Improvements in small cell lung cancer (SCLC) therapy with conventional doses of drugs with or without radiotherapy have been poor, and the 5-year survival is discouraging. Since SCLC is highly sensitive to radiotherapy and chemotherapy, some studies have tried to improve survival by increasing the dose of the drugs. Within conventional ranges, dose intensity can be increased with the support of hematopoietic growth factors (G/GM-CSF) and/or shortening treatment intervals (eg weekly regimens). However, dose intensity could be increased by only 20-30% and a survival advantage was not definitively obtained. Given its high chemosensitivity already two decades ago, SCLC was one of the first malignancies deemed suitable for maximizing dose and dose intensity with the support of autologous bone marrow transplantation (ABMT). On the whole, results were disappointing and the procedure was nearly abandoned. Nowadays, some interest is emerging again due to the improvements in supportive care such as the availability of hematopoietic growth factors and the peripheral blood progenitor cells (PBPC).
SouhamiR.L., HarperP.G., LinchD., TraskC., GoldstoneA.H., TobiasJ., SpiroS.G., GeddesD.M., RichardsD.M.: High-dose cyclophosphamide with autologous marrow transplantation as initial treatment of small cell carcinoma of the bronchus. Cancer Chemother Pharmacol, 8: 31–34, 1982.
2.
SouhamiR.L., HarperP.G., LinchD., TraskC., GoldstoneA.H., TobiasJ.S., SpiroS.G., GeddesD.M., RichardsD.M.: High-dose cyclophosphamide with autologous marrow transplantation for small cell carcinoma of the bronchus. Cancer Chemother Pharmacol, 10: 205–207, 1983.
3.
SouhamiR.L., FinnG., GregoryW.M., BirkheadB.G., BuckmanR., EdwardsD., GoldstoneA.H., HarperP.G., SpiroS.G., TobiasJ.S., GeddesD.: High-dose cyclophosphamide in small-cell carcinoma of the lung. J Clin Oncol, 3: 958–963, 1985.
4.
SouhamiR.L., HajichristouH.T., MilesD.W., EarlH.M., HarperP.G., AshC.M., GoldstoneA.H., SpiroS.G., GeddesD.M., TobiasJ.S.: Intensive chemotherapy with autologous bone marrow transplantation for small-cell lung cancer. Cancer Chemother Pharmacol, 24: 321–325, 1989.
5.
GregoryW.M., BirkheadB.G., SouhamiR.L.: A mathematical model of drug resistance applied to treatment for smallcell lung cancer. J Clin Oncol, 6: 457–461, 1988.
6.
FarhaP., SpitzerG., ValdiviesoM., DickeK.A., ZanderA., DhingraH.M., MinnhaarG., VellekoopL., VermaD.S., UmsawasdiT., ChiutenD.: High-dose chemotherapy and autologous bone marrow transplantation for the treatment of small cell lung carcinoma. Cancer, 52: 1351–1355, 1983.
7.
LittlewoodT.J., BentleyD.P., SmithA.P.: 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.
8.
LeyvrazS., KettererN., PereyL., BauerJ., VuichardP., GrodJ. Ph., SchneiderPh, von FliednerV., LejeuneF., BachmannF.: Intensification of chemotherapy for the treatment of solid tumours: feasibility of a 3-fold increase in dose intensity with peripheral blood progenitor cells and granulocyte colony-stimulating factor. Br J Cancer, 72: 178–182, 1995.
9.
Van de VeldeH., BosquéeL., WeynantsP., CanonJ.L., RosierJ.F., HumbletY.: Moderate dose-escalation of combination chemotherapy with concomitant thoracic radiotherapy in limited disease small cell lung cancer: prolonged intrathoracic tumour control and high central nervous system relapse rate. Ann Oncol, 10: 1051–1057, 1999.
10.
LeyvrazS., PereyL., RostiG., LangeA., PampallonaS., PetersR., HumbletY., BosquéeL., PasiniF., MarangoloM.: Multiple courses of high-dose ifosfamide, carboplatin, and etoposide with peripheral-blood progenitor cells and filgrastim for small cell lung cancer: a feasibility study by the European Group for Blood and Marrow Transplantation. J Clin Oncol, 17: 3531–3539, 1999.
11.
KlasterskyJ., NicaiseC., LongevalE., StryckmansP. and the EORTC Lung Cancer Working Party: Cisplatin, adriamycin, and etoposide (CAV) for remission induction of small cell bronchogenic carcinoma. Cancer, 50: 652–658, 1982.
12.
StewartP., BucknerC.D., ThomasE.D., BagleyC., BensingerW., CliftR.A., AppelbaumF.R., SandersJ.: Intensive chemoradiotherapy with autologous marrow transplantation for small cell carcinoma of the lung. Cancer Treat Rep, 67: 1055–1059, 1983.
13.
StahelR.A., TakvorianR.W., SkarinA.T., CanellosG.P.: Autologous bone marrow transplantation following high-dose chemotherapy with cyclophosphamide, BCNU and VP-16 in small cell carcinoma of the lung and a review of current literature. Eur J Cancer Clin Oncol, 20: 1233–1238, 1984.
14.
SmithI.E., EvansB.D., HarlandS.J.: High-dose cyclophosphamide (7 g/m2) with or without autologous bone marrow rescue after conventional chemotherapy in the treatment of patients with small cell lung cancer. Cancer Treatment Reviews, 10(suppl A), 79–81, 1983.
15.
SmithI.E., EvansB.D., HarlandS.J., RobinsonB.A., YarnoldJ.R., GleesJ.G., FordH.T.: 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.
16.
CunninghamD., BanhamS.W., HutcheonA.H., DorwardA., AhmedzaiS., TanseyP., SoukopM., StevensonR.D., StackB.R., KayeS.B., LucieN., BurnettA.K.: High-dose cyclophosphamide and VP 16 as late dosage intensification therapy for small cell carcinoma of lung. Cancer Chemother Pharmacol, 15: 303–306, 1985.
17.
SculierJ.P., KlasterskyJ., StryckmansP. 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.
18.
IhdeD.C., DeisserothA.B., LichterA.S., BunnP.A., CarneyD.N., CohenM.H., VeachS.R., MakuchR.W., Johnston-EarlyA., AbramsR.A., MesserschmidtG.L., MatthewsM.J., MinnaJ.D.: 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.
19.
SpitzerG., FarhaP., ValdiviesoM., DickeK., ZanderA., VellekoopL., MurphyW.K., DhingraH.M., UmsawasdiT., ChiutenD., CarrD.T.: High-dose intensification therapy with autologous bone marrow support for limited small-cell bronchogenic carcinoma. J Clin Oncol, 4: 4–13, 1986.
20.
SpitzerG., SpencerV., DunphyF.: High-dose chemotherapy with autologous bone marrow support for lung cancer. In: High-Dose Cancer Chemotherapy, Pharmacology, Hemopoietins, Stem Cells, ArmitageJ.O., AntmanK.H. (Eds.), pp. 719–728, Williams & Wilkins, Baltimore, 1992.
21.
PicoJ.L., BaumeD., OstronoffM., BeaujeanF., GouyetteA., Le ChevalierT., ArriagadaR., RebattuP., HayatM.: Chimiotherapie a hautes doses suivie d'autogreffe de moelle osseuse dans le traitement du cancer bronchique a petites cellules. Bull Cancer, 74: 587–595, 1987.
22.
HumbletY., SymannM., BoslyA., DelaunoisL., FrancisC., MachielsJ., BeauduinM., DoyenC., WeynantsP., LonguevilleJ., PrignotJ.: Late intensification chemotherapy with autologous bone marrow transplantation in selected small-cell carcinoma of the lung: a randomized study. J Clin Oncol, 5: 1864–1873, 1987.
23.
WilsonC., PickeringD., StewartS., VallisK., KalofonosH., CrosA., SnookD., GoldmanJ.M., McKenzieC.G., EpenetosA.A.: High-dose cyclophosphamide with autologous bone marrow rescue in small cell lung cancer. In Vivo, 2: 331–334, 1988.
24.
MarangoloM., RostiG., AmadoriD., LeoniM., ArdizzoneA., FiorentiniG., CrucianiG., TienghiA., RavaioliA., SebastianiL., TurciD., CotignoliT., ArgnaniM., FlaminiE., RossoR.: High-dose etoposide and autologous bone marrow transplantation as intensification treatment in small cell lung cancer: a pilot study. Bone Marrow Transpl, 4: 405–408, 1989.
25.
LangeA., KolodziejJ., TomeczkoJ., ToporskiJ., SedezimirskaM., JazwiecB., BochenskaJ., MrozE., BieleckaE., WasA., GlejzerO., Tomaszewska-ToporowskaB., JagasM., ZukowskaB., SpaltensteinA., BieranowskaD., KlimczakA.: Aggressive chemotherapy with autologous bone marrow transplantation in small cell lung carcinoma. Arch Immunol Ther Exp (-Warsz), 39: 431–439, 1991.
JennisA., LevitanN., PecoraA.L., IsaacsR., LazarusH.: Sequential high dose chemotherapy (HDC) with filgrastim/peripheral stem cell support (PSCS) in extensive stage small cell lung cancer (SCLS) (abstract). Proc Am Soc Clin Oncol, 15: 1021, 1996.
30.
FetscherS., BruggerW., EngelhardtR., KanzL., HasseJ., FrommholdH., WengerM., LangeW., MertelsmannR.: Dose intense therapy with etoposide, ifostamide, cisplatin, and epirubicin (VIP-E) in 100 consecutive patients with limited- and extensive-disease small-cell lung cancer. Ann Oncol, 8: 49–56, 1997.
31.
BesshoA., UeokaH., KiuraK., TabataM., SunamiK., KatayamaY., YamaneH., HirakiA., HaradaM.: High-dose ifosfamide, carboplatin and etoposide with autologous peripheral blood progenitor cell transplantation for small-cell lung cancer. Anticancer Res, 19: 693–698, 1999.
32.
LazarusH.M., EliasA.D.: Autologous bone marrow and peripheral blood progenitor cell tranplants in small cell lung cancer. Bone Marrow Transpl, 17: 1–3, 1996.
33.
PignonJ.P., ArriagadaR., IdheD.C., JohnsonD.H., PerryM.C., SouhamiR.L., BrodinO., JossR.A., KiesM.S., LebeauB., OnoshiT., ØsterlindK., TattersallM.H., Wagner: A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med, 327: 1616–1624, 1992.
34.
CoiffierB., PhilipT., BurnettA.K., SymannM.L.: Consensus conference on intensive chemotherapy plus hematopoietic stem-cell transplantation in malignancies: Lyon, France, June 4-6, 1993. J Clin Oncol, 12: 226–231, 1994.
35.
ChoiN.C., HerndonJ.E.2nd, RosenmanJ., CareyR.W., ChungC.T., BernardS., LeoneL., SeagrenS., GreenM.: Phase I study to determine the maximum-tolerated dose of radiation in standard daily and hyperfractionated-accelerated twice-daily radiation schedules with concurrent chemotherapy for limited-stage small-cell lung cancer. J Clin Oncol, 16: 3528–3536, 1998.
36.
TurrisiA.T.3rd, KimK., BlumR., SauseW.T., LivingstonR.B., KomakiR., WagnerH., AisnerS., JohnsonD.H.: Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med, 28: 265–271, 1999.
37.
ArriagadaR., Le ChevalierT., BorieF., RivièreA., ChomyP., MonnetI., TardivonA., ViaderF., TarayreM., BenhamouS.: Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. J Natl Cancer Inst, 87: 183–190, 1995.
38.
GregorA., CullA., StephensR.J., KirkpatrickJ.A., YarnoldJ.R., GirlingD.J., MacbethF.R., StourtR., MachinD.: Prophylactic cranial irradiation is indicated following complete response to induction therapy in small cell lung cancer: results of a multicentre randomised trial. Eur J Cancer, 11: 1752–1758, 1997.
39.
AuperinA., ArriagadaR., PignonJ.P., Le PechouxC., GregorA., StephensR.J., KristjansenP.E., JohnsonB.E., UeokaH., WagnerH., AisnerJ.: Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med, 12: 476–484, 1999.
40.
PasiniF., CettoG.L., PelosiG.: Does bone marrow involvement affect prognosis in small-cell lung cancer?Ann Oncol, 9: 247–250, 1998.
41.
BruggerW., BrossK., GlattM., WeberF., MertelsmannR., KanzL.: Mobilisation of tumour cells and hematopoietic progenitor cells into peripheral blood of patients with solid tumors. Blood, 83: 636–640, 1994.
42.
PelosiG., PasiniF., OttensmeierC., PavanelF., BresaolaE., BonettiA., FraggettaF., TerziA., IannucciA., CettoG.L.: Immunocytochemical assessment of bone marrow aspirates for monitoring response to chemotherapy in small-cell lung cancer patients. Br J Cancer, 81: 1213–1221, 1999.
43.
GoldmanJ.M., SchmitzN., NiethammerD., GratwohlA.: Allogeneic and autologous transplantation for hematologic diseases, solid tumors and immune diseases: current practice in Europe in 1998. Bone Marrow Transplant, 21: 1–7, 1998.
44.
MacNeilM., EisenhauerE.A.: High-dose chemotherapy: is it standard management for any common solid tumour?Ann Oncol, 10: 1145–1161, 1999.
