Skip to main content

Advertisement

Log in

Promising new agents in the treatment of non-small cell lung cancer

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

A number of new drugs and drug classes have recently become available for clinical testing which demonstrate significant antitumor activity in non-small cell lung cancer. The preclinical rationale, mechanism of action, toxicity profile and results of early trials of paclitaxel, docetaxel, edatrexate, CPT-11, topotecan, vinorelbine and gemcitabine in non-small cell lung cancer are reviewed.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Abbruzzese JL, Grunewald R, Weeks EA, Gravel D, et al (1991) A phase I clinical, plasma and cellular pharmacology study of gemcitabine. J Clin Oncol 9:491

    PubMed  CAS  Google Scholar 

  2. Abigerges D, Armand J, Chabot GG, Da Costa L, Fadel E, Cote C, Herait P, Gandia D (1994) Irinotecan (CPT-11) high-dose escalation using intensive high-dose loperamide to control diarrhea. J Nat Cancer Inst 86:446

    Article  PubMed  CAS  Google Scholar 

  3. Abratt R, Bezwoda W, Falkson G, Goedhals L, Hacking D, Rugg T (1994) Efficacy and safety profile of gemcitabine in non-small cell lung cancer. A phase II study. J Clin Oncol 12:1535

    PubMed  CAS  Google Scholar 

  4. Albain KS, Crowley J, LeBlanc M, Livingston R (1991) Survival determinants in extensive stage non-small cell lung cancer: the Southwest Oncology Group Experience, J Clin Oncol 9:1618

    PubMed  CAS  Google Scholar 

  5. Anazi H, Frost P, Abbruzzese JL (1992) Synergistic cytotoxicity with combined inhibition of topoisomerases I and II (Abstract 2573). Proc Amer Assoc Cancer Res 33:431

    Google Scholar 

  6. Anderson H, Lund B, Bach F, et al (1994) Single agent activity of weekly gemcitabine in advance non-small cell lung cancer: a phase II study. J Clin Oncol 12: (9): 1821

    PubMed  CAS  Google Scholar 

  7. Balbiani L, Coppola F, Blajman C, et al (1993) Navelbine (nvb) vs NVB plus cisplatin (p) in non-small cell lung cancer (NSCLC) (Abstract 1185). Proc Am Soc Clin Oncol 12:352

    Google Scholar 

  8. Bertelli P, Mantica C, Farina G, et al (1994) Treatment of non-small cell lung cancer with vinorelbine (Abstract 1218). Proc Am Soc Clin Oncol 13:362

    Google Scholar 

  9. Binet S, Fellous A, Lataste H, et al (1989) In situ analysis of the action of navelbine on various types of microtubules using immunofluorescence. Semin Oncol 16 [Suppl 4]:5–8

    PubMed  CAS  Google Scholar 

  10. Bishop JF, Taxoid in lung cancer (1994) Lung Cancer 11 [Suppl 2]: 250–1

    Article  Google Scholar 

  11. Burris HA, Rothenburg ML, Kuhn JG, et al (1992) Clinical trials with the topoisomerase I inhibitors. Semin Oncol 19:663

    PubMed  CAS  Google Scholar 

  12. Burris H, Irvin R, Kuhn J, et al (1992) A phase I clinical trial of docetaxel as a 6 hour infusion repeated every 21 days in patients with refractory solid tumors (Abstract 369). Proc Am Soc Clin Oncol 11:137

    Google Scholar 

  13. Burris H, Echardt J, Fields S, et al (1993) Phase II trials of docetaxel in patients with non-small cell lung cancer (Abstract 1116). Proc Am Soc Clin Oncol 12:335

    Google Scholar 

  14. Cabrai F, Wible L, Brenner S, et al (1983) Taxol-requiring mutant of Chinese hamster ovary cells with impaired mitotic spindle activity. J Cell Biol 97:30–39.

    Article  Google Scholar 

  15. Cerny T, Kaplan S, Pavlioli N, et al (1994) Taxotere (docetaxel) is an active drug in non-small cell lung cancer: a phase II trial of the EORTC Early Clinical Trials Group (ECTG). Br JCA 70:384

    CAS  Google Scholar 

  16. Chang A, Kim K, Glick J. et al (1993) Phase II study of paclitaxel in patients with stage IV non-small cell lung cancer (NSCLC): The Eastern Cooperative Oncology Group (ECOG) results. J Natl Cancer Inst 85:389

    Article  Google Scholar 

  17. Cormier Y, Shepherd F, Burkes R, et al (1994) Phase I study of gemcitabine (gem) and cisplatin (cp) for advanced non-small cell lung cancer (NSCLC) (Abstract 1140). Proc Am Soc Clin Oncol 13:342

    Google Scholar 

  18. Cros S, Wright M, Roussakis C, et al (1989) Experimental antitumor activity of navelbine (5’-nor-anhydrovinblastine, vinorelbine). Semin Oncol 16: (Suppl 4) 15–20

    PubMed  CAS  Google Scholar 

  19. Depierre A, Lemarie E, Dabouis G, et al (1988) Phase II study of navelbine (nvb) in non-small cell lung cancer (Abstract 778). Proc Am Soc Clin Oncol 7:201

    Google Scholar 

  20. Depierre A, Lebeau B, Chastang Cl, et al (1993) Result of a phase III randomized study of vinorelbine (v) versus vinorelbine-cis-platin (vp) in non-small cell lung cancer (NSCLC) (Abstract 1138). Proc Am Soc Clin Oncol 12:340

    Google Scholar 

  21. Diamandidis DT, Lee JS, Shin DM, et al (1994) Phase I study of taxol and edatrexate (edam) chemotherapy in solid tumors (Abstract 453). Proc Am Soc Clin Oncol 13:165

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  23. Drinkard L, Hoffman P, Bitran J, et al (1994) A phase I-II trial of navelbine (n) and ifosfamide (i) with granulocyte colony stimulating factor (G-CSF) support in advanced non-small cell lung cancer (NSCLC) (Abstract 1186). Proc Am Soc Clin Oncol 13:354

    Google Scholar 

  24. Dunlop DJ, Cameron C, Dabouis G, et al (1994) Phase I dose-escalation study of cisplatin in combination with gemcitabine in non-small cell lung cancer (Abstract 1139). Proc Am Soc Clin Oncol 13:342

    Google Scholar 

  25. Ettinger DS, Finkelstein DM, Sarma R, et al (1993) Phase II study of taxol in patients (pts) with extensive-stage small cell lung cancer (SCLC): An Eastern Cooperative Oncology Group Study (Abstract 1094). Proc Am Soc Clin Oncol 12:329

    Google Scholar 

  26. Fennelly DM, Rigas JR, Chou D, et al (1994) Phase I trial of edatrexate plus paclitaxel using an administration of schedule with demonstrated in vitro synergy (Abstract 1232). Proc Am Soc Clin Oncol 13:365

    Google Scholar 

  27. Forastiere, AA, Rowinsky E, Chaudry V, et al (1992) Phase I trial of paclitaxel and cisplatin + G-CSF in solid tumors (Abstract 289). Proc Am Soc Clin Oncol 11:117

    Google Scholar 

  28. Fossella FV, Lippman S, Pang A, et al (1993) Phase I/II study of gemcitabine (g) by 30 minute weekly intravenous (iv) infusion x 3 wks every 4 wks for non-small cell lung cancer (NSCLC) (Abstract 1082). Proc Am Soc Clin Oncol 12:326

    Google Scholar 

  29. Fossella FV, Lee JS, Murphy WK, et al (1994) Phase II study of docetaxel for recurrent or metastatic non-small cell lung cancer. J Clin Oncol 12:1238

    PubMed  CAS  Google Scholar 

  30. Fossella FV, Lee JS, Shin DM, et al (1995) Phase II study of docetaxel for advanced or metastatic platinum-refractory non-small cell lung cancer. J Clin Oncol 13: (3): 645–651

    PubMed  CAS  Google Scholar 

  31. Francis PA, Rigas JR, Kris MG, et al (1994) Phase II trial of docetaxel in patients with stage III and IV non-small cell lung cancer. J Clin Oncol 12:1232

    PubMed  CAS  Google Scholar 

  32. Fukuoka M, Niitani H, Suzuki A, et al (1992) A phase II study of CPT-11, a new derivative of camptothecin, for previously untreated non-small cell lung cancer. J Clin Oncol 10:16

    PubMed  CAS  Google Scholar 

  33. Galindo E, Kavanagh J, Fossella F, et al (1994) Docetaxel (Taxotere) toxicities: analysis of a single institution experience of 168 patients (623 courses) (Abstract 452). Proc Am Soc Clin Oncol 13:164

    Google Scholar 

  34. Gandara DR, Perez EA, Edelman MS et al (1995) Phase I trial of (edatrexate) plus carboplatin in advanced solid tumors: amelioration of dose limiting mucosites by ice-chip cryotherapy (Abstract 1513). Proc Am Soc Clin Oncol 14:468

    Google Scholar 

  35. Grever MR, Schepartz SA, Chabner BA (1992) The National Cancer Institute: cancer drug discovery and development program. Semin Oncol 19:622

    PubMed  CAS  Google Scholar 

  36. Horwitz SB, Cohen D, Rao S, et al (1993) Taxol: mechanisms of action and resistance. J Natl Cancer Inst 15:55–61

    Google Scholar 

  37. Ihde DC (1991) Chemotherapy combined with chest irradiation for locally advanced non-small cell lung cancer. Ann Intern Med 115:737

    PubMed  CAS  Google Scholar 

  38. Israel VK, Zaretsky S, Natale RB (1994) Phase I/II trial of combination carboplatin and taxol in advanced non-small cell lung cancer (NSCLC) (Abstract 1175). Proc Am Soc Clin Oncol 13:351

    Google Scholar 

  39. Kaye SB (1994) Gemcitabine: current status of phase I and II trials. J Clin Oncol 12:1527

    PubMed  CAS  Google Scholar 

  40. Kim JH, Kim SH, Kolozsvary A, et al (1992) Potentiation of radiation response in human carcinoma cells in vitro and murine fibrosarcoma in vivo by topotecan, an inhibitor of DNA topoisomerase I. Int J Rad Oncol Biol Phys 22:515

    CAS  Google Scholar 

  41. Klastersky J, Sculier JP (1994) Paclitaxel (p) plus cisplatin (c) in non-small cell lung cancer: a dose finding study (Abstract 1169). Proc Am Soc Clin Oncol 13:349

    Google Scholar 

  42. Kris MG, Kinahan JJ, Gralla RJ, et al (1988) Phase I trial and clinical pharmacological evaluation of 10-ethyl-10-deazaaminopterin in adult patients with advanced cancer. Cancer Res 48:5573

    PubMed  CAS  Google Scholar 

  43. Kris MG, Gralla RJ, Potanovich LM, et al (1991) Long term survival analysis of stage III and IV non-small cell lung cancer patients treated with edatrexate (Abstract 408). Lung Cancer (Suppl)7:111

    Google Scholar 

  44. Langer CJ, Curran WJ, Catalano R, et al (1994) Long term survival results for patients with locally advanced non-small cell lung carcinoma (NSCLC) treated with aggressive concurrent chemoradiotherapy (Abstract 1102). Proc Am Soc Clin Oncol 13:333

    Google Scholar 

  45. Langer CJ, Leighton J, Comis R, et al (1994) Taxol and carboplatin (CBDCA) in combination in stage IV and IIIB non-small cell lung cancer (NSCLC): a phase II trial (Abstract 1122). Proc Am Soc Clin Oncol 13:338

    Google Scholar 

  46. Le Chevalier T, Brisgand D, Douillard JY, et al (1994) Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small cell lung cancer: results of a European multicenter trial including 612 patients. J Clin Oncol 12(2): 360

    PubMed  Google Scholar 

  47. Lee JS, Libshitz HI, Murphy WK, et al (1990) Phase II study of 10-ethyl-10-deaza-aminopterin (10-EdAM; CGP 30 694) for stage IIIB or IV non-small cell lung cancer. Investigational New Drugs 8:299

    Article  PubMed  CAS  Google Scholar 

  48. Lee JS, Libshitz HI, Murphy WK, et al (1991) Edatrexate improves the antitumor effects of cyclophosphamide and cisplatin against non-small cell lung cancer. Cancer 68:959

    Article  PubMed  CAS  Google Scholar 

  49. Lee JS, Libshitz HI, Fossella FV, et al (1992) Improved therapeutic index by leucovorin of edatrexate, cyclophosphamide and cisplatin against non-small cell lung cancer. J Natl Cancer Inst 84:1039

    Article  PubMed  CAS  Google Scholar 

  50. Lonardi F, Pavanato G, Jirillo A, et al (1994) Vinorelbine (vnb) as single-agent chemotherapy (ct) in advanced non-small cell lung cancer (NSCLC) patients (pts) (Abstract 1123). Proc Am Soc Clin Oncol 13:338

    Google Scholar 

  51. Lynch TJ, Kalish L, Strauss G, et al (1994) Phase II study of topotecan in metastatic non-small cell lung cancer. J Clin Oncol 12(2): 347

    PubMed  Google Scholar 

  52. Marantz A, Lewi D, Litovska S, et al (1994) Phase II study of vinorelbine (vn) and ifosfamide (ifx) for non-small cell lung cancer (NSCLC) (Abstract 1071). Proc Am Soc Clin Oncol 13:325

    Google Scholar 

  53. Masuda N, Fukuoka M, Takada M, et al (1992) CPT-11 in combination with cisplatin for advanced non-small cell lung cancer. J Clin Oncol 10:1775

    PubMed  CAS  Google Scholar 

  54. Masuda N, Fukuoka M, Yusunoki Y, et al (1993) Phase I study of irinotecan (CPT-11) and cisplatin (CDDP) plus G-CSF for advanced non-small cell lung cancer (NSCLC) (Abstract 1086). Proc Am Soc Clin Oncol 12:327

    Google Scholar 

  55. Masuda N, Fukuoka M, Kudoh S, et al (1994) Phase I and pharmacologic study of irinotecan and etoposide with recombinant human granulocyte colony-stimulating factor support for advanced lung cancer. J Clin Oncol 12 1833: (No. 9)

    PubMed  CAS  Google Scholar 

  56. Miller VA, Rigas JR, Kris MG, et al (1994) Phase II trial of docetaxel given at a dose of 75 mg/m2 with prednisone premedication in non-small cell lung cancer (NSCLC) (Abstract 1226). Proc Am Soc Clin Oncol 13:364

    Google Scholar 

  57. Morere JF, Brunet A, Duran A, et al (1994) Ifosfamide (ifx) and vinorelbine (nvb) in advanced non-small cell lung cancer (NSCLC) (Abstract 1149). Proc Am Soc Clin Oncol 13: 344

    Google Scholar 

  58. Mori K, Suga U, Kishiro I, et al (1994) A phase I study of CPT-11 and cisplatin (5-day continuous infusion) for advanced non-small cell lung cancer (Abstract 1234). Proc Am Soc Clin Oncol 13:366

    Google Scholar 

  59. Murphy WK, Fossella FV, Winn RJ, et al (1993) A phase II study of taxol in patients with non-small cell lung cancer. J Natl Cancer Inst 85:384

    Article  PubMed  CAS  Google Scholar 

  60. Murphy WK, Winn RJ, Huber M, et al (1994) Phase II study of taxol (t) in patients (pt) with non-small cell lung cancer (NSCLC) who have failed platinum (p) containing chemotherapy (ctx) (Abstract 1224). Proc Am Soc Clin Oncol 13:363

    Google Scholar 

  61. Nakagawa K, Fukuoka M, Niitani H, et al (1993) Phase II study of irinotecan (CPT-11) and cisplatin in patients with advanced non-small cell lung cancer (NSCLC) (Abstract 1104). Proc Am Soc Clin Oncol 12:332

    Google Scholar 

  62. Negoro S, Fukuoka M, Niitani H, et al (1991) Phase II study of CPT-11, new camptothecin derivative, in small cell lung cancer (SCLC) (Abstract 822). Proc Am Soc Clin Oncol 10:241

    Google Scholar 

  63. Paul DM, Johnson DH, Hande KR, et al (1994) Carboplatin (c) and taxol (t): A well tolerated regimen for advanced non-small cell lung cancer (NSCLC) (Abstract 1181). Proc Am Soc Clin Oncol 13:352

    Google Scholar 

  64. O’Rourke MA, Crawford J, Schiller J, et al. Survival advantage for patients with stage IV NSCLC treated with single agent navelbine in a randomized controlled trial (Abstract 1148) (1993) Proc Am Soc Clin Oncol 12: 343

    Google Scholar 

  65. Perez EA, Hack FM, Webber LM, Chou TC (1993) Schedule-dependent synergism of edatrexate and cisplatin combination in the A549 lung cancer cell line as assessed by median effect analysis. Cancer Chemother Pharmacol 33:245

    Article  PubMed  CAS  Google Scholar 

  66. Perez EA, Hack FM, Fletcher TS, Chou TC (1994) Modulation of intrinsic in vitro resistance to carboplatin by edatrexate in the A549 human non-small cell lung cancer cell line. Oncol Res 6:151

    PubMed  CAS  Google Scholar 

  67. Perez-Soler R, Glisson BS, Kane J, et al (1994) Phase II study of topotecan in patients with non-small cell lung cancer (NSCLC) previously untreated (Abstract 1223). Proc Am Soc Clin Oncol 13:363

    Google Scholar 

  68. Richards II F, White D, Muss H, et al (1994) Phase I trial of gemcitibine (21, 21-Difluorodeoxycytidine) (g) over 30 minutes in patients (pts) with non-small cell lung cancer (NSCLC) (Abstract 1147). Proc Am Soc Clin Oncol 13:344

    Google Scholar 

  69. Ringel I, Horwitz SB (1991) Studies with RP56976 (docetaxel): A semisynthetic analogue of taxol. J Natl Cancer Inst 83:288

    Article  PubMed  CAS  Google Scholar 

  70. Rowinsky EK, Donehower RC, Jones RJ, et al (1990) Taxol: a novel investigational antineoplastic agent. J Natl Cancer Inst 82:1247

    Article  PubMed  CAS  Google Scholar 

  71. Rowinsky EK, Onetto N, Canetta RM, Arbuck SG (1992) Taxol: the first of the taxanes, an important new class of antitumor agents. Semin Oncol 19:646

    PubMed  CAS  Google Scholar 

  72. Rowinsky EK, Chaudhry V, Forastiere AA, et al (1993) Phase I and pharmacologic study of taxol and cisplatin with granulocyte colony-stimulating factor: neuromuscular toxicity is dose-limiting. J Clin Oncol 11:2010

    PubMed  CAS  Google Scholar 

  73. Rowinsky E, Grochow L, Kaufman S, et al (1994) Sequence-dependent effects of topotecan (t) and cisplatin (c) in a phase I and pharmacokinetic (pk) study (Abstract 361). Proc Am Soc Clin Oncol 13:142

    Google Scholar 

  74. Saltz L, Sirott M, Young C, et al (1993) Phase I clinical and pharmacology study of topotecan given daily for 5 consecutive days to patients with advanced solid tumors, with attempt at dose intensification using recombinant greanulocyte colony-stimulating factor. J Natl Cancer Inst 85:1499

    Article  PubMed  CAS  Google Scholar 

  75. Santomaggio C, Righi R, Tucci E, et al (1994) Carboplatin (CBDCA) and vinorelbine (v) in the treatment of patients (pts) affected by advanced non-small cell lung cancer (NSCLC) (Abstract 1211). Proc Am Soc Clin Oncol 13:360

    Google Scholar 

  76. Schaake-Koning 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

    PubMed  CAS  Google Scholar 

  77. Schiff PB, Fant J, Horwitz SB (1979) Promotion of microtubule assembly in vitro by taxol. Nature 22:665

    Article  Google Scholar 

  78. Schmid FA, Sirotnak FM, Otter GM, DeGraw JI (1987) Combination chemotherapy with a new folate analog: Activity of 10-ethyl-10-deaza-aminopterin compared to methotrexate with 5-fluorouracil murine tumor models. Cancer Treat Rep 71:727

    PubMed  CAS  Google Scholar 

  79. Shepherd FA, Gatzemeier U, Gotfried M, et al (1993) An extended phase II study of gemcitabine in non-small cell lung cancer (NSCLC) (Abstract 1096). Proc Am Soc Clin Oncol 12:330

    Google Scholar 

  80. Shinkai T, Arioka H, Kunikane H, et al (1993) A phase I study of CPT-11 and cisplatin in combination with fixed dose of vindesine in metastatic non-small cell lung cancer (NSCLC) (Abstract 1089). Proc Am Soc Clin Oncol 12:328

    Google Scholar 

  81. Shum KY, Kris MG, Gralla RJ, et al (1988) Phase II study of 10-ethyl-10-deaza-aminopterin in patients with stage III and IV non-small cell lung cancer. J Clin Oncol 6:446

    PubMed  CAS  Google Scholar 

  82. Sirotnak FM, DeGraw JI, Moccio DM, Samuels LL, Goutas LJ (1984) New folate analogs of the 10-deaza-aminopterin series. Basis for structural design and biochemical pharmacological properties. Cancer Chemother and Pharmacol 12:18

    CAS  Google Scholar 

  83. Sirotnak FM, DeGraw JI, Schmidt FA, Goutas LJ, Moccio DM (1984) New folate analogs of the 10-deaza-aminopterin series. Further evidence for markedly increased antitumor efficacy compared to methotrexate in ascites and solid murine tumor models. Cancer Chemother and Pharmacol 12:26

    CAS  Google Scholar 

  84. Souhami RL, Rudd RM, Spiro SG, et al (1992) Phase II study of edatrexate in stage III and IV non-small cell lung cancer. Cancer Chemother and Pharmacol 30:465

    Article  CAS  Google Scholar 

  85. Swenerton K, Eisenhauer, Huinink W, et al (1993) Taxol in relapsed ovarian cancer: high vs low dose and short vs long infusion: A European-Canadian study coordinated by the NCI Canada clinical trials group (Abstract 810). Proc Am Soc Clin Oncol 12:256

    Google Scholar 

  86. Tomiak E, Piccart MJ, Kerger J, et al (1994) Phase I study of docetaxel administered as a 1-hour intravenous infusion on a weekly basis. J Clin Oncol 12:1458

    PubMed  CAS  Google Scholar 

  87. Vokes EE, Rosenberg RK, Jahanzeb M, et al (1995) Multicenter phase II study of weekly oral vinorelbine for stage IV non-small cell lung cancer. J Clin Oncol 13:637–644

    PubMed  CAS  Google Scholar 

  88. Watanabe K, Yokoyama A, Furuse K, et al (1994) Phase II trial of docetaxel in previously untreated non-small cell lung cancer (NSCLC) (Abstract 1095). Proc Am Soc Clin Oncol 13:331

    Google Scholar 

  89. Yokoyama A, Furuse K, Niitani H, et al (1992) Multi-institutional phase II study of navelbine (vinorelbine) in non-small cell lung cancer (Abstract 957). Proc Am Soc Clin Oncol 11: 287

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Edelman, M.J., Gandara, D.R. Promising new agents in the treatment of non-small cell lung cancer. Cancer Chemother Pharmacol 37, 385–393 (1996). https://doi.org/10.1007/s002800050402

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s002800050402

Keywords

Navigation