Chemotherapy Treatment Options for Non-small-cell Lung Cancer

Chemotherapy Treatment Options for Non-small-cell Lung Cancer

Giuseppe Altavilla, Maria Carmela Santarpia, Miguel Taron, Rafael Rosell
European Oncology Review 2005
Published: October 2008
download article

| More
dots

Cisplatin-based chemotherapy trials demonstrate a benefit for cisplatin over supportive care alone with a hazard ratio (HR) of 0.73, which translates to a 27% reduction in the risk of death and a 10% improvement in survival at one year.1 Between 1993 and 1999, 1,436 patients with stage IV or IIIB non-small-cell lung cancer (NSCLC) with effusion were treated with platinum-based doublets (involving either paclitaxel, docetaxel, vinorelbine or gemcitabine). The response rates and median survival times were 20% and 8.2 months. One- and two-year survivals were 33% and 11%, respectively.2–4 In a multivariate analysis, lower performance status (PS) – PS 1 versus 0 – was identified as one prognostic factor.2 The salient finding of the Eastern Cooperative Oncology Group (ECOG) trial4 was that no survival differences were observed between any of the different platinum-based doublets, with a modest benefit for chemotherapy in NSCLC. However, reality shows that survival can vary significantly between individual patients with some surviving years and others succumbing to their disease within a few months.4

Cisplatin-based chemotherapy trials demonstrate a benefit for cisplatin over supportive care alone with a hazard ratio (HR) of 0.73, which translates to a 27% reduction in the risk of death and a 10% improvement in survival at one year.1 Between 1993 and 1999, 1,436 patients with stage IV or IIIB non-small-cell lung cancer (NSCLC) with effusion were treated with platinum-based doublets (involving either paclitaxel, docetaxel, vinorelbine or gemcitabine). The response rates and median survival times were 20% and 8.2 months. One- and two-year survivals were 33% and 11%, respectively.2–4 In a multivariate analysis, lower performance status (PS) – PS 1 versus 0 – was identified as one prognostic factor.2 The salient finding of the Eastern Cooperative Oncology Group (ECOG) trial4 was that no survival differences were observed between any of the different platinum-based doublets, with a modest benefit for chemotherapy in NSCLC. However, reality shows that survival can vary significantly between individual patients with some surviving years and others succumbing to their disease within a few months.4 Patients with lower DNA repair capacity are more chemosensitive than those who carry a proficient DNA repair system.5–7 More recent results with docetaxel 75mg/m2 and cisplatin 75mg/m2 yielded a response rate of 31%, with a median survival of 11 months.8 A metaanalysis of randomised clinical trials comparing cisplatin with carboplatin disclosed that cisplatin doublets yielded 11% longer survival than carboplatin doublets (HR=1.1; p=0.03).9 The European Organization for Research and Treatment of Cancer (EORTC) compared cisplatin plus teniposide versus cisplatin plus paclitaxel; response rates were significantly in favour of the paclitaxel combination although there were no differences in median survival.10 Based on this study, the EORTC compared paclitaxel plus cisplatin versus paclitaxel plus gemcitabine versus gemcitabine plus cisplatin. Although there were no differences in outcomes, there was a tendency towards lower survival in the non-cisplatin arm.11 A Greek study compared docetaxel plus cisplatin versus docetaxel plus gemcitabine; both arms were supported with the use of recombinant human granulocyte colony-stimulating factor, because the dose of docetaxel was 100mg/m2. No differences in response or survival were observed.12 Recent studies of gemcitabine plus docetaxel versus vinorelbine plus cisplatin also show similar outcomes for the two regimens in terms of response and median survival.13,14 Along the same lines, a new meta-analysis has found that there are no differences in survival between platinum regimens and third-generation-based non-platinum regimens. One-year survival was 36% for platinum regimens and 35% for non-platinum regimens.15 At the 2005 ASCO meeting, a phase III trial comparing gemcitabine plus carboplatin versus gemcitabine plus paclitaxel versus paclitaxel plus carboplatin showed similar outcomes for the three regimens, with an overall time to progression of five months, a median survival of eight months, a one-year survival of 33% and a two-year survival of 10%.16

123next ›last »
References:
  1. Non-small cell lung cancer collaborative group, "Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials", BMJ (1995);311: pp. 899-909.
  2. Hoang T, Xu Ronghui, Schiller J H, et al., "Clinical model to predict survival in chemonaive patients with advanced nonsmall- cell lung cancer treated with third-generation chemotherapy regimens based on Eastern Cooperative Oncology Group data", J. Clin. Oncol. (2005);23: pp. 175-183.
  3. Kelly K, Crowley J, Bunn P, et al., "Randomized Phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small-cell lung cancer: A Southwest Oncology Group trial", J. Clin. Oncol. (2001);19: pp. 3,210-3,218.
  4. Schiller J, Harrington D, Belani C, et al., "Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer", N. Engl. J. Med. (2002);346: pp. 92-98.
  5. Rosell R, Taron M, Camps C, et al., "Influence of genetic markers on survival in non-small cell lung cancer", Drugs of Today (2003);39: pp. 775-786.
  6. Rosell R, Taron M, Barnadas A, et al., "Nucleotide excision repair pathways involved in cisplatin resistance in non-smallcell lung cancer", Cancer Control (2003);10: pp. 297-305.
  7. Rosell R, Taron M, Alberola V, et al., "Genetic testing for chemotherapy in non-small cell lung cancer", Lung Cancer (2003);41: pp. S97-S102.
  8. Fossella F, Pereira J, von Pawel J, et al., "Randomized, multinational, Phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: The TAX 326 study group", J. Clin. Oncol. (2003);21: pp. 3,016-3,024.
  9. Hotta K, Matsuo K, Ueoka H, et al., "Meta-analysis of randomized clinical trials comparing cisplatin to carboplatin in patients with advanced non-small-cell lung cancer", J. Clin. Oncol. (2004);22: pp. 3,852-3,859.
  10. Giaccone G, Splinter T, Debruyne C, et al., "Randomized study of paclitaxel-cisplatin versus cisplatin-teniposide in patients with advanced non-small-cell lung cancer", J. Clin. Oncol. (1998);16: pp. 2,133-2,141.
  11. mit E F, van Meerbeeck J, Lianes P, et al., "Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer: A phase III trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group- EORTC 08975", J. Clin. Oncol. (2003);21: pp. 3,909-3,917.
  12. Georgoulias V, Papadakis E, Alexopoulos, et al., "Platinum-based and non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a randomized multicentrre trial", Lancet (2001);357: pp. 1,478-1,483.
  13. Georgoulias V, Ardavanis A, Tsiafaki X, et al., "Vinorelbine plus cisplatin versus docetaxel plus gemcitabine in advanced non-small-cell lung cancer: A phase III randomized trial", J. Clin. Oncol. (2005);23: pp. 2,937-2,945.
  14. Pujol J L, Breton J L, Gervais R, et al., "Gemcitabine-docetaxel versus cisplatin-vinorelbine in advanced or metastatic nonsmall- cell lung cancer: a phase III study addressing the case for cisplatin", Ann. Oncol. (2005);16: pp. 602-610.
  15. D Addario G, Pintilie M, Leighl N, et al., "Platinum-based versus non-platinum-based chemotherapy in advanced nonsmall- cell lung cancer: A meta-analysis of the published literature", J. Clin. Oncol. (2005);23: pp. 2,926-2,936.
  16. Treat J, Belani C, Edelman M, et al., "A randomized phase III trial of gemcitabine (G) in combination with carboplatin (C) or paclitaxel (P) versus paclitaxel plus carboplatin in advanced (Stage IIIB, IV) non-small-cell lung cancer (NSCLC): Update of the Alpha Oncology trial", J. Clin. Oncol. (2005);ASCO Annual Meeting Proceedings; (abstr LBA7025): 627s.
  17. Zeng-Rong N, Paterson J, Alpert L, et al., "Elevated DNA repair capacity is associated with intrinsic resistance of lung cancer to chemotherapy", Cancer Res. (1995);55: pp. 4,760-4,764.
  18. Van de Vaart P J M, Belderbos J, De Jong D, et al., "DNA-adduct levels as a predictor of outcome for NSCLC patients receiving daily cisplatin and radiotherapy", Int. J. Cancer (2000);89: pp. 160-166.
  19. Bosken C, Wei Q, Amos C, et al., "An analysis of DNA repair as a determinant of survival in patients with non-smallcell lung cancer", J. Natl Cancer Inst. (2002);94: pp. 1,091-1,099.
  20. Ferry K V, Hamilton T C and Johnson S W, "Increased nucleotide excision repair in cisplatin resistant ovarian cancer cells", Biochem. Pharmacol. (2000);60: pp. 1,305-1,313.
  21. Dabholkar M, Vionnet J, Bostick-Bruton F, et al., "Messenger RNA levels of XPAC and ERCC1 in ovarian cancer tissue correlate with response to platinum-based chemotherapy", J. Clin. Invest. (1994);94: pp. 703-708.
  22. Metzger R, Leichman C G, Danenberg K, et al., "ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy", J. Clin. Oncol. (1998);16: pp. 309-316.
  23. Shirota Y, Stoehlmacher J, Brabender J, et al., "ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy", J. Clin. Oncol. (2001);19: pp. 4,298-4,304.
  24. Lord R V N, 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: pp. 2,286-2,291.
  25. Rosell R, Cobo M, Isla D, et al., "ERCC1 mRNA-based randomized phase III trial of docetaxel (doc) doublets with cisplatin (cis) or gemcitabine (gem) in stage IV non-small-cell lung cancer (NSCLC) patients (p)", J. Clin. Oncol. (2005), ASCO Annual Meeting Proceedings (abstr 7002): 621s.
  26. Husain A, He G, Venkatraman E S, et al., "BRCA1 up-regulation is associated with repair-mediated resistance to cisdiamminedichloroplatinum (II)", Cancer Res. (1998);58: pp. 1,120-1,123.
  27. Quinn J E, Kennedy R D, Mullan P B, et al., "BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis", Cancer Res. (2003);63: pp. 6,221-6,228.
  28. Tassone P, Tagliaferri P, Perricelli A, et al., "BRCA1 expression modulates chemosensitivity of BRCA1-defective HCC1937 human breast cancer cells", BJC (2003);88: pp. 1,285-1,291.
  29. Fedier A, Steiner R A, Schwarz V A, et al., "The effect of loss of Brca1 on the sensitivity to anticancer agents in p53- deficient cells", Int. J. Oncol. (2003);22: pp. 1,169-1,173.
  30. Turner N, Tutt A and Ashworth A, "Hallmarks of "BRCAness" in sporadic cancers", Nat. Rev. Cancer (2004);4: pp. 1-6.
  31. Farmer H, McCabe N, Lord C J, et al., "Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy", Nature (2005);434: pp. 917-921.
  32. Taron M, Rosell R, Felip E, et al., "BRCA mRNA expression levels as an indicator of chemoresistance in lung cancer",Hum. Mol. Genet. (2004);13: pp. 2,443-2,449.
  33. Rosell R, Danenberg K D, Alberola V, et al., "Ribonucleotide reductase messenger RNA expression and survival in gemcitabine/cisplatin-treated advanced non-small-cell lung cancer patients", Clin. Cancer Res. (2004);10: pp. 1,318-1,325.
  34. Smith I E, O Brien M, Talbot D E, et al., "Duration of chemotherapy in advanced non-small-cell lung cancer: a randomized trial of three versus six courses of mitomycin, vinblastine and cisplatin", J. Clin. Oncol. (2001);19: pp. 1,336-1,343.
  35. Belani C P, Barstis J, Perry M C, et al., "Multicenter, randomized trial for stage IIIB or IV non-small-cell lung cancer using weekly paclitaxel and carboplatin followed by maintenance weekly paclitaxel or observation", J. Clin. Oncol. (2003); 21: pp. 2,933-2,939.
  36. Westeel V, Quoix E, Moro-Sibilot D, et al., "Randomized study of maintenance vinorelbine in responders with advanced non-small-cell lung cancer", J. Natl. Cancer Inst. (2005);97: pp. 499-506.
  37. Gandara D R, Chansky K, Albain K, et al., "Consolidation docetaxel after concurrent chemoradiotherapy in stage IIIB non-small-cell lung cancer: Phase II Southwest Oncology Group Study S9504", J. Clin. Oncol. (2003);21: pp. 2,004-2,010.
  38. Gandara D R, Chansky K, Gaspar L E, Albain K S, Lara P N, Crowley J, "Long term survival in stage IIIb nonsmall- cell lung cancer (NSCLC) treated with consolidation docetaxel following concurrent chemoradiotherapy (SWOG S9504)", J. Clin. Oncol. (2005), ASCO Annual Meeting Proceedings (abstr 7059): 635s.
  39. Schiller J H, Fidias P, Dakhil S R, et al., "A phase III study of induction therapy with gemcitabine + carboplatin (GC) followed by either delayed vs. immediate second-line therapy with docetaxel (D) in advanced non-small-cell lung cancer (NSCLC): a preliminary report of induction gemcitabine + carboplatin", J. Clin. Oncol. (2005); ASCO Annual Meeting Proceedings (abstr 7142): 655s.
  40. Li Q, Gardner K, Zhang L, et al., "Cisplatin induction of ERCC1 mRNA expression in A2780/CP70 human ovarian cancer cells", J. Biol. Chem. (1998);273: pp. 23,419-23,425.
  41. Schneider S, Uchida K, Brabender J, et al., "Downregulation of TS, DPD, ERCC1, GST-Pi, EGFR, and HER2 gne expression after neoadjuvant three-modality treatment in patients with esophageal cancer", J. Am. Coll. Surg. (2005);200: pp. 336-344.
  42. Rosell R, Felip E, Taron M, et al., "Gene expression as a predictive marker of outcome in stage IIIB-IIIA-IIIB non-small cell lung cancer after induction gemcitabine-based chemotherapy followed by resectional surgery", Clin. Cancer Res. (2004); (suppl); 10: pp. 4,215s-4,219s.
  43. Weber F, Fukino K, Sawada T, et al., "Variability in organ-specific EGFR mutational spectra in tumour epithelium and stroma may be the biological basis for differential responses to tyrosine kinase inhibitors", BJC (2005);92: pp. 1,992-1,926.
  44. Tokumo M, Toyooka S, Kiura K, et al., "The relationship between epidermal growth factor receptor mutations and clinic opathologic features in non-small-cell lung cancers", Clin. Cancer Res. (2005);11: pp. 1,167-1,173.
  45. Mitsudomi T, Kosaka T, Endoh H, et al., "Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence", J. Clin. Oncol. (2005); 23: pp. 2,513-2,520.
  46. Chou T Y, Chiu C-H, Li L-H, et al., "Mutation in the tyrosine kinase domain of epidermal growth factor receptor is a predictive and prognostic factor for gefitinib treatment in patients with non-small-cell lung cancer", Clin. Cancer Res. (2005);11: pp. 3,750-3,757.
  47. Taron M, Ichinose Y, Rosell R, et al., "Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas", Clin. Cancer Res. (2005);(in press).
  48. Cortes-Funes H, Gomez C, Rosell R, et al., "Epidermal growth factor receptor activating mutations in Spanish gefitinib-treated 5 non-small-cell lung cancer patients", Ann. Oncol. (2005);(advance access published April 25), 16: pp. 1081-1,086.

Copyright® 2004 - 2010 Business Briefings, Ltd. All rights reserved.
Touch Oncology is for informational purposes and should not be considered medical advice, diagnosis or treatement recommendations.