3147.97214.01

914.6638.87178.82

1014.9431.92148.72

1115.1726.62123.57

1215.3522.57102.92

1315.5119.4886.18

1415.6517.1272.74

1515.7715.3262.05

1615.8713.9453.59

1715.9712.8946.93

1816.0512.0941.72

1916.1311.4837.65

2016.2111.0134.49

2116.2810.6632.03

2216.3510.3930.13

2316.4210.1828.66

2416.4910.0227.53

2516.559.9026.66

2616.619.8125.99

2716.689.7425.47

2816.749.6825.07

2916.80343.0024.77

3019.32264.09262.99

3121.25203.86366.25

3222.74157.87392.39

3323.88122.77377.02

3424.7795.97341.60

3525.4675.51298.69

3626.0059.89255.29

3726.4247.97215.02

3826.7538.87179.50

3927.0231.92149.18

4027.2426.62123.88

4127.4122.57103.12

4227.5619.4886.31

4327.6817.1272.83

4427.7915.3262.11

4527.8813.9453.63

4627.9612.8946.96

4728.0412.0941.74

4828.1111.4837.67

4928.1711.0134.50

5028.2310.6632.04

5128.2910.3930.14

5228.3510.1828.67

5328.4010.0227.53

5428.469.9026.66

5528.519.8125.99

5628.569.7425.47

5728.619.6825.07

5828.66343.0024.77

5931.16264.09262.99

6033.08203.86366.25

6134.56157.87392.39

6235.69122.77377.02

6336.5795.97341.60

6437.2575.51298.69

6537.7759.89255.29

6638.1847.97215.02

6738.5138.87179.50

6838.7631.92149.18

6938.9726.62123.88

7039.1322.57103.12

7139.2719.4886.31

7239.3817.1272.83

7339.4715.3262.11

7439.5513.9453.63

7539.6212.8946.96

7639.6912.0941.74

7739.7411.4837.67

7839.8011.0134.50

7939.8510.6632.04

8039.8910.3930.14

8139.9410.1828.67

8239.9810.0227.53

8340.029.9026.66

8440.069.8125.99

Sheet1

Sheet2

Sheet3

Concluzii:Pentru a omori un numar maxim de celule ale tumorii cu un minimum de toxicitate in prima zi, corpul pacientului are cele mai puternice capacitati metabolice si totodata rezistenta celulelor tumorii este cea mai slaba, deci prin administrarea unei supradozese obtine eficienta cea mai buna.

Concluzii:Cele 3 constrangeri nu pot imbunatati lupta impotriva cancerului, dar reduce efectul toxic al chimioterapiei, au rolul de a obtine eficiente maxime in programele medicamentoase.