1. Treatment Cost of Metastatic Colon CA in Turkey Kockaya, Guvenc (1); Polat, Mine (2); Özet, Ahmet (3); Vural, İsmail Mert (1); Akbulat, Akif (1); Akar, Halil (1); Kerman, Saim (1) guvenckockaya@yahoo.com 1: General Directorate of Pharmaceuticals and Pharmacy, Turkey; 2: Baskent University, Turkey; 3: Gazi University, Turkey

2. Abstract Problem statement: Colon cancer is the third most common in the top cancer incidence list—212,000 patients die in Europe per year because of colon cancer. In Turkey 150,000-180,000 new cancer patients are diagnosed every year, 13% of whom have colon cancer. Metastasis will occur among 50% of the patients who are newly diagnosed and operated on. It is believed that metastasis will occur in 9,000-10,000 colon cancer patients every year in Turkey. Objective: Survival appears to be prolonged to more than 20 months with the new pharmaceuticals; however, these new pharmacuticals increase the total cost. The aim of our study is to calculate colon cancer treatment options for Turkey.

3. Abstract Method: Gazi University Hospital treatment protocols for colon cancer treatment were used. The cost of Irinotekan-Erbutix, B-IFL, Bevacizumab-FUFA, XELOX, XELIRI, IFL-Cetuximab, Irinotekan, FOLFIRI-Doillard, FOLFOX-4, FOLFIRI-Tornigard, Raltrexed, FUFA, and Inf-5 FU (Degramount) protocols were calculated. The cost of pharmaceuticals and medical treatment used in the protocols were taken from the Social Security Institution’s website. The exchange rate was USD 1 for TL 1.5. Results: Inf-5 FU (Degramount) (USD 220) had the lowest cost for 1 cycle, followed by FUFA (USD 342), FOLFIRI-Tornigard (USD 390), Raltrexed (USD 504), FOLFIRI-Doillard (USD 521), Irinotekan (USD 619), FOLFOX-4 (USD 704), XELOX (USD 880), XELIRI (USD 947), IFL (USD 1785), Bevacizumab-FUFA (USD 2730), B-IFL (USD 5203), and Irinotekan- Cetixumab (USD 11625).

4. Abstract Conclusion: Every treatment protocol is administered for 6 cycles for each patient depending on the disease’s stage. If a treatment protocol is not successful, the patient will be given a different protocol. Different combinations of cycles can be administered, depending on the responses of the patients. Although Irinotekan- Cetixumab had the highest cycle cost, further analysis is needed to compare the cost and effectiveness of different protocols and combinations. Funding source: There was not any funding source or conflicyt of interest for the manuscript

5. Introduction & Objectives Generally, colon and rectum cancers are referred as colorectal cancer (CRC). Colorectal cancer develops slowly in years. In Turkey, incidance of cancer is 173,85 in per 100.000, 7,1 % of whom are diagnosed to have developed colon cancer. In addition to prevelance and great mortality numbers metastases will develop in 30– 40% of CRC patients. This metastase rate can cause mortality also. In the light of these, it could be said that metastase will occur in 2-3.000 colon cancer patients every year in Turkey. Cost of treatment of CRC is high also. The aim of our study is to calculate the cost of colon cancer treatment protocols and cost of per year with different combinations of protocols for Turkey.

6. Methods Gazi University Hospital treatment protocols for colon cancer treatment were used. The cost of Irinotekan-Erbutix, B-IFL, Bevacizumab- FUFA, XELOX, XELIRI, IFL-Cetuximab, Irinotekan, FOLFIRI-Doillard, FOLFOX-4, FOLFIRI-Tornigard, Raltrexed, FUFA, and Inf-5 FU (Degramount) protocols were calculated. The cost of pharmaceuticals and medical treatment used in the protocols were taken from the Social Security Institution’s website. The exchange rate was USD 1 for TL 1.5.

7. Cost of Pharmaceuticals MoleculesPackage Average Price (in $ USD) 5-Fluorourasil500 mg2,93 (2,71-3,12) 1000 mg5,50 (5,34-5,82) Bevacizumab100 mg307,12 400 mg1140,55 Cetuximab100 mg276 500 mg1533,33 Folinik asit40 mg0,67 (0,56-0,76) Irinotekan40 mg58,36 100 mg135,66 Kapesitabin150 mg 60 tbl59,21 500 mg 60 tbl344,57 Oxaliplatin50 mg 108,28 (105,99- 111,61) 100 mg 215,31 (210,8- 242,41) Raltireksed2 mg142,30

8. Protocols Table 1: Protocols ProtocolPharmaceuticalAdministration1.D2.D3.D4.D5.D14.D FUFA (5FU/LV) (1 amp Metpamid, 1 amp Decort, 1 amp Systal and laboratories) 5-Fluorourasil (425 mg/m 2 ) 15 mn. İnfusion in 250 cc SF +++++ Folinik asit (20 mg/m 2 ) i.v. push+++++ FOLFIRI (tropisetron 5 mg or ondansetron 4-8 mg, 1 amp Decort + 1 amp Systral and laboratories) Irinotekan (180 mg/m 2 ) 90 mn. infusion in 250cc SF + Folinik asit (200 mg/m 2 ) 2 hrs infusion in 250 cc SF ++ 5-FU (400 mg/m 2 ) 15 mn. in 250cc SF ++ 5-FU (600 mg/m 2 ) 22 hrs infusion in 1000 cc SF ++ FOLFOX (tropisetron 5 mg or ondansetron 4-8 mg, 1 amp Dekort, 1 amp Systral) Oxaliplatin (85 mg/m 2 ) 2 hrs infusion in 1000 cc %5 dextroz + Folinik asit (200 mg/m 2 ) 2 hrs infusion in 250 cc %5 dextroz ++ 5-FU (400 mg/m 2 ) 15 mn. infusion in 250 cc SF ++ 5-FU (600 mg/m 2 ) 22 hrs. İnfusion in 1000 cc SF ++ Bevacizumab/FUFA (1 amp Metpamid, 1 amp Dekort and 1 amp Systral) Bevacizumab (5 mg/kg) in 100 cc SF++ 5-Fluorourasil (425 mg/m 2 ) 15 mn. infusion in 250 cc SF +++++ Folinik asit (20 mg/m 2 ) i.v. push+++++

9. Protocols ProtocolPharmaceutical Administratio n 1.D8.D15.D22.D29.D Bevacizumab/FOLFIRI (tropisetron 5 mg or ondansetron 4-8 mg, 1 amp Decort + 1 amp Systral and laboratories) Irinotekan (125 mg/m 2 ) 90 mn. infusion in 250 cc SF ++++ Folinik asit (20 mg/m 2 ) i.v. push++++ 5-FU (500 mg/m 2 ) 15 mn infusion in 250 cc SF ++++ Bevacizumab (5 mg/kg) in 100 cc SF+++ Bevacizumab/FOLFOX (tropisetron 5 mg or ondansetron 4-8 mg, 1 amp Dekort, 1 amp Systral) Bevacizumab (5 mg/kg) in 100 cc SF++ Oxaliplatin (85 mg/m 2 ) 2 hrs infusion in 1000 cc %5 dextroz + Folinik asit (200 mg/m 2 ) 2 hrs infusion in 250 cc %5 dextroz ++ 5-FU (400 mg/m 2 ) 15 mn. infusion in 250 cc SF ++ 5-FU (600 mg/m 2 ) 22 hrs. İnfusion in 1000 cc SF ++ Irinotekan (tropisetron 5 mg or ondansetron 4-8 mg, 1 amp Dekort, 1 amp Systral) (350 mg/m 2 ) 90 mn infusion in 250 cc SF + İrinotekan +Cetuximab (tropisetron 5 mg or ondansetron 4-8 mg, 1 amp Dekort, 1 amp Systral) İrinotekan (200mg) 90 mn infusion in 250 cc SF ++ Cetuximab (begining 700 mg, maintenance 500 mg) 120 mn iv infusion +++ Raltireksed (tropisetron 5 mg or ondansetron 4-8 mg, 1 amp Dekort, 1 amp Systral) Raltireksed (3 mg/m 2 ) 15 mn infusion 250 cc SF + Xeliri (tropisetron 5 mg or ondansetron 4-8 mg, 1 amp Dekort, 1 amp Systral) Irinotekan (250 mg/m 2 ) 90 mn infusion in 250 cc SF + Kapesitabin (1500 mg/m 2 /day) 2 dose in a day++ Xelox (tropisetron 5 mg or ondansetron 4-8 mg, 1 amp Dekort, 1 amp Systral) Oxaliplatin (130 mg/m 2 ) 2 hrs infusion in 250 cc %5 dextroz + Kapesitabin (1500 mg/m 2 /gün) 2 dose in a day++

10. Results The lowest cost for one cycle was established by FUFA (US $ 342). It were followed by FOLFIRI (US$ 390), Raltireksed (US$ 512), Irinotekan (US$ 619), FOLFOX (US$ 704), Bevacizumab/FUFA (US$ 2730), Xelox (US$ 3685), Xeliri (US$ 3774), Bevacizumab/FOLFOX (US$ 4367), Bevacizumab/FOLFIRI (US$ 5203) and Irinotekan/Cetixumab (US$ 11625).

11. Cost of Protocols ProtocolsCost (in US$) FolfiriUS$ 390 RaltireksedUS$ 512 IrinotekanUS$ 619 FOLFOXUS$ 704 Bevacizumab/FUFA US$ 2730 XeloxUS$ 3685 XeliriUS$ 3774 Bevacizumab/FOLFO X US$ 4367 Bevacizumab/FOLFI RI US$ 5203 Irinotekan/CetixumabUS$ 11625

12. Conclusion Every treatment protocol is administered for 6 cycles for each patient depending on the disease’s stage. If a treatment protocol is not successful, the patient will be given a different protocol. Different combinations of cycles can be administered, depending on the responses of the patients. Although Irinotekan-Cetixumab had the highest cycle cost, further analysis is needed to compare the cost and effectiveness of different protocols and combinations.