Lokal ilerlemiş rektal karsinomalı hastalarda preoperatif radyoterapi ile birlikte verilen önerilmiş dozdaki raltitrexed'in tedaviye cevabı

Yıl 2009, Cilt: 24 Sayı: 3, 99 - 107, 01.04.2009

Tayfun Hancılar Levent Işıklı Yakup Büyükpolat Halil Akboru Tanju Berber Mustafa Ünsal

Öz

OBJECTIVES We aimed to evaluate the treatment response and toxic effects of the recommended dose of raltitrexed when delivered concurrently with preoperative radiotherapy in patients with locally advanced rectal carcinoma. METHODS This open-labeled, prospective and non-comparative study was conducted with 49 patients. Radiotherapy (50.4 Gy) was delivered in 1.8 Gy daily fractions five times per week for 5-6 weeks. Single doses of 2.6 mg/m2 raltitrexed were infused over 15 minutes 1 hour prior to radiotherapy on days 1 and 22. Treatment response and toxicity were clinically assessed by hematological and biochemical tests and World Health Organization performance status scoring. RESULTS Overall treatment response was 42.9%. Post-treatment resectability opportunity was achieved in 67.3% patients. Raltitrexed was found to be related to 52.6% of the total adverse events. CONCLUSION The combination of raltitrexed and radiotherapy appears promising as neoadjuvant therapy in patients with inoperable rectal cancer with higher but manageable gastrointestinal toxicity.

Anahtar Kelimeler

-

Lokal ilerlemiş rektal karsinomalı hastalarda preoperatif radyoterapi ile birlikte verilen önerilmiş dozdaki raltitrexed'in tedaviye cevabı

Öz

AMAÇ Bu çalışmada, lokal ilerlemiş rektal karsinomalı hastalarda preoperatif radyoterapi ile birlikte verilen önerilmiş dozdaki raltitrexed'in tedaviye cevabı ve toksik etkileri değerlendirildi. GEREÇ VE YÖNTEM Bu açık-etiketli, prospektif ve karşılaştırmalı olmayan çalışma 49 hasta üzerinde yürütüldü. 50.4 Gy radyoterapi 5-6 hafta süreyle haftada 5 kere 1.8 Gy'lik fraksiyone dozlar şeklinde verildi. Tek doz şeklinde 2.6 mg/m2 raltitrexed 1. ve 22. günlerde radyoterapiden 1 saat once 15 dakika süreyle infüze edildi. Tedaviye cevap ve toksisite klinik olarak hematolojik ve biyokimyasal testler ve Dünya Sağlık Örgütü performans skoru ile değerlendirildi. BULGULAR Tüm tedavi cevabı %42.9 idi. Tedavi sonrası rezektabilite oranı hastaların %67.3'ünde görüldü. Toplam advers olayların %52.6'sı raltitrexed'e bağlı bulundu. SONUÇ İnoperabl rektal kanserli hastalarda raltitrexed-radyoterapi birleşimi yüksek oranda ancak tedavi edilebilir gastrointestinal toksisite ile birlikte ümit verici bir neoadjuvan tedavi olarak gözükmektedir.

Anahtar Kelimeler

Rektal kanser, raltitrexed, radyoterapi, yaşam süresi, toksisite

Kaynakça

• 1. André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004;350(23):2343-51.
• 2. International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators. Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. Lancet 1995;345(8955):939-44.
• 3. Glimelius B, Hoffman K, Olafsdottir M, Påhlman L, Sjödén PO, Wennberg A. Quality of life during cytostatic therapy for advanced symptomatic colorectal carcinoma: a randomized comparison of two regimens. Eur J Cancer Clin Oncol 1989;25(5):829-35.
• 4. Scheithauer W, Rosen H, Kornek GV, Sebesta C, Depisch D. Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. BMJ 1993;306(6880):752-5.
• 5. Valentini V, Doglietto GB, Morganti AG, Turriziani A, Smaniotto D, De Santis M, et al. Preoperative chemoradiation with raltitrexed (Tomudex) for T2/N+ and T3/N+ rectal cancers: a phase I study. Eur J Cancer 2001;37(16):2050-5.
• 6. Scheithauer W, Rosen H, Kornek GV, Sebesta C, Depisch D. Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. BMJ 1993;306(6880):752-5.
• 7. Thomas RJ, Williams M, Garcia-Vargas J. Lessons learned from raltitrexed--quality assurance, patient education and intensive supportive drugs to optimise tolerability. Clin Oncol (R Coll Radiol) 2003;15(5):227-32.
• 8. Chari RS, Tyler DS, Anscher MS, Russell L, Clary BM, Hathorn J, et al. Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum. Ann Surg 1995;221(6):778-86.
• 9. Grann A, Minsky BD, Cohen AM, Saltz L, Guillem JG, Paty PB, et al. Preliminary results of preoperative 5-fluorouracil, low-dose leucovorin and concurrent radiation therapy for clinically resectable T3 rectal cancer. Dis Colon Rectum 1997;40(5):515-22.
• 10. Rich TA, Skibber JM, Ajani JA, Buchholz DJ, Cleary KR, Dubrow RA, et al. Preoperative infusional chemoradiation therapy for stage T3 rectal cancer. Int J Radiat Oncol Biol Phys 1995;32(4):1025-9.
• 11. Valentini V, Coco C, Cellini N, Picciocchi A, Genovesi D, Mantini G, et al. Preoperative chemoradiation for extraperitoneal T3 rectal cancer: acute toxicity, tumor response and sphincter preservation. Int J Radiat Oncol Biol Phys 1998;40(5):1067-75.
• 12. Valentini V, Coco C, Cellini N, Picciocchi A, Rosetto ME, Mantini G, et al. Preoperative chemoradiation with cisplatin and 5-fluorouracil for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, sphincter preservation. Int J Radiat Oncol Biol Phys 1999;45(5):1175-84.
• 13. Di Bartolomeo M, Bajetta E, Buzzoni R, Bozzetti F, Artale S, Valvo F. Integrated treatment with doxifluridine and radiotherapy in recurrent or primary unresectable rectal cancer. A feasibility study. Tumori 1999; 85(3):211-3.
• 14. Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004; 351(17):1731-40.
• 15.Jackman AL, Taylor GA, Gibson W, Kimbell R, Brown M, Calvert AH, et al. ICI D1694, a quinazoline antifolate thymidylate synthase inhibitor that is a potent inhibitor of L1210 tumor cell growth in vitro and in vivo: a new agent for clinical study. Cancer Res 1991; 51(20):5579-86.
• 16. Cunningham D. Mature results from three large controlled studies with raltitrexed (‘Tomudex’). Br J Cancer 1998;77 Suppl 2:15-21.
• 17. Cocconi G, Cunningham D, Van Cutsem E, Francois E, Gustavsson B, van Hazel G, et al. Open, randomized, multicenter trial of raltitrexed versus fluorouracil plus high-dose leucovorin in patients with advanced colorectal cancer. Tomudex Colorectal Cancer Study Group. J Clin Oncol 1998;16(9):2943-52.
• 18. Zalcberg JR, Cunningham D, Van Cutsem E, Francois E, Schornagel J, Adenis A, et al. ZD1694: A novel thymidylate synthase inhibitor with substantial activity in the treatment of patients with advanced colorectal cancer. ‘Tomudex’ International Study Group. Clin Oncol 1996;14(3):716-21.
• 19. Michels J, Geldart T, Darby A, Craddock L, Iveson A, Richardson L, et al. The combination of raltitrexed (Tomudex) and mitomycin-C in the treatment of advanced colorectal cancer: a phase II study. Clin Oncol (R Coll Radiol) 2006;18(6):431-5.
• 20. Cunningham D, Zalcberg J, Maroun J, James R, Clarke S, Maughan TS, et al. Efficacy, tolerability and management of Raltitrexed (Tomudex) monotherapy in patients with advanced colorectal cancer. A review of phase II/III trials. Eur J Cancer 2002;38(4):478-86.
• 21.James R, Price P, Valentini V. Raltitrexed (Tomudex) concomitant with radiotherapy as adjuvant treatment for patients with rectal cancer: preliminary results of phase I studies. 1999;35 Supduring treatment with raltitrexed (Tomudex) in 861 patients: implications for patient management. Eur J Cancer 1999;35(Suppl 4):72.
• 23. Lupattelli M, Maranzano E, Bellavita R, Natalini G, Corgna E, Rossetti R, et al. Raltitrexed and radiotherapy as adjuvant treatment for stage II-III rectal cancer: a feasibility study. Tumori 2005;91(6):498-504.
• 24. Maughan TS, James RD, Kerr DJ, Ledermann JA, McArdle C, Seymour MT, et al. Comparison of survival, palliation, and quality of life with three chemotherapy regimens in metastatic colorectal cancer: a multicentre randomised trial. Lancet 2002;359(9317):1555-63.
• 25. Drug-company decision to end cancer trial. Lancet 1999;354(9184):1045.
• 26. Cao S, Bhattacharya A, Durrani FA, Fakih M. Irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer. Expert Opin Pharmacother 2006;7(6):687-703.