Medication for the treatment of lung cancer: Emphasis on aerosolized chemotherapy
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Master’s Degree Student, Laboratory of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, National and Kapodistrian University of Athens, Greece
Professor of Biopharmaceutics and Pharmacokinetics, Laboratory of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece
Panos Macheras   

School of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis, 157 71 Athens
Pneumon 2012;25(3):298–304
Lung cancer is fast becoming the leading cause of death from malignant disease, not only in men but also in women. The prevention of lung cancer entails abstaining from cigarette smoking, which is the main risk factor. The low survival rate of patients suffering from lung cancer, along with the adverse side-effects of chemotherapy in current use, creates a fundamental need for the development of new therapeutic agents and new methods of administration. This review focuses on the anatomical and clinical pathology of lung cancer and the medications currently prescribed in clinical practice for its treatment. Emphasis is given to the administration of anticancer drugs using dry powder inhalers. Aerosolized chemotherapy is described and its advantages and disadvantages are delineated. Research programmes and clinical studies aiming at the formulation of the known anticancer drugs in dry powder aerosols are highlighted.
Geddes DM. The natural history of lung cancer. Br J Dish Chest, 1979; 73(1):1-17.
Aaronchick JM. Lung cancer: epidemiology and risk factors. Semin Roentgenol, 1990; 25:5.
Stein JH, Hatton JJ, Kohler P. Stein Pathology. Ιατρικές εκδόσεις Πασχαλίδης, 2003.
Velsemes M. Καρκίνος του Πνεύμονα. Παθολογία ΔΕΠ, 2002; 274-280.
Iannuzzi MC, Miller Y. The genetic predisposition to lung cancer. Semin Res Med 7, 1986; 327.
Spiro SG. Carcinoma of the lung. Eur Resp Mon, 1995; 1(1): 1–394.
Lyubsky S, Jacobson MJ. Lung Cancer: Making the diagnosis. Chest, 1991; 100:511.
Patakas D. “Επίτομη Πνευμονολογία” Κεφ. 17 - Ιστοπαθολογία, σελ. 301-302.
Kotoulas XS. Τι πρέπει να γνωρίζουμε για τον καρκίνο του πνεύμονα. Στρατιωτική Επιθεώρηση, Μαρ-Απρ 2003.
American Cancer Society,
Mouratidou D, Andreadis X, Papazisis K, et al. Βασικά Χημειοθεραπευτικά Σχήματα. Αντικαρκινικό Νοσοκομείο Θεσ/νίκης «Θεαγένειο», Ιούλιος 2009.
Bang Y, Kwak EL, Shaw T, et al. Clinical activity of the oral ALK inhibitor PF-02341066 in ALK-positive patients with non-small cell lung cancer (NSCLC). J Clin Oncol, (suppl; abstr 3), 2010; 28:7s.
Arteaga CL, Khuri F, Krystal G, et al. Overview of rationale and clinical trials with signal transduction inhibitors in lung cancer. Sem Oncol 2002; 29: 15-26.
Herbst RS, Langer CJ. Epidermal growth factor as a target for cancer treatment: the emerging role of IMC-C225 in the treatment of lung and head and neck cancers. Sem Oncol 2002; 29: 27S-36S.
Fukuoka M, Yano S, Giaccone G, et al. Final results from a phase II trial of ZD1839 (Iressa) for patients with advanced non-small cell lung cancer (IDEAL 1). Proc Am Soc Clin Oncol 2002; 21: 1188.
Kotantoula G, Winterhalder RC. Χημειοπροφύλαξη στον καρκίνο του πνεύμονα. ΠΝΕΥΜΩΝ, 2003, Τεύχος 2 Μάιος-Αύγουστος.
Lord RVN, Brabender J, Gandara D, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res, 2002; 8:2286-2291.
Rosell R, Danenberg K, Alberola V, et al. Ribonucleotide reductase subunit 1 subunit 1 mRNA expression and survival in gemcitabine/cisplatintreated advanced non-small-cell lung cancer patients. Clin Cancer Res, 2004; 10:1318-1325.
Davidson JD, Ma L, Flagella M, et al. An increase in the expression of ribonucleotide reductase subunit 1 large subunit 1 is associated with gemcitabine resistance in non-small cell lung cancer cell lines. Cancer Res, 2004; 64:3761-3766.
Bergman A, Eijk P, van Haperen V, et al. In vivo induction of resistance to gemcitabine results in increased expression of ribonucleotide reductase subunit 1 subunit M1 as a major determinant. Cancer Res,2005; 65:9510-9516.
Bepler G, Kusmartseva I, Sharma S, et al. RRM1-modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small cell lung cancer. J Clin Oncol, 2006; 24:4731-4737.
Stubbe J. Ribonucleotide reductase subunit 1s in the twenty-first century. Proc Natl Acad Sci USA, 1998; 95:2723-2724.
Reed E. ERCC1 and clinical resistance to platinum-based therapy. Clin Cancer Res, 2005; 11:6100-6102.
Simon G, Sharma A, Li X, et al. Feasibility and Efficacy of Molecular Analysis-Directed Individualized Therapy in Advanced Non-Small-Cell Lung Cancer. J Clin Oncol, 2007; 25:2741-2746.
Laube BL. The expanding role of aerosols in systemic drug delivery, gene therapy, and vaccination. Respir Care. ©Daedalus Enterprises, 2005; 50 (9): 1161-1174.
Smaldone GC. Advances in aerosols: adult respiratory disease. J Aerosol Med, 2006; 19: 36-46.
Hureaux J, Lagarce F, Gagnadoux F, et al. Lipid nanocapsules: Ready-to-use nanovectors for the aerosol delivery of paclitaxel. Eur J Pharm Biopharm 73, 2009; 06.013:239-246.
Gagnadoux F, Hureaux J, Vecellio L, et al. Aerosolized chemotherapy. J Aerosol Med Pulm Drug Deliv, 2008; 21:61-70.
Maillet A, Congy-Jolivet N, Les Guellec S, et al. Aerodynamical, immunological and pharmacological properties of the anticancer antibody cetuximab following nebulization. Pharm Res, 2008; 25:1318-26.
El-Gendy N, Berkland C. Combination chemotherapeutic dry powder aerosols via controlled nanoparticle agglomeration. Pharm Res 26, July 2009; 1752-1763.
Sharma S, White D, Imondi AR, Placke ME, Vail DM, Kris MG. Development of inhalational agents for oncologic use. J Clin Oncol, 2001; 19: 1839-1847.
Schevchenko IT, Resnik GE. Inhalation of chemical substances and oxygen in radiotherapy of bronchial cancer. Neoplasma, 1968; 15: 419-426.
Camus P, Fanton A, Bonniaud P, Camus C, Foucher P. Interstitial lung disease induced by drugs and radiation. Respiration, 2004; 71: 301-326.
Camus P. Interstitial lung disease in patients with non-smallcell lung cancer: causes, mechanisms and management. Br J Cancer 91 (suppl 2): S1-S2, 2004.
Wittgen BP, Kunst PW, van der Born K, et al. Phase I study of aerosolized SLIT cisplatin in the treatment of patients with carcinoma of the lung. Clin Cancer Res, 2007; 13: 2414-2421.
Dandan Y, Wiedmann TS. Inhalation adjuvant therapy for lung cancer. J Aer Med Pulm Del, 2010; 23(4): 181-187.
Labiris NR, Dolovich MB. Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol, 2003; 56: 588-599.
Bhavna ???, Αhmad FJ, Khar RK, Sultana S, Bhatnagar A. Techniques to develop and characterize nanosized formulation for salbutamol sulfate. J Mater Sci Mater Med, 2008; 20:S71–S76.
Labiris NR, Dolovich MB. Pulmonary drug delivery. Part II: the role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol, 2003; 56: 600-612.
Wittgen BP, Kunst PW, Perkins WR, Lee JK, Postmus P E. Assessing a system to capture stray aerosol during inhalation of nebulized liposomal cisplatin. J Aerosol Med, 2006; 19: 385-391.
Azarmi S, Tao X, Chen H, et al. Formulation and cytotoxicity of doxorubicin nanoparticles carried by dry powder aerosol particles. Int J Pharm. 2006; 319: 155-161.
Vlastos F. Θεραπεία του καρκίνου του πνεύμονα: παρόν και μέλλον. Πνεύμων, 2004; 17: 272-288.
Otterson GA, Villalona-Calero MA, Sharma S, et al. Phase I study of inhaled doxorubicin for patients with metastatic tumors to the lungs. Clin Cancer Res. 2007; 13(4):1246-52.
Haynes A, Shaik MS, Chatterjee A, Singh M. Formulation and evaluation of aerosolized celecoxib for the treatment of lung cancer. Pharm Res, 2005; 22(3):427-39.
Fulzele SV, Shaik MS, Chatterjee A, Singh M. Anti-cancer effect of celecoxib and aerosolized docetaxel against human non-small-cell lung cancer cell line, A549. J Pharm Pharmacol, 2006; 58: 327-336.
Gagnadoux F, Leblond V, Vecellio L, et al. Gemcitabine aerosol: in vitro antitumor activity and deposition imaging for preclinical safety assessment in baboons. Cancer Chemother Pharmacol, 2006; 58: 237-244.
Min R, Li T, Du J, Zhang Y, Guo J, Lu WL. Pulmonary gemcitabine delivery for treating lung cancer: pharmacokinetics and acute lung injury aspects in animals. Can J Physiol Pharmacol 2008; 86: 288-298.
Wang Z, Chen HT, Roa W, Finlay WH. Farnesol for aerosol inhalation: nebulization and activity against human lung cancer cells. J Pharm Pharmaceut Sci, 2003; 6: 95-100.
Qamar W, Sultana S. Farnesol ameliorates massive inflammation, oxidative stress and lung injury induced by intratracheal instillation of cigarette smoke extract in rats: An initial step in lung chemoprevention. Chem Biol Interac., 2008; 176: 79-87.
Tatsumura T, Koyama S, Tsujimoto M, Kitagawa M, Kagamimori S. Further study of nebulisation chemotherapy, a new chemotherapeutic method in the treatment of lung carcinomas: fundamental and clinical. Br J Cancer, 1993; 68: 1146-1149.
Lefranc F, Facchini V, Kiss R. Proautophagic drugs: a novel means to combat apoptosis-resistant cancers, with a special emphasis on glioblastomas. Oncologist, 2007; 12: 1305 1403.
Choong NW, Mauer AM, Hoffmann PC, et al. Phase II trial of temozolomide and irinotecan as second line treatment for advanced non-small-cell lung cancer. J Thorac Oncol, 2006; 1: 732-733.
Tamaskar L, Mekhail T, Dreicer R, et al. Phase I trial of weekly docetaxel and daily temozolomide in patients with metastatic disease. Invest New Drugs, 2008; 26: 553-559.
Kouroussis C, Vamvakas L, Vardakis N, et al. Continuous administration of daily low-dose temozolomide in pretreated patients with advanced non-small-cell lung cancer: a phase II study. Oncology, 2009; 76: 112-117.
Wauthoz N, Deleuze P, Hecq J, et al. In vivo assessment of temozolomide local delivery for lung cancer inhalation therapy. Eur J Pharmaceut Sci., 2010; 39: 402-411.
Anderson PM, Markovic SN, Sloan JA, et al. Aerosol granulocyte macrophage-colony stimulating factor: a low toxicity, lungspecific biological therapy in patients with lung metastases. Clin Cancer Res, 1999; 5: 2316-2323.
Gautam A, Waldrep JC, Densmore CL, et al. Growth inhibition of established B16-F10 lung metastases by sequential aerosol delivery of p53 gene and 9-nitrocamptothecin. Gene Therapy, 2002; 9: 353-357.
Koshkina NV, Waldrep JC, Knight V. Camptothecins and lung cancer: improved delivery systems by aerosol. Current Cancer Drug Targets, 2003; 3: 251-264.
Zou Y, Tornos C, Qiu X, Lia M, Perez-Soler R. p53 aerosol formulation with low toxicity and high efficiency for early lung cancer treatment. Clin Cancer Res, 2007; 13: 4900-4908.