Çiğdem PAPİLA, Firuz ÇELİKOĞLU, Seyhan İ. ÇELİKOĞLU

Akciğer kanserinde sitotoksik ilaçların tümör içine direkt enjeksiyonu ile uygulanan endobronşiyal kemoterapi

Endobronşiyal intratümöral kanser kemoterapisi (EİTK), bir veya birden fazla sitotoksik ilacın fleksibl bronkoskop aracılığı ile bir kateter-iğneden doğrudan doğruya tümör dokusu içine enjekte edilmesi ile uygulanan girişimsel bir bronkoskopi yöntemidir. EİTK, havayolu içinde yer alan tümör kitlesi üzerindeki etkisi yanında tümöre komşu dokulardaki kanser hücrelerini de tahrip etmesi ile özellik gösterir. Termik ve mekanik girişimsel bronkoskopi yöntemlerinden farklı olarak normal hücrelere zarar vermeksizin, kanserli hücreler üzerinde spesifik bir etki yapar. Bu spesifik etki prensip bakımından brakiterapi ve fotodinamik tedavinin etkisine benzer. Tümör içine enjeksiyonla verilen ilaç kanserli hücreleri nekrozlaştırdığı halde ortadan kaldıramaz. Bu bakımdan obstrüksiyonun acilen açılması gereken durumlarda endobronşiyal tümör kitlesinin mekanik veya termik girişimsel yöntemlerle ortadan kaldırılması gerekir. EİTK' nin radyoterapi veya cerrahi tedaviden önce kullanıldığı zaman loko-rejyonel bir kemoterapi işlevi yaptığı öne sürülmüştür. Tümör içine enjeksiyonun intravenöz kemoterapiye nazaran en önemli avantajı, tümör kitlesi içinde yüksek ilaç konsantrasyonu sağlandığı halde, sistemik toksik bir etkinin oluşmamasıdır. Hasta için hiç bir risk taşımayan, hastane için özel bir donanım masrafı gerektirmeyen bu yöntem girişimsel bronkoksopi uygulanan özelleşmiş merkezlerde kolayca uygulanabilir. Bu derlemede, metodun bilimsel ilkeleri açıklanarak endolüminal yerleşim bulunan akciğer kanseri olgularında diğer standart kanser tedavileri ile beraber kullanıldığı takdirde sağlayacağı potansiyel fayda irdelenmiştir.

Endobronchial chemotherapy by direct injection of cytotoxic drugs into the tumor in lung cancer

Intratumoral injection of one or several conventional cytotoxic drugs directly into the tumoral tissue through a flexible bronchoscope by means of an ordinary needle-catheter which is called “endobronchial intratumoral chemotherapy (EITC)” is a therapeutic paradigm of bronchoscopic interventional procedure. The achievement of intratumoral chemotherapy should never be considered merely an ablation technique of endobronchial tumor bulk alike the other endoscopic ablative procedures; but, it exerts most importantly an additional chemotherapeutic specific effect on malignant cells through the action of cytotoxic drug. Owing to its specific effect it has a similarity to brachytherapy and photodynamic therapy. Indeed, in addition to the advantage of the initial eradication of tumoral burden inside the airway lumen in conjunction with mechanical resection, intratumoral delivery of cytotoxic drugs also provides a loco-regional neo-adjuvant therapy for irradiation or surgery. It is a real chemotherapy which differs from intravenous chemotherapy only by its route of delivery. The advantages of intratumoral injection technique include an increased precision in the local delivery of therapeutic materials, complete perfusion of the lesion, higher local tissue concentrations, as well as fewer systemic side effects. The endobronchial intratumoral chemotherapy has not any adverse effect for the patients, does not require any additional instrumentation and could be easily performed in any specialized interventional bronchoscopy unit. In this comprehensive review of “endobronchial intratumoral chemotherapy via-needle catheter”, our objective is to define and categorize the efficiency of this therapeutic paradigm of bronchoscopic intervention.

PDF

___

1. Cersosomo RJ. Lung cancer: A review. Am J Health Syst Pharm 2002; 59: 611-42.
2. Parkin DM. Global cancer statistics in the year 2000. Lancet Oncol 2001; 2: 533-43.
3. Matthews MJ. Problems in morphology and behavior of bronchopulmonary malignant disease. In: Israel L, Chahinian AP (eds). Lung Cancer: Natural History, Prognosis and Therapy. New York: Academic Press, 1976: 23-62.
4. Spiro SG, Porter JC. Lung cancer-where are we today?Current advances in staging and nonsurgical treatment.Am J Resp Crit Care Med 2002; 166: 1166-96.
5. Trovo MG, Minatel E, Veronesie A, et al. Combined radiotherapy and chemotherapy vs. radiotherapy alone in locally advanced bronchogenic carcinoma: A randomized study. Cancer 1990; 65: 400-4.
6. Pradier O, Laderer K, Hille A, et al. Concurrent low-dose cisplatin and thoracic radiotherapy in patients with inoperable stage III non-small-cell lung cancer: A phase II trial reference to the hemoglobin level as prognostic parameter. J Cancer Res Clin Oncol 2005; 131: 261-9.
7. Jemal A, Murray T, Ward E, et al. Cancer Statistics 2005. Cancer J Clin 2005; 55: 10-30.
8. Ginsberg RJ, Vokes EE, Ruben A. Non-small cell lung cancer. In: De Vita VT, Hellman S, Rosenberg SA (eds).Cancer: Principles and Practice of Oncology. 5th ed. Philadelphia:JB Lippincott-Raven, 1997: 858-911.
9. Luomanen RKJ, Watson WL. Autopsy findings. In: Watson WL (ed). Lung Cancer. A Study of Five Thousand Memorial Hospital Cases. St Louis: Mosby Co, 1968: 504-10.
10. Çelikoğlu S, Karayel T, Demirci S ve ark. Bronkojenik karsinomda fleksibl fiberoptik bronkoskop aracılığı ile lazer fotorezeksiyonu. İstanbul Tıp Fak Mecm 1994; 57:60-3.
11. Freitag I, Macha HN, Loddenkemper R. Interventional bronchoscopic procedures. Eur Respir Monogr 2001; 6:272-304.
12. Ernst A, Feller-Kopman D, Becker HD, Mehta AC. Central airway obstruction. Am J Respir Crit Care Med 2004;169: 1278-97.
13. Bolliger CT, Mathur PN. ERS/ATS statement on interventional pulmonology. Eur Respir J 2002; 19: 356-73.
14. Celikoglu SI, Karayel T, Demirci S, et al. Direct injection of several anticancer drugs into endobronchial malignant tumor in the palliation of major airway obstruction (abstract). Eur Respir J 1991; 4 (Suppl 14): 303.
15. Celikoglu SI, Celikoglu F, Karayel T, et al. Direct injection of anticancer drugs into endobronchial tumors for major airway obstruction. Post Grad Med J 1997; 73: 159-62.
16. Celikoglu F, Celikoglu SI. Intratumoral chemotherapy with 5-fluorouracil for palliation of bronchial cancer in patients with severe airway obstruction. J Pharm Pharmacol 2003; 55: 1441-8.
17. Celikoglu F, Celikoglu SI, York AM, Goldberg PE. Intratumoral administration of cisplatin through a bronchoscope followed by irradiation for treatment of inoperable non-small cell obstructive lung cancer. Lung Cancer 2006; 51: 225-36.
18. Celikoglu SI, Celikoglu F, Goldberg PE. Endobronchial intratumoral chemotherapy (EITC) followed by surgery in early non-small-cell lung cancer with polypoid growth causing erroneous impression of advanced disease. Lung Cancer 2006; 54: 339-46.
19. Celikoglu SI, Celikoglu F, Goldberg PE. Intratumoral chemotherapy through a flexible bronchoscope. J Bronchol 2004; 11: 260-5.
20. Çelikoğlu S, Karayel T, Çelikoğlu F ve ark. Büyük hava yollarında obstrüksiyon yapan bronş kanserlerinde fleksibl bronkoskop aracılığı ile çeşitli antikanser ilaçların direkt enjeksiyonunun palyatif tedavideki değeri (ön bildiri). İstanbul Tıp Fak Mecm 1993; 56: 32-40.
21. Liu M, Ma P, Lu Z. Local chemotherapy by fibrobroncoscopy for advanced broncogenic carcinoma. Chin J Tuberc Respir Dis 2000; 23: 550-1.
22. Goldberg EP, Hadba HR, Almond BA, Marotta JS. Intratumoral cancer chemotherapy and immunotherapy: Opportunities for non-systemic preoperative drug delivery. J Pharm Pharmacol 2002; 54: 159-80.
23. Mathisen DJ, Grillo HC. Endoscopic relief of malignant airway obstruction. Ann Thorac Surg 1989; 48: 469-75.
24. Bateman JC. Palliation of cancer in human patients by maintenance therapy with NN’N’’- triethylene thiophosphoramide and N-(3-oxapentamerthylene)-N’N’’-diethylene phoshoramide. Ann N Y Acad Sci 1958; 68: 1057-71.
25. Brincher H. Direct intratumoral chemotherapy. Crit Rev Oncol Hematol 1993; 15: 91-8.
26. Hayata Y, Ohbo K, Ogava I, Taira O. Immunotherapy for lung cancer cases using BCG or BCG cell-wall skeleton: Intratumoral injections. Gann. Monogr Cancer Res 1978; 21: 51.
27. Lardinois D, Brack T, Gaspert A, et al. Bronchoscopic radioisotope injection for sentinel lymph-node mapping in potentially resectable non-small-cell-lung-cancer. Eur J Cardio-Thorac Surg 2003; 23: 824-7.
28. Seymour CW, Krimsky WS, Sager J, et al. Transbronchial needle injection: A systemic review of a new diagnostic and therapeutic paradigm. Respiration 2006; 73: 78-89.
29. Sandler AB, Nemunaitis J, Denham C, et al. Phase III trial of gemcitabine plus Cisplatin versus Cisplatin alone in patients with locally advanced or metastatic non-small lung cancer. J Clin Oncol 2000; 18: 122-30.
30. Gatzemeir U, Von Pawel L, Gottfried M, et al. Phase III comparative study of high dose Cisplatin versus a combination of paclitaxel and Cisplatin in patients with advanced non-small lung cancer. Proc Am Soc Clin Oncol 1998; 17: 454a.
31. Shaake -Koning C, van den Bogaert W, Dalesio O, et al. Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. N Engl J Med 1992; 326: 524-30.
32. Shaake-Konig C, van den Bogaert W, Daleiso O, et al. Radiosensitization by cytotoxic drugs. The EORTC experience by radiotherapy and lung cancer cooperative groups. Lung Cancer 1994; 10(Suppl): 263-70.
33. Yapp DT, Lloyd DK, Zhu E, Lehnert SM. The potentiation of the effect of radiation treatment by intratumoral delivery of cisplatin. Int J Radiat Oncol Rio Phys 1998; 42: 413-20.
34. Burris HA III, Vogel CL, Castro D, et al. Intratumoral cisplatin/ epinephrine- injectable gel as a palliative treatment for accessible solid tumors: A multicenter pilot study. Otolaryngol Head Neck Surg 1998; 118: 496-503.
35. Vogl TJ, Engelmann K, Mack MG, et al. CT-guided intratumoral administration of cisplatin/epinephrine gel for treatment of malignant liver tumors. Brit J Cancer 2002; 86: 524-9.
36. Monga SPS, Wadleigh RW, Adib H, et al. Endoscopic treatment of gastric cancer with intratumoral cisplatin/epinephrine injectable gel: A case report. Gastrointest Endosc 1998; 48: 415-7.
37. Monga SPS, Wadleigh RW, Sharma A, et al. Intratumoral therapy of cisplatin/epinephrine injectable gel for palliation in patients with obstructive esophageal cancer. Am J Clin Oncol (CCT) 2000; 23: 386-92.
38. Vergnon JM, Schmitt T, Alamartine E, et al. Initial combined cryotherapy and irradiation for unresectable nonsmall cell lung cancer. Preliminary results. Chest 1992; 102: 1436-40.
39. Eichenhorn MS, Kvale PA, Miks VM, et al. Initial combination therapy with laser photoresection and irradiation for inoperable non-small cell carcinoma of the lung. Chest 1986; 89: 782-5.
40. Freitag L, Ernst A, Thomas M, et al. Sequential photodynamic therapy (PDT) and high dose brachytherapy for endobronchial tumor control in patients with limited bronchogenic carcinoma. Thorax 2004; 59: 790-3.