High-dose Chemotherapy of Small-Cell Lung Cancer With and Without Bone Marrow Transplantation

  • J. P. Sculier
  • J. Klastersky
Part of the Cancer Treatment and Research book series (CTAR, volume 45)


The administration of active combination chemotherapy has resulted in a major advance in the treatment of small-cell lung cancer (SCLC) [1,2]. Chemotherapy not only induces frequent objective response rates between 75% and 95%, but also prolongs survival significantly. However, only a minority of the patients cna be considered as cured [3–5]. The five-year overall survival rate is about 5–10% and there are 10 times more long-term survivors among patients with limited disease than in those with disseminated cancer. Various attempts have been proposed to improve these results [6]: administration of new active drugs, development of consolidation and/or maintenance treatments, use of more intensive regimens, administration of alternating or sequential combinations of chemotherapy, adjuvant thoracic irradiation and/or surgery, and/or more effective prevention of central nervous system relapses. Among these approaches, intensive chemotherapy is particularly appealing, although it may result in higher toxicity.


Clin Oncol Autologous Bone Marrow Transplantation Central Nervous System Relapse Toxic Death Intensive Regimen 
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  1. 1.
    Ianuzzi MC, Scoggin CH: Small-cell lung cancer. Am Rev Respir Dis 134:593–608, 1986.Google Scholar
  2. 2.
    Johnson DH, Greco FA: Small-cell lung cancer: current perspectives. Am J Med Sci 293:377–389, 1987.CrossRefGoogle Scholar
  3. 3.
    Livingstone RB, Stephens RL, Bonnet JD, Grozea PN, Lehane DE: Long-term survival and toxicity in small-cell lung cancer. Southwest Oncology Group Study. Am J Med 77:415–417, 1984.CrossRefGoogle Scholar
  4. 4.
    Johnson BE, Ihde DC, Bunn PA, Becker B, Walsh T, Weinstein ZR, Matthews MJ, Whang-Peng J, Makuch RN, Johnston-Early A, Lichter AS, Carney DN, Cohen MH, Glatstein E, Minna JD: Patients with small-cell lung cancer treated with combination chemotherapy with or without irradiation. Data on potential cures, chronic toxicities and late relapses after a five-to-eleven year follow-up. Ann Intern Med 103:430–438, 1985.PubMedGoogle Scholar
  5. 5.
    Soulier JP, Klastersky J, Nguyen N, Becquart D, Vandermoten G, Rocmans P, Michel J, Debusscher L, Longeval E, Mairesse M, Ravez P, Libert P, Thiriaux J, Dalesio O, Mommen P: Polychimiothérapie du cancer bronchique indifferéncé à petites cellules. Résultats à long terme. Presse Médicale 15:830–833, 1986.Google Scholar
  6. 6.
    Soulier JP, Klastersky J: Le cancer bronchique indifférencié à petites cellules. Rev Méd Brux 6:13–19, 1985.Google Scholar
  7. 7.
    Maral J, Jacquillat C: Protocoles de chimiothérapie des tumeurs solides: faut-il escalader ou réduire. Biomed Pharmacother 38:5–12, 1984.PubMedGoogle Scholar
  8. 8.
    Frei E III, Canellos GP: Dose: a critical factor in cancer chemotherapy. Am J Med 69:585–594, 1987.CrossRefGoogle Scholar
  9. 9.
    Norton L, Simon R: Tumor size, sensitivity to therapy, and design of treatment schedules. Cancer Treat Rep 61:1307–1317, 1977.PubMedGoogle Scholar
  10. 10.
    Skipper HE, Chabel FM Jr: Tumor stemcell heterogeneity: implications with respect to classification of cancers by chemotherapeutic effect. Cancer Treat Rep 68:43–61, 1984.PubMedGoogle Scholar
  11. 11.
    Tannock IF: Experimental chemotherapy and concepts related to the cell cycle. Int J Radiat Biol 49: 335–355, 1986.CrossRefGoogle Scholar
  12. 12.
    Goldie JH, Coldman AJ, Gudauskas GA: Rationale for the use of alternating non-cross-resistant chemotherapy. Cancer Treat Rep 66:439–449, 1982.PubMedGoogle Scholar
  13. 13.
    Hryniuk W, Bush H: The importance of dose intensity in chemotherapy of metastatic breast cancer. J Clin Oncol 2:1281–1288, 1984.PubMedGoogle Scholar
  14. 14.
    Hryniuk WM, Levine MN: Analysis of dose intensity for adjuvant chemotherapy trials. J Clin Oncol 4:1161–1170, 1986.Google Scholar
  15. 15.
    Schabel FM, Griswold DP, Corbett TH, Laster WR Jr: Increasing therapeutic response rates to anticancer drugs by applying the basic principles of pharmacology. Pharmacol Ther 20:283–305, 1983.PubMedCrossRefGoogle Scholar
  16. 16.
    Sculier JP, Klastersky J: Perspectives for the use of high-dose chemotherapy in the treatment of solid malignant tumors. Eur J Cancer Clin Oncol 20:1335–1337, 1984.PubMedCrossRefGoogle Scholar
  17. 17.
    Glode LM, Robinson WA, Hartmann DW, Klein JJ, Thomas MR, Morton N: Autologous bone marrow transplantation in the therapy of small cell carcinoma of the lung. Cancer Res 42:4270–4275, 1982.PubMedGoogle Scholar
  18. 18.
    Clark SS, Kamen R: The human hematopoietic colony-stimulating factors. Science 236: 1229–1237, 1987.PubMedCrossRefGoogle Scholar
  19. 19.
    Edmonson JH, Lagakos SW, Selawry OS, Perlia CP, Bennett JM, MUggia FM, Wampler G, Brodovsky HS, Horton J, Colsky J, Mansour EG, Creech R, Stolbach L, Greenspan EM, Levitt M, Israel L, Ezdinli EZ, Carbone PP: Cyclophosphamide and CCNU in the treatment of inoperable small cell carcinoma and adenocarcinoma of the lung. Cancer Treat Rep 60:925–932, 1976.PubMedGoogle Scholar
  20. 20.
    Hansen HH, Dombernowsky P, Hansen M, Hirsch F: Chemotherapy of advanced small-cell anaplastic carcinoma. Superiority of a 4 drug combination to a three drug combination. Ann Intern Med 89:177–181, 1978.PubMedGoogle Scholar
  21. 21.
    Maurer LH, Tulloh M, Weiss RB, Blom J, Leone L, Glidewell O, Pajak TF: A randomized combined modality trial in small cell carcinoma of the lung. Comparison of combination chemotherapy-radiation therapy versus cyclophosphamide-radiation therapy effects of maintenance chemotherapy and prophylactic whole brain irradiation. Cancer 45:30–39, 1980.PubMedCrossRefGoogle Scholar
  22. 22.
    Ettinger DS, Lagakos S: Phase III study of CCNU, cyclophosphamide, adriamycin, vincristine, and VP16 in small-cell carcinoma of the lung. Cancer 49:1544–1554, 1982.PubMedCrossRefGoogle Scholar
  23. 23.
    Jackson OV, Zekan PJ, Caldwell RD, Slatkoff ML, Harding RW, Case LD, Hopkins JO, Muss HB, Richards FII, White DR, Cooper MR, Stuart JJ, Capizzi RL, Spurr CL: VP-16-213 in combination chemotherapy with chest irradiation for small-cell lung cancer: a randomized trial of the Piedmont Oncology Association. J Clin Oncol 2:1343–1351, 1984.PubMedGoogle Scholar
  24. 24.
    Lowenbraun S, Birch R, Buchanan R, Krauss S, Durant J, Perez C, Mill W, Vollmer R, Ogden L, and the Southeastern Cancer Study Group: Combination chemotherapy in small cell lung carcinoma. A randomized study of two intensive regimens. Cancer 54:2344–2350, 1984.PubMedCrossRefGoogle Scholar
  25. 25.
    Zhiyi Z, Shenzhong W, Xiafang Z: Small-cell carcinoma of the lung: results of combination chemotherapy and radiation therapy (COF vs COFP randomized analyzed). Int J Radiat Oncol Biol Phys 10:2139–2143, 1984.CrossRefGoogle Scholar
  26. 26.
    Messeih AA, Schweitzer JM, Lipton A, Harvey HA, Simmonds MA, Stryker JA, Ricci JA, Hoffman SL, Gottleib RJ, Dixon RH, Shope ES, Meloy JH, Walker BK, Gordon RA, Heckard R, White DS: Additionof etoposide to cyclophosphamide, doxorubicin and vincristine for remission induction and survival in patients with small cell lung cancer. Cancer Treat Rep 71:61–66, 1987.PubMedGoogle Scholar
  27. 27.
    Cohen MH, Creaven PJ, Fossieck BE Jr, Broder LE, Selawry OS, Johnston AV, Williams CL, Minna JD: Intensive chemotherapy of small cell bronchogenic carcinoma. Cancer Treat Rep 61:349–354, 1977.PubMedGoogle Scholar
  28. 28.
    Figueredo AT, Hryniuk WM, Strautmanis I, Frank G, Rendell S: Cotrimoxazole prophylaxis during high-dose chemotherapy of small-cell lung cancer. J Clin Oncol 3:54–64, 1985.PubMedGoogle Scholar
  29. 29.
    O’Donnell MR, Ruckdeschel JC, Baxter D, McKneally MF, Caradonna R, Horton J: Intensive induction chemotherapy for small-cell anaplastic carcinoma of the lung. Cancer Treat Rep 69:571–575, 1985.PubMedGoogle Scholar
  30. 30.
    Wolff SN, Birch R, Sarma P, Greco FA: Randomized dose-response evaluation of etoposide in small-cell carcinoma of the lung: a Southeastern Cancer Study Group Trial. Cancer Treat Rep 70:583–587, 1986.PubMedGoogle Scholar
  31. 31.
    Ihde DC, Johnson BE, Mulshine JL, Sausville EA, Veach SR, Steinberg SM, Edison M, Lesar M, Minna JD: Randomized trial of high dose versus standard dose etoposide and cisplatin (VP16/Plat) in extensive stage small-cell lung cancer. Proc 23rd Meeting ASCO, Atlanta (USA), 1987, abstract no.714a.Google Scholar
  32. 32.
    Fahra P, Spitzer G, Valdivieso M, Dicke KA, Zander A, Dhingra HM, Minnhaar G, Vellekoop L, Verma DS, Umsawasdi T, Chiuten D: High-dose chemotherapy and autologous bone marrow transplantation for the treatment of small-cell lung carcinoma. Cancer 52:1351–1355, 1983.CrossRefGoogle Scholar
  33. 33.
    Souhami RL, Harper PG, Linch D, Trask C, Goldstone AH, Tobias JS, Spiro SG, Geddes DM, Richards JDM: High-dose cyclophosphamide with autologous marrow transplantation for small-cell carcinoma of the bronchus. Cancer Chemother Pharmacol 10:205–207, 1983.PubMedCrossRefGoogle Scholar
  34. 34.
    Souhami RL, Finn G, Gregory WM, Birkhead BG, Buckman R, Edwards D, Goldstone AH, Harper PG, Spiro SG, Tobbias JS, Geddes D: High-dose cyclophosphamide in small-cell carcinoma of the lung. J Clin Oncol 3:958–963, 1985.PubMedGoogle Scholar
  35. 35.
    Johnson DH, Wolff SN, Hainsworth JD, Porter LL, Grosh WW, Hande KR, Greco FA: Extensive-stage small-cell bronchogenic carcinoma: intensive induction chemotherapy with high-dose cyclophosphamide plus high-dose etoposide. J Clin Oncol 3:170–175, 1985.PubMedGoogle Scholar
  36. 36.
    Thatcher N, James RD, Steward WP, Barber PV, Feinmann D, Lawson BAM, Carroll KB: Three months’ treatment with cyclophosphamide, VP16-213 followed by methotrexate and thoracic radiotherapy for small-cell lung cancer. Cancer 56:1332–1336, 1985.PubMedCrossRefGoogle Scholar
  37. 37.
    Thatcher N, Stout R, Smith DB, Grötte G, Winson M, Bassett H, Carroll KB: Three months’ treatment with chemotherapy and radiotherapy for small-cell lung cancer. Br J Cancer 52:327–332, 1985.PubMedCrossRefGoogle Scholar
  38. 38.
    Postmus PE, Mulder NH, Devries-Hospers HG, Mulder POM, Maas A, Meinesz AF, Sleijfer DT, Devries EGE: High-dose cyclophosphamide and high-dose VP16–213 for recurrent or refractory small-cell lung cancer. A phase II study. Eur J Cancer Clin Oncol 21:1467–1470, 1985.PubMedCrossRefGoogle Scholar
  39. 39.
    Littlewood TJ, Bentley DP, Smith AP: High-dose etoposide with autologous bone marrow transplantation as initial treatment of small-cell lung cancer—a negative report. Eur J Respir Dis 68:370–374, 1986.PubMedGoogle Scholar
  40. 40.
    Johnson DH, Deleo MJ, Hande KR, Wolff SN, Hainsworth JD, Greco FA: High-dose induction chemotherapy with cyclophosphamide, etoposide and cisplatin for extensive-stage small-cell lung cancer. J Clin Oncol 5:703–709, 1987.PubMedGoogle Scholar
  41. 41.
    Luikart SD, Propert KJ, Modeas CR, Green MR, Perry MC: High-dose etoposide therapy for extensive small-cell lung cancer: a Cancer and Leukemia Group B study. Cancer Treat Rep 71:533–534, 1987.PubMedGoogle Scholar
  42. 42.
    Klastersky J, Nicaise C, Longeval E, Stryckmans P, and the EORTC Lung Cancer Working Party: Cisplatin, Adriamycin and etoposide (CAV) for remission induction of small-cell bronchogenic carcinoma. Evaluation of efficacy and toxicity and pilot study of a «late intensification» with autologous bone-marrow rescue. Cancer 50:652–658, 1982.PubMedCrossRefGoogle Scholar
  43. 43.
    Stewart P, Buckner CD, Thomas ED, Bagley C, Bensinger W, Clift RA, Appelbaum FR, Sanders J: Intensive chemoradiotherapy with autologous marrow transplantation for small-cell carcinoma of the lung. Cancer Treat Rep 67:1055–1059, 1983.PubMedGoogle Scholar
  44. 44.
    Smith IE, Evans BD, Harland SJ, Robinson BA, Yarnold JR, Glees JG, Ford HT: High-dose cyclophosphamide with autologous bone-marrow rescue after conventional chemotherapy in the treatment of small-cell lung carcinoma. Cancer Chemother Pharmacol 14:120–124, 1985.PubMedCrossRefGoogle Scholar
  45. 45.
    Banham S, Dorward A, Hutcheon A, Ahmedzaï S, Cunningham D, Burnett A, Soukop M, Lucie N, Kaye S: The role of VP16 in the treatment of small-cell lung cancer: studies of the West of Scotland Lung Cancer Group. Semin Oncol 12 (Suppl 2):2–6, 1985.PubMedGoogle Scholar
  46. 46.
    Sculier JP, Klastersky J, Stryckmans P, and the EORTC Lung Cancer Working Party (Belgium): Late intensification in small-cell lung cancer: a phase I study of high doses of cyclophosphamide and etoposide with autologous bone marrow transplantation. J Clin Oncol 3:184–191, 1985.PubMedGoogle Scholar
  47. 47.
    Spitzer G, Farha P, Valdivieso M, Dicke H, Zander A, Vellekoop L, Murphy NK, Dhingra HM, Umsawasdi T, Chiuten D, Carrs DT: High-dose intensification therapy with autologous bone marrow support for limited small-cell bronchogenic carcinoma. J Clin Onol 4:4–13, 1986.Google Scholar
  48. 48.
    Ihde DC, Deisseroth AB, Lichter AS, Bunn PA, Carney DN, Cohen MH, Veach SR, Makuch RW, Johnston-Early A, Abrams RA, Messer-Schmidt GL, Matthews MJ, Minna JD: Late intensive combined modality therapy followed by autologous bone marrow infusion in extensive-stage small-cell lung cancer. J Clin Oncol 4:1443–1454, 1986.PubMedGoogle Scholar
  49. 49.
    Humblet Y, Symann M, Bosly A, De Launois L, Francis C, Machiels J, Beauduin M, Doyen C, Weynants P, Longueville J, Prignot J: Late intensification chemotherapy with autologous bone marrow transplantationin selected small-cell carcinoma of the lung. J Clin Oncol, in press.Google Scholar
  50. 50.
    Sculier JP, Klastersky J, Stryckmans P, and EORTC Lung Cancer Working Party (Belgium): Chimiothérapie intensive tardive avec autogreffe de moelle. Etude pilot dans les cancers bronchiques anaplasiques a petites cellules. Presse Médicale 12:677–680, 1983.Google Scholar
  51. 51.
    Sculier JP, Klastersky J, Stryckmans P: Late intensive chemotherapy with autologous bone marrow transplantation in small cell lung cancer: preliminary report of a pilot study. In: Mc Vie JG, Dalesio D, Smith IE (eds): Autologous Bone Marrow Transplantation and Solid Tumours. New York, Raven Press, 1984, pp 111–123.Google Scholar

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© Kluwer Academic Publishers, Boston 1989

Authors and Affiliations

  • J. P. Sculier
  • J. Klastersky

There are no affiliations available

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