Skip to main content

Radioprotectors and Chemoprotectors in the Management of Lung Cancer

  • Chapter
  • First Online:
  • 1761 Accesses

Part of the book series: Medical Radiology ((Med Radiol Radiat Oncol))

Abstract

Lung cancer is the leading cause of cancer death in most developed countries. The prognosis remains poor with an overall survival rate at 5 years of only about 15%. Between 70 and 85% of all cases are histologically classified as non-small cell lung carcinoma (NSCLC). Radiation therapy has traditionally been the treatment of choice for locally advanced disease and medically inoperable early stage NSCLC. However radiation therapy alone was not effective treatment for patients with locally advanced NSCLC. The addition of cytotoxic drugs to radiotherapy considerably improves treatment outcome, and the combination of chemotherapy with radiotherapy has become common practice for the treatment of locally advanced lung cancer. The addition of chemotherapy to radiotherapy has two principal objectives: one, to increase the chance of local tumor control and two, to eliminate metastatic disease outside of the radiation field. Several randomized trials have shown improvement of local control and survival by application of concurrent chemotherapy rather than sequential chemotherapy followed by radiation treatment. This combined treatment approach results in median survival times of 13 to 14 months and survival rates at 5 years as high as 15 to 20%. These improvements have been achieved by using standard chemotherapeutic agents, primarily cisplatin-based drug combinations. However, concurrent chemoradiotherapy has increased significant normal tissue toxicity such as esophagitis and pneumonitis. Therefore normal tissue protectors without protective cancer cells became necessary to improve therapeutic ratio. We will discuss mechanism and efficacy of Amifostine to protect normal tissue followed by other normal tissue protectors or molecular targeted treatment without increasing normal tissue damage e.g., prostanoids (COX-2) inhibitors, Growth factor and Cytokines inhibitors, Basic and other inhibitors targeting Fibroblast Growth Factor, Karatinocyte Growth Factors, Epidermoid Growth Factor Receptor, Pentoxifylline, Angiotensin-Converting Enzyme Flavopiridol Poly(ADP-Ribose) Polymerase, Bcl-2 , and Efaproxaril, as well as Radioprotective Gene Therapy/ Antioxidant Therapy: and Superoxide Dismutase

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Albert JM, Cao C, Kim KW et al (2007) Inhibition of poly(ADP-ribose) polymerase enhances cell death and improves tumor growth delay in irradiated lung cancer models. Clin Cancer Res 13(10):3033–3042

    Article  PubMed  CAS  Google Scholar 

  • American Cancer Society (2011) Global Cancer Facts and Figures, 2nd edn. American Cancer Society, Atlanta

    Google Scholar 

  • Antonadou D, Coliarakis N, Synodinou M et al (2001) Randomized phase III trial of radiation treatment plus/minus amifostine in patients with advanced stage lung cancer. Int J Radiat Oncol Biol Phys 51:915–922

    Article  PubMed  CAS  Google Scholar 

  • Antonadou D, Throuvalas N, Petridis A et al (2003) Effect of amifostine on toxicities associated with radiochemotherapy in patients with locally advanced non-small cell lung cancer. Int J Radiat Oncol Biol Phys 57:402–408

    Article  PubMed  CAS  Google Scholar 

  • Bardet E, Martin L, Calais G et al (2002) Preliminary data of the GORTEC 2000–02 phase III trial comparing intravenous and subcutaneous administration of amifostine for head and neck tumors treated by external radiotherapy. Semin Oncol 29:57–60

    Article  PubMed  CAS  Google Scholar 

  • Baselga J, Norton L, Masui H et al (1993) Antitumor effects of doxorubicin in combination with anti-epidermal growth factor receptor monoclonal antibodies. J Natl Cancer Inst 85:1327–1233

    Article  PubMed  CAS  Google Scholar 

  • Baselga J, Pfister D, Cooper MR et al (2000) Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. J Clin Oncol 18:904–914

    PubMed  CAS  Google Scholar 

  • Baumann M, Krause M, Zips D et al (2004) Molecular targeting in radiotherapy of lung cancer. Lung Cancer 45(suppl 2):S187–S197

    Article  PubMed  Google Scholar 

  • Benhar M, Engelberg D, Levitzki A (2002) Cisplatin-induced activation of the EGF receptor. Oncogene 21:8723–8731

    Article  PubMed  CAS  Google Scholar 

  • Bensadoun RJ, Schubert MM, Lalla RJ et al (2006) Amifostine in the management of radiation-induced and chemo-induced mucositis. Support Care Cancer 14:566–572

    Article  PubMed  Google Scholar 

  • Bianco C, Bianco R, Tortora G et al (2000) Antitumor activity of combined treatment of human cancer cells with ionizing radiation and anti-epidermal growth factor receptor monoclonal antibody C225 plus type I protein kinase A antisense oligonucleotide. Clin Cancer Res 6:4343–4350

    PubMed  CAS  Google Scholar 

  • Bible KC, Lensing JL, Nelson SA et al (2005) Phase 1 trial of flavopiridol combined with cisplatin or carboplatin in patients with advanced malignancies with the assessment of pharmacokinetic and pharmacodynamic end points. Clin Cancer Res 11(16):5935–5941

    Article  PubMed  CAS  Google Scholar 

  • Blumenschein GR Jr, Paulus R, Curran WJ, Robert F, Fossella F, Werner-Wasik M, Herbst R, Doescher PO, Choy H, Komaki R (2011) A phase II study of cetuximab (C225) in combination with chemoradiation in patients with stage IIIA/B non-small cell lung cancer: RTOG 0324 J Clin Oncol 29(17):231–238

    Google Scholar 

  • Bonner HS, Shaw LM (2002) New dosing regimens for amifostine: a pilot study to compare the relative bioavailability of oral and subcutaneous administration with intravenous infusion. J Clin Pharmacol 42:166–174

    Article  PubMed  CAS  Google Scholar 

  • Bonner JA, Harari PM, Giralt J et al (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:567–578

    Article  PubMed  CAS  Google Scholar 

  • Borrelli A, Schiattarella A, Mancini R et al (2009) A recombinant MnSOD is radioprotective for normal cells and radiosensitizing for tumor cells. Free Radic Biol Med 46(1):110–116

    Article  PubMed  CAS  Google Scholar 

  • Bourhis J, Blanchard P, Maillard E et al (2011) On behalf of the MAART Collaborative Group Effect of amifostine on survival among patients treated with radiotherapy: a meta-analysis of individual patient data. J Clin Oncol (in press)

    Google Scholar 

  • Bradley J, Graham MV, Winter K et al (2005) Toxicity and outcome results of RTOG 9311: a phase I–II dose escalation study using three-dimensional conformal radiation therapy in patients with inoperable non-small cell lung cancinoma. Int J Radiat Oncol Biol Phys 61:318–328

    Article  PubMed  Google Scholar 

  • Breuer R, Tochner Z, Conner MW et al (2000) Superoxide dismutase inhibits radiation-induced lung injury in hamsters. Lung 170:19–29

    Article  Google Scholar 

  • Brizel DM (2003) Does amifostine have a role in chemoradiation treatment? Lancet Oncol 4:378–380

    Article  PubMed  CAS  Google Scholar 

  • Brizel DM (2007) Pharmacologic approaches to radiation protection. J Clin Oncol 25(26):4084–4089

    Article  PubMed  CAS  Google Scholar 

  • Brizel DM, Wasserman TH, Henke M et al (2000) Phase III randomized trial of amifostine as a radioprotector in head and neck cancer. J Clin Oncol 18:3339–3345

    PubMed  CAS  Google Scholar 

  • Bruns CJ, Harbison MT, Davis DW et al (2000) Epidermal growth factor receptor blockade with C225 plus gemcitabine results in regression of human pancreatic carcinoma growing orthotopically in nude mice by antiangiogenic mechanisms. Clin Cancer Res 6:1936–1948

    PubMed  CAS  Google Scholar 

  • Burdette-Radoux S, Tozer RG et al (2004) Phase II trial of flavopiridol, a cyclin dependent kinase inhibitor, in untreated metastatic malignant melanoma. Invest New Drugs 22:315–322

    Article  PubMed  CAS  Google Scholar 

  • Calabresi CR, Almassy R, Barton S et al (2004) Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361. J Natl Cancer Inst 96(1):56–67

    Article  CAS  Google Scholar 

  • Calabro-Jones PM, Gahey RC, Smoluk GD et al (1985) Alkaline phosphatase promotes radioprotection and accumulation of WR-1065 in V79–171 cells incubated in medium containing WR-2721. Int J Radiat Biol 47:23–27

    Article  CAS  Google Scholar 

  • Camphausen K, Brady KJ, Burgan WE et al (2004) Flavopiridol enhances human tumor cell radiosensitivity and prolongs expression of gammaH2AX foci. Mol Cancer Ther 3(4):409–416

    PubMed  CAS  Google Scholar 

  • Carvajal RD, Tse A, Shah MA et al (2009) A phase II study of flavopiridol (Alvocidib) in combination with docetaxel in refractory, metastatic pancreatic cancer. Pancreatology 9(4):404–409

    Article  PubMed  CAS  Google Scholar 

  • Chopra M, Scott N, McMurray J et al (1989) A free radical scavenger. Br J Clin Pharmacol 27:396–399

    Article  PubMed  CAS  Google Scholar 

  • Choy H, Milas L (2003) Enhancing radiotherapy with cyclooxygenase-2 enzyme inhibitors: a rational advance? J Natl Cancer Inst 95:1440–1452

    Article  PubMed  CAS  Google Scholar 

  • Ciardiello F, Bianco R, Damiano V et al (1999) Antitumor activity of sequential treatment with topotecan and anti-epidermal growth factor receptor monoclonal antibody C225. Clin Cancer Res 5:909–916

    PubMed  CAS  Google Scholar 

  • Csiki I, Morrow JD, Sandler A et al (2005) Targeting cyclooxygenase-2 in recurrent non-small cell lung cancer: a phase II trial of celecoxib and docetaxel. Clin Cancer Res 11(18):6634–6640

    Article  PubMed  CAS  Google Scholar 

  • Curran WJ, Scott CB, Langer CJ et al (2003) Long-term benefit is observed in a phase III comparison of sequential versus concurrent chemo-radiation for patients with unresected stage III NSCLC: RTOG 9410. Proc Am Soc Clin Oncol 22:621 (abstr 2499)

    Google Scholar 

  • Delanian S, Baillet F, Huart J et al (1994) Successful treatment of radiation-induced fibrosis using liposomal Cu/Zn superoxide dismutase: clinical trial. Radiother Oncol 32:12–20

    Article  PubMed  CAS  Google Scholar 

  • Dest VM (2006) Radioprotectants: adding quality of life to survivorship? Semin Oncol Nurs 22(4):249–256

    Article  PubMed  Google Scholar 

  • Dickson MA, Shah MA, Rathkopf D et al (2010) A phase I clinical trial of FOLFIRI in combination with the pan-cyclin-dependent kinase (CDK) inhibitor flavopiridol. Cancer Chemother Pharmacol 66(6):1113–1121

    Article  PubMed  CAS  Google Scholar 

  • Dillman RO, Herndon J, Seagren SL et al (1996) Improved survival in stage III non-small-cell lung cancer: seven-year follow-up of Cancer and Leukemia Group B (CALGB) 8433 trial. J Natl Cancer Inst 88:1210–1215

    Article  PubMed  CAS  Google Scholar 

  • Dillman RO, Seagren SL, Propert KJ et al (1990) A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med 323:940–945

    Article  PubMed  CAS  Google Scholar 

  • Dion MW, Hussey DH, Osborne JW (1989) The effect of pentoxifylline on early and late radiation injury following fractionated irradiation of C3H mice. Int J Radiat Oncol Biol Phys 17:101–107

    Article  PubMed  CAS  Google Scholar 

  • Dispenzieri A, Gertz MA, Lacy MQ et al (2006) Flavopiridol in patients with relapsed or refractory multiple myeloma: a phase 2 trial with clinical and pharmacodynamic end-points. Haematologica 91:390–393

    PubMed  CAS  Google Scholar 

  • Donawho CK, Luo Y, Penning TD et al (2007) ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin Cancer Res 13(9):2728–2737

    Article  PubMed  CAS  Google Scholar 

  • Durand RE (1983) Radioprotection by WR-2721 in vitro and low oxygen tensions: implications for its mechanisms of action. Br J Cancer 47:387–392

    Article  PubMed  CAS  Google Scholar 

  • Durand RE, Olive PL (1989) Radiosensitization and radioprotection by BSO and WR-2721: the role of oxygenation. Br J Cancer 60:417–522

    Article  Google Scholar 

  • Eberhardt W, Pöttgen C, Stuschke M (2006) Chemoradiation paradigm for the treatment of lung cancer. Nat Clin Pract Oncol 3(4):188–199

    Article  PubMed  CAS  Google Scholar 

  • El-Rayes BF, Gadgeel S, Parchment R et al (2006) A phase I study of flavopiridol and docetaxel. Invest New Drugs 24(4):305–310

    Article  PubMed  Google Scholar 

  • Epperly MW, Bray JA, Krager S et al (1999) Intratracheal injectrion of adenovirus containing the human MnSOD transgene protects athymic nude mice from irradiation-induced organizing alveolitis. Int J Radiat Oncol Biol Phys 43:169–181

    Article  PubMed  CAS  Google Scholar 

  • Epperly MW, Gretton JA, DeFilippi SJ et al (2001) Modulation of radiation-induced cytokine elevation associated with esophagitis and esophageal stricture by manganese superoxide dismutase-plasmid/liposome (SOD2-PL) gene therapy. Radiat Res 155:2–14

    Article  PubMed  CAS  Google Scholar 

  • Epperly MW, Guo HL, Jefferson M et al (2003) Cell phenotype specific kinetics of expression of intratracheally injected manganese superoxide dismutase plasmid/liposomes (MnSOD-PL) during lung radioprotective gene therapy. Gene Ther 2:163–171

    Article  CAS  Google Scholar 

  • Fekrazad HM, Verschraegen CF, Royce M et al (2010) A phase I study of flavopiridol in combination with gemcitabine and irinotecan in patients with metastatic cancer. Am J Clin Oncol 33(4):393–397

    Article  PubMed  CAS  Google Scholar 

  • Fornier MN, Rathkopf D, Shah M et al (2007) Phase I dose-finding study of weekly docetaxel followed by flavopiridol for patients with advanced solid tumors. Clin Cancer Res 13(19):5841–5846

    Article  PubMed  CAS  Google Scholar 

  • Fuks Z, Persaud RS, Alfieri A et al (1994) Basic fibroblast growth factor protects endothelial cells against radiation-induced programmed cell death in vitro and in vivo. Cancer Res 54:2582–2590

    PubMed  CAS  Google Scholar 

  • George S, Kasimis BS, Cogswell J et al (2008) Phase I study of flavopiridol in combination with Paclitaxel and Carboplatin in patients with non-small-cell lung cancer. Clin Lung Cancer 9(3):160–165

    Article  PubMed  CAS  Google Scholar 

  • Giannopoulou E, Papadimitriou E (2003) Amifostine has antiangiogenic properties in vitro by changing the redox status of human endothelial cells. Free Radic Res 37:1191–1199

    Article  PubMed  CAS  Google Scholar 

  • Goel S, Hidalgo M, Perez-Soler R (2007) EGFR inhibitor-mediated apoptosis in solid tumors. J Exp Ther Oncol 6:305–320

    PubMed  CAS  Google Scholar 

  • Gopal R, Starkschall G, Tucker SL et al (2003) Effects of radiotherapy and chemotherapy on lung function in patients with non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 56(1):114–120

    Article  PubMed  Google Scholar 

  • Graham NN, Evans ML, Dahlen DD et al (1988) Drug suppression of late radiation injury in the rat lung. philadelphia: 36th annual meeting of the radiation research society, April 16–21

    Google Scholar 

  • Grdina DJ, Kataoka Y, Murley JS et al (2002) Inhibition of spontaneous metastases formation by amifostine. Int J Cancer 97:135–141

    Article  PubMed  CAS  Google Scholar 

  • Grdina DJ, Murley JS, Kataoka Y et al (2009) Amifostine induces antioxidant enzymatic activities in normal tissues and a transplantable tumor that can affect radiation response. Int J Radiat Oncol Biol Phys 73(3):886–896

    Article  PubMed  CAS  Google Scholar 

  • Greenberger JS, Epperly MW, Gretton J et al (2003) Radioprotective gene therapy. Curr Gene Ther 3:183–195

    Article  PubMed  CAS  Google Scholar 

  • Greenberger JS, Epperly MW (2007) Antioxidant gene therapeutic approaches to normal tissue radioprotection and tumor radiosensitization. In Vivo 21:141–146

    PubMed  CAS  Google Scholar 

  • Grendys EC Jr, Blessing JA, Burger R et al (2005) A phase II evaluation of flavopiridol as second-line chemotherapy of endometrial carcinoma: a Gynecologic Oncology Group Study. Gynecol Oncol 98:249–253

    Article  PubMed  CAS  Google Scholar 

  • Guo H, Epperly MW, Bernarding M et al (2003) Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) intratracheal gene therapy reduction of irradiation induced inflammatory cytokines does not protect orthotopic Lewis lung carcinomas. In Vivo 17:13–21

    PubMed  CAS  Google Scholar 

  • Haddad R, Wirth L, Costello R et al (2003) Phase II randomized study of concomitant chemoradiation using weekly carboplatin/paclitaxel with or without daily subcutaneous amifostine in patients with newly diagnosed locally advanced squamous cell carcinoma of the head and neck. Semin Oncol 30(6 suppl 18):84–88

    Article  PubMed  CAS  Google Scholar 

  • Haimovitz-Friedman A, Vlodavsky I, Chaudhuri A et al (1991) Autocrine effects of fibroblast growth factor in repair of radiation damage in endothelial cells. Cancer Res 51:2552–2558

    PubMed  CAS  Google Scholar 

  • Han HS, Han JY, Yu SY et al (2008) Randomized phase 2 study of subcutaneous amifostine versus epoetin-alpha given 3 times weekly during concurrent chemotherapy and hyperfractionated radiotherapy for limited-disease small cell lung cancer. Cancer 113:1623–1631

    Article  PubMed  CAS  Google Scholar 

  • Hanson W (1998) Eicosanoid-induced radioprotection and chemoprotection: laboratory studies and clinical applications. In: Bump E, Malaker K (eds) Radioprotectors: chemical, biological and clinical perspectives. CRC Press, Boca Raton, pp 197–221

    Google Scholar 

  • Hara T, Omura-Minamisawa M, Kang Y et al (2008) Flavopiridol potentiates the cytotoxic effects of radiation in radioresistant tumor cells in which p53 is mutated or Bcl-2 is overexpressed. Int J Radiat Oncol Biol Phys 71(5):1485–1495

    Article  PubMed  CAS  Google Scholar 

  • Hensley ML, Hagerty KL, Kewalramani T et al (2009) American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol 27:127–145

    Article  PubMed  CAS  Google Scholar 

  • Hunter N, Milas L (1983) Protection by S-2- (3-Aminopropylamino)- ethylphosphorothioic acid against radiation-induced leg contractures in mice. Cancer Res 43:1630–1632

    PubMed  CAS  Google Scholar 

  • Jemal A, Tiwari RC, Murray T et al (2004) Cancer statistics, 2004. CA Cancer J Clin 54:8–29

    Article  PubMed  Google Scholar 

  • Karp JE, Blackford A, Smith BD et al (2010) Clinical activity of sequential flavopiridol, cytosine arabinoside, and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia. Leuk Res 34(7):877–882

    Article  PubMed  CAS  Google Scholar 

  • Karp JE, Smith BD, Resar LS et al (2011) Phase I and pharmacokinetic study of bolus-infusion flavopiridol followed by cytosine arabinoside and mitoxantrone for acute leukemias. Blood 117(12):3302–3310

    Article  PubMed  CAS  Google Scholar 

  • Karp JE, Smith BD, Levis MJ et al (2007) Sequential flavopiridol, cytosine arabinoside, and mitoxantrone: a phase II trial in adults with poor-risk acute myelogenous leukemia. Clin Cancer Res 13:4467–4473

    Article  PubMed  CAS  Google Scholar 

  • Kavanagh BD, Khandelwal SR, Schmidt-Ullrich RK et al (2001) A phase I study of RSR13, a radiation-enhancing hemoglobin modifier: tolerance of repeated intravenous doses and correlation of pharmacokinetics with pharmacodynamics. Int J Radiat Oncol Biol Phys 49:1133–1139

    Article  PubMed  CAS  Google Scholar 

  • Kelland LR, Tonkin KS (1989) The effect of 3-aminobenzamide in the radiation response of three human cervix carcinoma xenografts. Radiother Oncol 15(4):363–369

    Article  PubMed  CAS  Google Scholar 

  • Kemp G, Rose P, Lurain J et al (1996) Amifostine preatreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities: results of a randomized control trial in patients with advanced ovarian cancer. J Clin Oncol 14:2101–2112

    PubMed  CAS  Google Scholar 

  • Kerbel RS (2004) Antiangiogenic drugs and current strategies for the treatment of lung cancer. Semin Oncol 31(1 suppl):54–60

    Article  PubMed  CAS  Google Scholar 

  • Khan K, Araki K, Wang D et al (2010) Head and neck cancer radiosensitization by the novel poly(ADP-ribose) polymerase inhibitor GPI-15427. Head Neck 32(3):381–391

    PubMed  Google Scholar 

  • Khuri FR, Wu H, Lee JJ et al (2001) Cyclooxygenase-2 overexpression is a marker of poor prognosis in stage I non-small cell lung cancer. Clin Cancer Res 7:861–867

    PubMed  CAS  Google Scholar 

  • Kim DW, Choy H (2004) Potential role for epidermal growth factor receptor inhibitors in combined-modality therapy for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 59(2 suppl):S11–S20

    Article  CAS  Google Scholar 

  • Kim JC, Saha D, Cao Q et al (2004) Enhancement of radiation effects by combined docetaxel and flavopiridol treatment in lung cancer cells. Radiother Oncol 71(2):213–221

    Article  PubMed  CAS  Google Scholar 

  • Kim KW, Moretti L, Mitchell LR et al (2009) Combined Bcl-2/mammalian target of rapamycin inhibition leads to enhanced radiosensitization via induction of apoptosis and autophagy in non-small cell lung tumor xenograft model. Clin Cancer Res 15(19):6096–6105

    Article  PubMed  CAS  Google Scholar 

  • Kishi K, Petersen S, Petersen C et al (2000) Preferential enhancement of tumor radioresponse by a cyclooxygenase-2 inhibitor. Cancer Res 60:1326–1331

    PubMed  CAS  Google Scholar 

  • Kligerman MM, Turrisi AT, Urtasan RC et al (1988) Final report on phase I trial of WR-2721 before protracted fractionated radiation therapy. Int J Radiat Oncol Biol Phys 14:1119–1122

    Article  PubMed  CAS  Google Scholar 

  • Koh WJ, Stelzer KJ, Peterson LM et al (1995) Effect of pentoxifylline on radiation-induced lung and skin toxicity in rats. Int J Radiat Oncol Biol Phys 31:71–77

    Article  PubMed  CAS  Google Scholar 

  • Komaki R, Lee JS, Milas L et al (2004a) Effects of amifostine on acute toxicity from concurrent chemotherapy and radiotherapy for inoperable non-small cell lung cancer: report of a randomized comparative trial. Int J Radiat Oncol Biol Phy 58:1369–1377

    Article  CAS  Google Scholar 

  • Komaki R, Liao Z, Milas L (2004b) Improvement strategies for molecular targeting: cyclooxygenase-2 inhibitors as radiosensitizers for non-small cell lung cancer. Semin Oncol 31(1 suppl 1):47–53

    Article  PubMed  CAS  Google Scholar 

  • Komaki R, Seiferheld W, Ettinger D et al (2002) Randomized phase II chemotherapy and radiotherapy trial for patients with locally advanced inoperable non-small-cell lung cancer: long-term follow-up of RTOG 92–04. Int J Radiat Oncol 53:548–557

    Article  CAS  Google Scholar 

  • Koukourakis MI, Kyrias G, Kakolyris S et al (2000) Subcutaneous administration of amifostine during fractionated radiotherapy: a randomized Phase II study. J Clin Oncol 18:2226–2233

    PubMed  CAS  Google Scholar 

  • Koukourakis MI, Simopoulos C, Minopoulos G et al (2003) Amifostine before chemotherapy: improved tolerance profile of the subcutaneous over the intravenous route. Clin Cancer Res 15:3288–3293

    Google Scholar 

  • Kouvaris JR, Kouloulias VE, Vlahos LJ (2007) Amifostine: the first selective-target and broad-spectrum radioprotector. Oncologist 12:738–747

    Article  PubMed  CAS  Google Scholar 

  • Kunert MP, Liard JF, Abraham DJ (1996) RSR-13, an allosteric effector of hemoglobin, increases systemic and iliac vascular resistance in rats. Am J Physiol 271:H602–H613

    PubMed  CAS  Google Scholar 

  • Kwon HC, Kim SK, Chung WK et al (2000) Effect of pentoxifylline on radiation response of non-small cell lung cancer: a phase III randomized multicenter trial. Radiother Oncol 56:175–179

    Article  PubMed  CAS  Google Scholar 

  • Lai A, Tran A, Nghiemphu PL et al (2011) Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. J Clin Oncol 29(2):142–148

    Article  PubMed  CAS  Google Scholar 

  • LeChevalier T, Arriagada R, Quoix E et al (1991) Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: first analysis of a randomized trial in 353 patients. J Natl Cancer Inst 83:417–423

    Article  CAS  Google Scholar 

  • Lee I, Biaglow JE, Lee J et al (2000) Physiological mechanisms of radiation sensitization by pentoxifylline. Anticancer Res 20(6B):4605–4609

    Google Scholar 

  • Lee TK, Stupans I (2002) Radioprotection: the non-steroidal anti-inflammatory drugs (NSAIDs) and prostaglandins. J Pharm Pharmacol 54:1435–1445

    Article  PubMed  CAS  Google Scholar 

  • Lefaix JL, Delanian S, Vozenin MC et al (1999) Striking regression of subcutaneous fibrosis induced by high doses of gamma rays using a combination of pentoxifylline and α-tocopherol: an experimental study. Int J Radiat Oncol Biol Phys 43:839–847

    Article  PubMed  CAS  Google Scholar 

  • Leong SS, Tan EH, Fong KW et al (2003) Randomized double-blind trial of combined modality treatment with or without amifostine in unresectable stage III non-small cell lung cancer. J Clin Oncol 21:1767–1774

    Article  PubMed  CAS  Google Scholar 

  • Liang K, Ang KK, Milas L et al (2003) The epidermal growth factor receptor mediates radioresistance. Int J Radiat Oncol Biol Phys 57:246–254

    Article  PubMed  CAS  Google Scholar 

  • Liao Z, Komaki R, Milas L et al (2005) A phase I clinical trial of thoracic radiotherapy and concurrent celecoxib for patients with unfavorable performance status inoperable/unresectable non-small cell lung cancer. Clin Cancer Res 11:3342–3348

    Article  PubMed  CAS  Google Scholar 

  • Lin TS, Blum KA, Fischer DB et al (2010) Flavopiridol, fludarabine, and rituximab in mantle cell lymphoma and indolent B-cell lymphoproliferative disorders. J Clin Oncol 28(3):418–423

    Article  PubMed  CAS  Google Scholar 

  • Liu SK, Coackley C, Krause M et al (2008) A novel poly(ADP-ribose) polymerase inhibitor, ABT-888, radiosensitizes malignant human cell lines under hypoxia. Radiother Oncol 88(2):258–268

    Article  PubMed  CAS  Google Scholar 

  • Lockhart SP (1990) Inhaled thiol and phosphothiol radioprotectors fail to protect the mouse lung. Radiother Oncol 19:187–191

    Article  PubMed  CAS  Google Scholar 

  • Lynch T, Patel T, Dreisbach L et al (2010) Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. J Clin Oncol 28(6):911–917

    Article  PubMed  CAS  Google Scholar 

  • Marshall J (2006) Clinical implications of the mechanism of epidermal growth factor receptor inhibitors. Cancer 107:1207–1218

    Article  PubMed  CAS  Google Scholar 

  • Marzatico F, Porta C, Moroni M et al (2000) In vitro antioxidant properties of amifostine (WR-2721, Ethyol™). Cancer Chemother Pharmacol 45:172–176

    Article  PubMed  CAS  Google Scholar 

  • Mason KA, Hunter NR, Raju U et al (2004) Flavopiridol increases therapeutic ratio of radiotherapy by preferentially enhancing tumor radioresponse. Int J Radiat Oncol Biol Phys 59(4):1181–1189

    Article  PubMed  CAS  Google Scholar 

  • McAleer MF, Duffy KT, Davidson WR et al (2006) Antisense inhibition of cyclin D1 expression is equivalent to flavopiridol for radiosensitization of zebrafish embryos. Int J Radiat Oncol Biol Phys 66(2):546–551

    Article  PubMed  CAS  Google Scholar 

  • McInnes C (2008) Progress in the evaluation of CDK inhibitors as antitumor agents. Drug Discov Today 13:875–881

    Article  PubMed  CAS  Google Scholar 

  • Mell LK, Malik R, Komaki R et al (2007) Effect of amifostine on response rates in locally advanced non-small-cell lung cancer patients treated on randomized controlled trials: a meta-analysis. Int J Radiat Oncol Biol Phys 68:111–118

    Article  PubMed  CAS  Google Scholar 

  • Michalowski AS (1994) On radiation damage to normal tissues and its treatment: II. Anti-inflammatory drugs. Acta Oncol 33:139–157

    Article  PubMed  CAS  Google Scholar 

  • Miki T, Bottaro DP, Fleming TP et al (1992) Determination of ligand-binding specificity by alternative splicing: two distinct growth factor receptors encoded by a single gene. Proc Natl Acad Sci USA 89:246–250

    Article  PubMed  CAS  Google Scholar 

  • Milas L (2001) Cyclooxygenase-2 (COX-2) enzyme inhibitors as potential enhancers of tumor radioresponse. Semin Radiat Oncol 11:290–299

    Article  PubMed  CAS  Google Scholar 

  • Milas L, Hanson WR (1995) Eicosanoids and radiation. Eur J Cancer 31A:1580–1585

    Article  PubMed  CAS  Google Scholar 

  • Milas L, Hunter N, Reid BO et al (1982) Protective effects of S-2-(3-Aminopropylamino)-ethylphosphorothioic acid against radiation damage of normal tissues and a fibrosarcoma in mice. Cancer Res 42:1888–1897

    PubMed  CAS  Google Scholar 

  • Milas L, Mason K, Hunter N et al (2000) In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody. Clin Cancer Res 6:701–708

    PubMed  CAS  Google Scholar 

  • Milas L, Mason KA, Liao Z et al (2003a) Chemoradiotherapy: emerging treatment improvement strategies. Head Neck 25:152–167

    Article  PubMed  Google Scholar 

  • Milas L, Mason K, Liao Z et al (2003b) Role of cyclooxygenase-2 (COX-2) and its inhibition in tumor biology and radiotherapy. In: Nieder C, Milas L, Ang KK (eds) Biological modification of radiation response: cytokines, growth factors and other biological targets. Springer, Berlin, pp 241–258

    Chapter  Google Scholar 

  • Milas L, Murray D, Brock WA et al (1988) Radioprotectors in tumor radiotherapy: factors and settings determining therapeutic ratio. Pharmacol Ther 30:179–187

    Article  Google Scholar 

  • Milas L, Nishiguchi I, Hunter N et al (1992) Radiation protection against early and late effects of ionizing irradiation by the prostaglandin inhibitor indomethacin. Adv Space Res 12:265–271

    Article  PubMed  CAS  Google Scholar 

  • Misirlioglu CH, Demirkasimoglu T, Kucukplakci B et al (2007) Pentoxifylline and alpha-tocopherol in prevention of radiation-induced lung toxicity in patients with lung cancer. Med Oncol 24(3):308–311

    Article  PubMed  CAS  Google Scholar 

  • Molteni A, Wolfe LF, Ward WF et al (2007) Effect of an angiotensin II receptor blocker and two angiotensin converting enzyme inhibitors on transforming growth factor-beta (TGF-beta) and alpha-actomyosin (alpha SMA), important mediators of radiation-induced pneumopathy and lung fibrosis. Curr Pharm Des 13(13):1307–1316

    Article  PubMed  CAS  Google Scholar 

  • Moretti L, Li B, Kim KW et al (2010) AT-101, a pan-Bcl-2 inhibitor, leads to radiosensitization of non-small cell lung cancer. J Thorac Oncol 5(5):680–687

    PubMed  Google Scholar 

  • Morris DG, Bramwell VH, Turcotte R et al (2006) A phase II study of flavopiridol in patients with previously untreated advanced soft tissue sarcoma. Sarcoma 2006:64374

    Article  PubMed  CAS  Google Scholar 

  • Moulder JE, Fish BL, Cohen EP (1993) Treatment of radiation nephropathy with ACE inhibitors. Int J Radiat Oncol Biol Phys 27:93–99

    Article  PubMed  CAS  Google Scholar 

  • Movsas B, Moughan J, Sarna L et al (2009) Quality of life supersedes the classic prognosticators for long-term survival in locally advanced non-small-cell lung cancer: an analysis of RTOG 9801. J Clin Oncol 27(34):5816–5822

    Article  PubMed  Google Scholar 

  • Movsas B, Scott C, Langer C et al (2005) Randomized trial of amifostine in locally advanced non–small-cell lung cancer patients receiving chemotherapy and hyperfractionated radiation: radiation therapy oncology group trial 98–01. J Clin Oncol 23:2145–2154

    Article  PubMed  CAS  Google Scholar 

  • Murray D, McBride WH (1996) Radioprotective agents. In: Kirk-Othmer Encyclopedia of Chemical Technology, 4th edn. vol 20, pp. 963–1006

    Google Scholar 

  • Mutter R, Lu B, Carbone DP et al (2009) A phase II study of celecoxib in combination with paclitaxel, carboplatin, and radiotherapy for patients with inoperable stage IIIA/B non-small cell lung cancer. Clin Cancer Res 15(6):2158–2165

    Article  PubMed  CAS  Google Scholar 

  • Nakata E, Mason KA, Hunter N et al (2004) Potentiation of tumor response to radiation or chemoradiation by selective cyclooxygenase-2 enzyme inhibitors. Int J Radiat Oncol Biol Phys 58(2):369–375

    Article  PubMed  CAS  Google Scholar 

  • Newcomb EW, Lymberis SC, Lukyanov Y et al (2006) Radiation sensitivity of GL261 murine glioma model and enhanced radiation response by flavopiridol. Cell Cycle 5(1):93–99

    Article  PubMed  CAS  Google Scholar 

  • Nieder C, Zimmermann FB, Adam M et al (2005) The role of pentoxifylline as a modifier of radiation therapy. Cancer Treat Rev 31(6):448–455

    Article  PubMed  CAS  Google Scholar 

  • O’Rourke N, Roqué I, Figuls M et al (2010) Concurrent chemoradiotherapy in non-small cell lung cancer. Cochrane Database Syst Rev 16(6):CD002140

    Google Scholar 

  • Ozturk B, Egehan I, Atavci S et al (2004) Pentoxifylline in prevention of radiation-induced lung toxicity in patients with breast and lung cancer: a double-blind randomized trial. Int J Radiat Oncol Biol Phys 58:213–219

    Article  PubMed  CAS  Google Scholar 

  • Panos RJ, Rubin JS, Aaronson SA et al (1993) Keratinocyte growth factor and hepatocyte growth factor/scatter factor are heparin-binding growth factors for alveolar type II cells in fibroblast-conditioned medium. J Clin Invest 92:969–977

    Article  PubMed  CAS  Google Scholar 

  • Petkau A (1987) Role of superoxide dismutase in modification of radiation injury. Br J Cancer 55(suppl VIII):87–95

    CAS  Google Scholar 

  • Pirker R, Pereira JR, Szczesna A et al (2009) Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet 373:1525–1531

    Article  PubMed  CAS  Google Scholar 

  • Powell C, Mikropoulos C, Kaye SB et al (2010) Preclinical and clinical evaluation of PARP inhibitors as tumour-specific radiosensitisers. Cancer Treat Rev 36(7):566–575

    Article  PubMed  CAS  Google Scholar 

  • Praetorius NP, Mandal TK (2008) Alternate delivery route for amifostine as a radio-/chemo-protecting agent. J Pharm Pharmacol 60:809–815

    Article  PubMed  CAS  Google Scholar 

  • Raben D, Helfrich B, Bunn PA Jr (2004) Targeted therapies for non-small-cell lung cancer: biology, rationale, and preclinical results from a radiation oncology perspective. Int J Radiat Oncol Biol Phys 59(2 Suppl):S27–S38

    Article  CAS  Google Scholar 

  • Raben D, Helfrich B, Chan DC et al (2005) The effects of cetuximab alone and in combination with radiation and/or chemotherapy in lung cancer. Clin Cancer Res 11:795–805

    PubMed  CAS  Google Scholar 

  • Raju U, Ariga H, Koto M et al (2006) Improvement of esophageal adenocarcinoma cell and xenograft responses to radiation by targeting cyclin-dependent kinases. Radiother Oncol 80(2):185–191

    Article  PubMed  CAS  Google Scholar 

  • Raju U, Nakata E, Mason KA et al (2003) Flavopiridol, a cyclin-dependent kinase inhibitor, enhances radiosensitivity of ovarian carcinoma cells. Cancer Res 63(12):3263–3267

    PubMed  CAS  Google Scholar 

  • Rasey JS, Grunbaum Z, Krohn KA et al (1985) Biodistribution of the radioprotective drug 35S-labeled 3-amino-2-hydroxypropyl phosphorothioate (WR77913). Radiat Res 102:130–137

    Article  PubMed  CAS  Google Scholar 

  • Rasey JS, Krohn KA, Menard TW et al (1986) Comparative biodistribution and radioprotection studies with three radioprotective drugs in mouse tumors. Intl J Radiat Oncol Biol Phys 12:1487–1490

    Article  CAS  Google Scholar 

  • Rathkopf D, Dickson MA, Feldman DR et al (2009) Phase I study of flavopiridol with oxaliplatin and fluorouracil/leucovorin in advanced solid tumors. Clin Cancer Res 15(23):7405–7411

    Article  PubMed  CAS  Google Scholar 

  • Redlich CA, Gao X, Rockwell S et al (1996) IL-11 enhances survival and decreases TNF production after radiation-induced thoracic injury. J Immunol 157:1705–1710

    PubMed  CAS  Google Scholar 

  • Robert F, Blumenschein G, Herbst RS et al (2005) Phase I/IIa study of cetuximab with gemcitabine plus carboplatin in patients with chemotherapy-naive advanced non-small-cell lung cancer. J Clin Oncol 23:9089–9096

    Article  PubMed  CAS  Google Scholar 

  • Roberts NA, Robinson PA (1995) Copper chelates of anti-rheumatic and anti-inflammatory agents and their superoxide dismutase-like activity and stability. Br J Rheumatol 24:128–136

    Article  Google Scholar 

  • Rosell R, Robinet G, Szczesna A et al (2008) Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer. Ann Oncol 19:362–369

    Article  PubMed  CAS  Google Scholar 

  • Rube CE, Wilfert F, Uthe D et al (2002) Modulation of radiation-induced tumour necrosis factor alpha (TNF-alpha) expression in the lung tissue by pentoxifylline. Radiother Oncol 64:177–187

    Article  PubMed  CAS  Google Scholar 

  • Rubin JS, Osada H, Finch PW et al (1989) Purification and characterization of a newly identified growth factor specific for epithelial cells. Proc Natl Acad Sci USA 86(3):802–806

    Article  PubMed  CAS  Google Scholar 

  • Russo AL, Kwon HC, Burgan WE et al (2009) In vitro and in vivo radiosensitization of glioblastoma cells by the poly (ADP-ribose) polymerase inhibitor E7016. Clin Cancer Res 15(2):607–612

    Article  PubMed  CAS  Google Scholar 

  • Saleh MN, Raisch KP, Stackhouse MA et al (1999) Combined modality therapy of A431 human epidermoid cancer using anti-EGFr antibody C225 and radiation. Cancer Biother Radiopharm 14:451–463

    Article  PubMed  CAS  Google Scholar 

  • Sarna L, Swann S, Langer C et al (2008) Clinically meaningful differences in patient-reported outcomes with amifostine in combination with chemoradiation for locally advanced non-small-cell lung cancer: an analysis of RTOG 9801. Int J Radiat Oncol Biol Phys 72:1378–1384

    Article  PubMed  Google Scholar 

  • Sasse AD, Clark LG, Sasse EC et al (2006) Amifostine reduces side effects and improves complete response rate during radiotherapy: results of a meta-analysis. Int J Radiat Oncol Biol Phys 64:784–791

    Article  PubMed  CAS  Google Scholar 

  • Sato S, Kajiyama Y, Sugano M et al (2004) Flavopiridol as a radio-sensitizer for esophageal cancer cell lines. Dis Esophagus 17(4):338–344

    Article  PubMed  CAS  Google Scholar 

  • Savoye C, Swenberg C, Hugot S (1997) Thiol WR-1065 and disulphide WR-33278, two metabolities of the drug ethyol (WR-2721), protect DNA against fast neutron-induced strand breakage. Int J Radiat Biol 71:193–202

    Article  PubMed  CAS  Google Scholar 

  • Schaake-Konig C, van den Bogaert W, Dalesio O et al (1992) Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. N Engl J Med 326:524–530

    Article  Google Scholar 

  • Schuchter LM, Glick J (1993) The current status of WR-2721 (amifostine): a chemotherapy and radiation therapy protector. J Clin Oncol 14:3112–3120

    Google Scholar 

  • Scott C, Suh J, Stea B et al (2007) Improved survival, quality of life, and quality-adjusted survival in breast cancer patients treated with efaproxiral (Efaproxyn) plus whole-brain radiation therapy for brain metastases. Am J Clin Oncol 6:580–587

    Article  CAS  Google Scholar 

  • Senzer N (2002) A phase III randomized evaluation of amifostine in stage IIIA/IIIB non-small cell lung cancer patients receiving concurrent carboplatin, paclitaxel, and radiation therapy followed by gemcitabine and cisplatin intensification: preliminary findings. Semin Oncol 29:38–41

    Article  PubMed  CAS  Google Scholar 

  • Shaw LM, Bonner H, Lieberman R (1999) Pharmacokinetic profile of amifostine. Semin Oncol 23:18–22

    Google Scholar 

  • Shaw E, Scott C, Suh J et al (2003) RSR13 plus cranial radiation therapy in patients with brain metastases: comparison with the radiation therapy oncology group recursive partitioning analysis brain metastases database. J Clin Oncol 21:2364–2371

    Article  PubMed  CAS  Google Scholar 

  • Shepherd FA, Rodrigues Pereira J, Ciuleanu T et al (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353:123–132

    Article  PubMed  CAS  Google Scholar 

  • Socinski MA, Morris DE, Halle JS et al (2004) Induction and concurrent chemotherapy with high-dose thoracic conformal radiation therapy in unresectable stage IIIA and IIIB non-small-cell lung cancer: a dose-escalation phase-I trial. J Clin Oncol 22:4341–4350

    Article  PubMed  CAS  Google Scholar 

  • Steinauer KK, Gibbs I, Ning S et al (2000) Radiation induces upregulation of cyclooxygenase-2 protein in PC-3 cells. Int J Radiat Oncol Biol Phys 48:325–328

    Article  PubMed  CAS  Google Scholar 

  • Suh JH (2004) Efaproxiral: a novel radiation sensitiser. Expert Opin Investig Drugs 13:543–550

    Article  PubMed  CAS  Google Scholar 

  • Suh JH, Stea B, Nabid A et al (2006) Phase III study of efaproxiral as an adjunct to whole-brain radiation therapy for brain metastases. J Clin Oncol 24(1):106–114

    Article  PubMed  CAS  Google Scholar 

  • Sumitomo M, Asano T, Asakuma J et al (2004) ZD1839 modulates paclitaxel response in renal cancer by blocking paclitaxel-induced activation of the epidermal growth factor receptor-extracellular signal-regulated kinase pathway. Clin Cancer Res 10:794–801

    Article  PubMed  CAS  Google Scholar 

  • Tee PG, Travis EL (1995) Basic fibroblast growth factor does not protect against classical radiation pneumonitis in two strains of mice. Cancer Res 55:298–302

    PubMed  CAS  Google Scholar 

  • Terry NHA, Brinkely J, Doig AJ et al (2004) Cellular kinetics of murine lung: model system to determine basis for radioprotection with keratinocyte growth factor. Int J Radiat Oncol Biol Phys 58:435–444

    Article  PubMed  CAS  Google Scholar 

  • Thienelt CD, Bunn PA Jr, Hanna N et al (2005) Multicenter phase I/II study of cetuximab with paclitaxel and carboplatin in untreated patients with stage IV non-small-cell lung cancer. J Clin Oncol 23:8786–8793

    Article  PubMed  Google Scholar 

  • Travis E (1984) The oxygen dependence of protection by aminothiols: implications for normal tissues and solid tumors. Int J Radiat Oncol Biol Phys 10:1495–1501

    Article  PubMed  CAS  Google Scholar 

  • Travis EL, Thames HD Jr, Tucker SL et al (1985) Late functional and biochemical changes in mouse lung after irradiation: differential effects of WR-2721. Rad Res 103:219–231

    Article  CAS  Google Scholar 

  • Turrisi AT, Kim K, Blum R et al (1999) Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 340:265–271

    Article  PubMed  CAS  Google Scholar 

  • Ulich TR, Yi ES, Longmuir K et al (1994) Keratinocyte growth factor is a growth factor for type II pneumocytes in vivo. J Clin Invest 93:1298–1306

    Article  PubMed  CAS  Google Scholar 

  • Utley JF, Seaver N, Newton GL et al (1984) Pharmacokinetics of WR-1065 in mouse tissue following treatment with WR-2721. Int J Radiat Oncol Biol Phys 10:1525–1528

    Article  PubMed  CAS  Google Scholar 

  • Viani GA, Manta GB, Fonseca EC et al (2009) Whole brain radiotherapy with radiosensitizer for brain metastases. J Exp Clin Cancer Res 28:1

    Article  PubMed  Google Scholar 

  • Vujaskovic Z, Feng Q, Rabbani ZN et al (2002a) Assessment of the protective effect of amifostine on radiation-induced pulmonary toxicity. Exp Lung Res 28:577–590

    Article  PubMed  CAS  Google Scholar 

  • Vujaskovic Z, Feng Q, Rabbani ZN et al (2002b) Radioprotection of lungs by amifostine is associated with reduction in profibrogenic cytokine activity. Radiat Res 157:656–660

    Article  PubMed  CAS  Google Scholar 

  • Wang LW, Fu XL, Clough R et al (2000) Can angiotension-converting enzyme inhibitors protect against symptomatic radiation pneumonitis? Radiat Res 153:405–410

    Article  PubMed  CAS  Google Scholar 

  • Wang R, Kagan R, Tome M (2004) Subcutaneous amifostine during radiation or chemoradiation for the treatment of head and neck cancers. ASCO Annual Meeting Proceedings. J Clin Oncol 22(14S):8154

    Google Scholar 

  • Ward HE, Kemsley L, Davies L et al (1992a) The effect of steroids on radiation-induced lung disease in the rat. Radiat Res 136:22–28

    Article  Google Scholar 

  • Ward WF, Kim YT, Molteni A et al (1988) Radiation-induced pulmonary endothelial dysfunction in rats: modification by an inhibitor of angiotensin converting enzyme. Int J Radiat Oncol Biol Phys 15:135–140

    Article  PubMed  CAS  Google Scholar 

  • Ward WF, Kim YT, Molteni A et al (1992b) Pentoxifylline does not spare acute radiation reactions in rat lung and skin. Radiat Res 129:107–111

    Article  PubMed  CAS  Google Scholar 

  • Ward WF, Lin PP, Wong PS et al (1993) Radiation pneumonitis in rats and its modification by the angiotension-converting enzyme inhibitor captopril evaluated by high resolution computer tomography. Radiat Res 135:81–87

    Article  PubMed  CAS  Google Scholar 

  • Ward WF, Molteni A, Ts’ao C et al (1990a) Captopril reduces collagen and mast cell accumulation in irradiated rat lung. Int J Radiat Oncol Biol Phys 19:1405–1409

    Article  PubMed  CAS  Google Scholar 

  • Ward WF, Molteni A, Ts’ao C et al (1990b) The effect of captopril on benign and malignant reactions in irradiated rat skin. Br J Radiol 63:349–354

    Article  PubMed  CAS  Google Scholar 

  • Ward WF, Molteni A, Ts’ao C et al (1992c) Radiation pneumotoxicity in rats: modification by inhibitors of angiotensin converting enzyme. Int J Radiat Oncol Biol Phys 22:623–625

    Article  PubMed  CAS  Google Scholar 

  • Wasserman TH, Phillips TL, Ross G et al (1981) Differential protection against cytotoxic chemotherapeutic effects on bone marrow CFUs by WR-2721. Cancer Clin Trials 4:3–6

    PubMed  CAS  Google Scholar 

  • Weiss JF, Landauer MR (2009) History and development of radiation-protection agents. Int J Radiat Biol 85:539–573

    Article  PubMed  CAS  Google Scholar 

  • Willett CG, Duda DG, Ancukiewicz M et al (2010) A safety and survival analysis of neoadjuvant bevacizumab with standard chemoradiation in a phase I/II study compared with standard chemoradiation in locally advanced rectal cancer. Oncologist 15(8):845–851

    Article  PubMed  CAS  Google Scholar 

  • Yarom R, Harper IS, Wynchangk, et al (1993) Effect of captopril on changes in rat’s hearts induced by long-term irradiation. Radiat Res 133:187–197

    Article  PubMed  CAS  Google Scholar 

  • Yi ES, Williams ST, Lee H et al (1996) Keratinocyte growth factor ameliorates radiation- and bleomycin-induced lung injury and mortality. Am J Pathol 149:1963–1970

    PubMed  CAS  Google Scholar 

  • Yoon S, Park J, Jang H et al (1994) Radioprotective effect of captopril on the mouse jejunal mucosa. Int J Radiat Oncol Biol Phys 30:873–878

    Article  PubMed  CAS  Google Scholar 

  • Yuhas JM (1980) Active versus passive absorption kinetics as the basis for selective protection of normal tissues by S-2-(3-Aminopropylamino) -ethylphosphorothioic acid. Cancer Res 40:1519–1524

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ritsuko Komaki .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Komaki, R., Liao, Z., Cox, J.D., Mason, K.A., Milas, L. (2011). Radioprotectors and Chemoprotectors in the Management of Lung Cancer. In: Jeremic, B. (eds) Advances in Radiation Oncology in Lung Cancer. Medical Radiology(). Springer, Berlin, Heidelberg. https://doi.org/10.1007/174_2011_288

Download citation

  • DOI: https://doi.org/10.1007/174_2011_288

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-19924-0

  • Online ISBN: 978-3-642-19925-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics