Gemcitabine and carboplatin combination in patients with advanced and locally advanced stage non-small cell lung cancer

Abstract

OBJECTIVES The aim was to evaluate the efficacy, toxicity and survival results of gemcitabine and carboplatin (GCa) combination in patients with advanced and locally advanced non-small cell lung cancer (NSCLC). METHODS Forty-one patients (40 males, 1 female; mean age 59; range 43 to 72 years) diagnosed histopathologically, with good performance and without previous chemotherapy were included in the study. RESULTS Complete response (CR) was observed in 2.4% and partial response (PR) in 34.1%. CR and PR were found in 4.2% and 41.7% in stage IIIB, and in 0% and 23.5% in stage IV. The mean survival and one-year survival rates were 14 months and 54.2% in stage IIIB, and 10 months and 29.4% in stage IV. In general, the mean survival and one-year survival rates were 11 months and 43%. GCa most frequently caused grade-1 anemia (21.2%) in 165 chemotherapy cycles. CONCLUSION GCa in advanced and locally advanced NSCLC is a well-tolerated, effective alternative with its moderate toxicity

Keywords

• Gemcitabine,Carboplatin,Carcinoma, Non-Small-Cell Lung,Survival,Drug Toxicity

İleri ve lokal ileri evre küçük hücreli dışı akciğer kanserinde gemsitabin ve karboplatin kombinasyonu

Öz

AMAÇ İleri ve lokal ileri evre küçük hücreli dışı akciğer kanserinde (KHDAK) gems it abin (G) ve karb o pl atin (Ca) komb inasyonunun ant itümör etk i nliği, toks is it esi ve yaşam sür esi sonuçl arı değerlendirildi. GEREÇ VE YÖNTEM Histopatolojik olarak KHDAK teşhis edilen, ECOG 0-2 performansında olan daha önce kemoterapi uygulanmamış 41 hasta (40 erkek, 1 kadın; ort. yaş 59; dağılım 43-72) çalışmaya alındı. BULGULAR Tam yanıt (CR) %2,43 ve kısmi yanıt (PR) %34,1 oranında oldu. Evre IIIB'de CR %4,2, PR %41,7, evre IV'de CR %0 ve PR %23,5; evre IIIB'de ortalama yaşam süresi 14 ay ve bir yıllık sağkalım %54,2 iken, evre IV'de 10 ay ve %29,4 bulundu. Genel olarak, ortalama yaşam süresi 11 ay ve bir yıllık sağkalım %43 oldu. Yüz altmış beş kür GCa tedavisi sonrası en sık (%21,2) görülen ilaç toksisitesi grade-1 anemi oldu. En sık (%7,87) hematolojik olmayan toksisite bulantı ve kusma idi. SONUÇ Gemsitabin ve karboplatin, ileri ve lokal ileri evre KHDAK'de iyi tolere edilen, ılımlı toksisitesi ile etkin bir alternatif kombinasyondur.

Anahtar Kelimeler

• Gemsitabin, karboplatin, küçük hücreli dışı akciğer kanseri, toksisite, yaşam süresi.

Kaynakça

1. 1. Pretreatment evaluation of non-small-cell lung cancer. The American Thoracic Society and The European Respiratory Society. Am J Respir Crit Care Med 1997;156(1):320-32.
2. 2. Göker E, fianl› A, Uslu R, Mesut A. Akci¤er kanserlerinde kemoterapi. In: Haydaro¤lu A, editor. Akci¤er kanserleri tan› ve tedavi. ‹zmir: Ege Üniversitesi Bas›mevi; 2000. p. 223-36.
3. 3. Ettinger DS, Cox JD, Ginsberg RJ, Komaki R, Kris MG, Livingston RB, et al. NCCN Non-Small-Cell Lung Cancer Practice Guidelines. The National Comprehensive Cancer Network. Oncology (Williston Park) 1996;10(11 Suppl):81-111.
4. 4. Aygencel fi, Öztürk GC. Akci¤er kanserinin palyatif tedavisinde güncel yaklafl›mlar. In: Hastürk S, Yüksel M, editors. Akci¤er kanseri. ‹stanbul: Bilmedya Grup Yay›nevi; 2000. p. 339-50.
5. 5. Rapp E, Pater JL, Willan A, Cormier Y, Murray N, Evans WK, et al. Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer- -report of a Canadian multicenter randomized trial. J Clin Oncol 1988;6(4):633-41.
6. 6. Souquet PJ, Chauvin F, Boissel JP, Cellerino R, Cormier Y, Ganz PA, et al. Polychemotherapy in advanced non small cell lung cancer: a meta-analysis. Lancet 1993;342(8862):19-21.
7. 7. Thatcher N, Ranson M, Lee SM, Niven R, Anderson H. Chemotherapy in non-small cell lung cancer. Ann Oncol 1995;6 Suppl 1:83-95.
8. 8. Cojean I, Le Chevalier T. Chemotherapy of stage IIIB and IV non-small-cell lung cancer. Ann Oncol 1995;6 Suppl 3:S41-4.

9. 9. Chemotherapy in non-small cell lung cancer: a metaanalysis using updated data on individual patients from 52 randomised clinical trials. Non-small Cell Lung Cancer Collaborative Group. BMJ 1995;311(7010):899-909.
10. 10.Crinò L. Chemotherapy in advanced non-small-cell lung cancer. The experience of Italian Cooperative Groups. Ann Oncol 1995;6 Suppl 3:S45-7.
11. 11. Leung WT, Shiu WC, Pang JC, Lau J, Tao M, Leung SF, et al. Combined chemotherapy and radiotherapy versus best supportive care in the treatment of inoperable non-small-cell lung cancer. Oncology 1992;49(5):321-6.
12. 12. Sause W, Kolesar P, Taylor S IV, Johnson D, Livingston R, Komaki R, et al. Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. Chest 2000;117(2):358-64.
13. 13. Smith IE, O'Brien ME, Talbot DC, Nicolson MC, Mansi JL, Hickish TF, et al. Duration of chemotherapy in advanced non-small-cell lung cancer: a randomized trial of three versus six courses of mitomycin, vinblastine, and cisplatin. J Clin Oncol 2001;19(5):1336-43.
14. 14.Cullen MH, Billingham LJ, Wo o d r o ffe CM, Chetiyawardana AD, Gower NH, Joshi R, et al. Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life. J Clin Oncol 1999;17(10):3188-94.
15. 15. Le Chevalier T, Brisgand D, Douillard JY, Pujol JL, Alberola V, Monnier A, et al. Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced nonsmall-cell lung cancer: results of a European multicenter trial including 612 patients. J Clin Oncol 1994;12(2):360-7.
16. 16. Stephens RJ, et al. The big lung trial-determining the value of cisplatin-based chemotherapy for all patients with NSCLC: Prelim›nary results in the supportive care setting 38 th Ann Meeting of ASCO May 18-21, 2002 / Orlando, Florida, Abstract 1161.
17. 17. D em ir e lli FH, Özg ür o ¤lu M, Demir G. Kanser kem ot er ap isi uygulama ilkeleri. ‹stanbul; 1997. p. 1-132. 18. Chendra P, Belant MD. Paclitaxel and dosetaxel combinations in non small cell lung cancer. Chest 2000;117:144-51.
18. 19. Langer CJ, Leighton JC, Comis RL, O'Dwyer PJ, McAleer CA, Bonjo CA, et al. Paclitaxel and carbo- platin in combination in the treatment of advanced non-small-cell lung cancer: a phase II toxicity, response, and survival analysis. J Clin Oncol 1995;13(8):1860-70.
19. 20. Mountain CF. The international system for staging lung cancer. Semin Surg Oncol 2000;18(2):106-15.
20. 21. WHO Handbook for reporting of cancer treatment. 1979.
21. 22. Y›lmaz U, Yaln›z E, Utkaner G, Yaln›z Ö, Yüksel M, Kamal› Ü. Lokal ilerlemifl ve metastatik küçük hücreli d›fl› akci¤er kanserinde ifosfamid, vinblastin ve mitomisin etkinli¤i. Tüberküloz ve Toraks Derg i s i 1998;48:44-50.
22. 23. Gündo¤du C, Karalezli A, Dursun G, M›s›rl› F, Boyac› H, Yurdakul M ve ark. “Küçük hücreli olmayan akci¤er kanserlerinde iki kemoterapi kombinasyonunun karflılafltırılması. Mitomisin, Etoposide, ve cisplatin (MVC) kombinasyonuna karflı mitomycin, ifosfamide ve cisplatin (M‹C)”. Solunum Hastal›klar› 1994;5:317-25.
23. 24. Ettinger DS, Finkelstein DM, Sarma RP, Johnson DH. Phase II study of paclitaxel in patients with extensivedisease small-cell lung cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol 1995;13(6):1430-5.
24. 25. Ginsberg RJ, Kris MG, Armstrong JG. Cancer of the lung. In: De Vita VT, Hellman S, Rosenbert SA, editors. Cancer: principles and practice of oncology. 4th ed. Philadelphia, PA: JB Lippincott; 1993. p. 673-723.
25. 26. Lilenbaum RC, Green MR. Novel chemotherapeutic agents in the treatment of non-small-cell lung cancer. J Clin Oncol 1993;11:1391-402.
26. 27. Hansen HH, Lund B. Single agent therapy with gemcitabine in lung cancer: a rewiew. Lung Cancer 1994;11:28-9.
27. 28. Anderson H, Lund B, Bach F, Thatcher N, Walling J, Hansen HH. Single-agent activity of weekly gemcitabine in advanced non-small-cell lung cancer: a phase II study. J Clin Oncol 1994;12(9):1821-6.
28. 29. Abratt RP, Bezwoda WR, Falkson G, Goedhals L, Hacking D, Rugg TA. Efficacy and safety profile of gemcitabine in non-small-cell lung cancer: a phase II study. J Clin Oncol 1994;12(8):1535-40.
29. 30. Le Chevalier T, Gottfried M, Gatzemeier U, Shepherd F, Weynants P, Cottier B, et al. A phase II multicenter study of gemcitabine in non small cell lung cancers. [Article in French] Bull Cancer 1997;84(3):282-8. [Abstract]
30. 31. Zatloukal P, Petruzelka L, Zemanová M, Kolek V, Skricková J, Pesek M, et al. Gemcitabine plus cisplatin vs. gemcitabine plus carboplatin in stage IIIb and IV non-small cell lung cancer: a phase III randomized trial. Lung Cancer 2003;41(3):321-31.
31. 32. Thomas P, Robinet G, Ferri-Dessens RM, Léna H, Gouva S, Vernejoux JM, et al. Phase I trial of gemcitabine and carboplatin in metastatic non-small-cell lung cancer: a Groupe Français de PneumoCancérologie Study. Lung Cancer 2002;36(2):191-8.
32. 33.Rudd RM, Gower NH, Spiro SG, Eisen TG, Harper PG, Littler JA, et al. Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-small-cell lung cancer: a phase III randomized study of the London Lung Cancer Group. J Clin Oncol 2005;23(1):142-53.
33. 34. Mazzanti P, Massacesi C, Rocchi MB, Mattioli R, Lippe P, Trivisonne R, et al. Randomized, multicenter, phase II study of gemcitabine plus cisplatin versus gemcitabine plus carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer 2003;41(1):81-9.
34. 35. Danson S, Middleton MR, O’Byrne KJ, Clemons M, Ranson M, Hassan J, et al. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer 2003;98(3):542-53.
35. 36.Bonomi PD, Finkelstein DM, Ruckdeschel JC, Blum RH, Green MD, Mason B, et al. Combination chemotherapy versus single agents followed by combination chemotherapy in stage IV non-small-cell lung cancer: a study of the Eastern Cooperative Oncology Group. J Clin Oncol 1989;7(11):1602-13.
36. 37. Green MR, Kreisman H, Lickart S, et al. Carboplatin in non-small cell lung cancers: The Cancer and Leukemia Group B experience. Carboplatin (JM-9). In: Bunn PA, Canetta R, Ozols R, et al. (editors). Current perspectives and future directions. Philadelphia, PA: Saunders; 1990. p. 301-6.
37. 38.Çakan A, Erbaycu AE, Aksel N, Özsöz A. Akci¤er kanserli olgularda kemoterapi sonras› geliflen hematolojik komplikasyonlar. Solunum Derg i s i 2004;6(2):53-61.