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Update on small cell lung cancer management

Rudolf M. Huber, Amanda Tufman
Breathe 2012 8: 314-330; DOI: 10.1183/20734735.013211
Rudolf M. Huber
Division of Respiratory Medicine and Thoracic Oncology, University of Munich – Campus Innenstadt, Munich, Germany
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  • For correspondence: huber@med.uni-muenchen.de
Amanda Tufman
Division of Respiratory Medicine and Thoracic Oncology, University of Munich – Campus Innenstadt, Munich, Germany
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Tables

  • Table 1 Paraneoplastic syndromes associated with lung cancer [5, 6]
    SyndromePatients affected %Causative protein or antibody
    Hyponatraemia/SIADH15Arginine vasopressin or atrial natriuretic peptide
    Ectopic corticotropin syndrome2–5Corticotropin
    Lambert–Eaton myasthenic syndrome3Voltage-gated calcium channel antibody
    Acromegaly<1GHRH
    Gynaecomastia<1
    Hypercoagulability<1
    Thrombocytosis<1
    Encephalomyelitis/subacute sensory neuropathy<1Anti-Hu, amphiphysin, CV2
    Cancer-associated retinopathy<1Anti-recoverin
    Dermatomyositis<1
    Acanthosis palmaris, erythema gyratum repens<1
    Nephrotic syndrome<1
    • SIADH: syndrome of inadequate antidiuretic hormone; GHRH: growth hormone-releasing hormone.

  • Table 2 Small cell lung cancer: survival according to extent of disease at presentation [11] modified by therapy [12]
    LD: tumour limited to one potential irradiation fieldED: not confined to one hemithorax, malignant pleural effusion or distant metastases
    Median survival of all patients16–24 months6–12 months
    5-year survival of all patients14%Rare
    Supportive care3 months1.5 months
    Single-agent chemotherapy6 months4 months
    Combined chemotherapy10–14 months7–11 months
     5-year survival2–8%0–1%
    Chemotherapy plus radiation12–16 months7–11 months
     5-year survival6–12%0–1%
    • LD: limited disease; ED: extensive disease.

  • Table 3 TNM staging of lung cancer [15]
    Occult carcinomaTxN0M0
    Stage 0Tis
    Stage IAT1a–T1bN0M0
    Stage IBT2aN0M0
    Stage IIAT1a–T2aN1M0
    T2bN0M0
    Stage IIBT2bN1M0
    T3N0M0
    Stage IIIAT1a–T3N2M0
    T3N1M0
    T4N0–N1M0
    Stage IIIBT4N2M0
    T1a–T4N3M0
    Stage IVAny TAny NM1a or M1b
  • Table 4 WHO/IASLC Subtypes of neuroendocrine tumours [20]
    SubtypeCharacteristics
    Classical SCLCSmall round, oval or spindle-shaped cells with scant cytoplasm, ill-defined borders, finely granular nuclear chromatin and absent or inconspicuous nucleoli. High mitotic count. Characteristic crush phenomena due to the soft texture of the tumour and mechanical alterations. Histomorphological grading G1 to G4 not applicable.
    Typical/atypical carcinoidUsually less aggressive tumour.
    Large cell neuroendocrine tumourProliferation index relevant for classification.
    Combined SCLCSmall-cell carcinoma with an additional component of any of the histological types of NSCLC
    • WHO: World Health Organization; IASLC: International Association for the Study of Lung Cancer; SCLC: small cell lung cancer; NSCLC: non-small cell lung cancer.

  • Table 5 Some genetic alterations in small cell lung cancer (SCLC) [23, 24]
    Gene (locus)AlterationPossible drug/therapeutic targeting abnormalities
    FHIT (3p14.2)Loss (80% of SCLC)
    RASSF1 (3p21.3)Loss (>90% of SCLC)
    RARB (3p24)Loss (72% of SCLC)
    TP53 (17p13.1)Mutation and deletion (>75% of SCLC)p53 adenoviral vector (Advexin)
    c-KitOverexpressedTyrosine kinase inhibitor (imatinib)
    SrcConstitutively activatedSrc inhibitor (dasatinib)
    c-MetAmplified, overexpressed or mutatedsiRNA, c-Met inhibitor SU11274
    RB1Altered (>90% of SCLC)
    PI3K/Akt/mTORConstitutively activatedPI3K inhibitor (LY294002) mTOR inhibitor (rapamycin) and its derivatives (CCI-779, RAD001, AP23576)
    Bcl-2OverexpressedAntisense oligonucleotide (oblimersen sodium) Inhibitor of Bcl-2 (ABT-737)
    VEGFOverexpressedHumanised monoclonal antibody (bevacizumab) VEGFR-2 and EGFR inhibitor (ZD6474)
    • FHIT: fragile histidine triad; RASSF: Ras-association domain family; RARB: retinoic acid receptor-β; TP53: tumour protein p53; RB: retinoblastoma; PI3K: phosphoinositide 3-kinase; mTOR: mammalian target of rapamycin; Bcl: B-cell lymphoma; VEGF: vascular endothelial growth factor; siRNA: small interfering RNA; EGFR: epidermal growth factor.

  • Table 6 Widely used chemotherapeutic regimens with effect against small cell lung cancer [6]
    RegimenDosageApplicationCycles/Precautions
    CisEtoEvery 3 weeks, or after nadir, normal renal function and diuretics are mandatory
     Cisplatin80 mg·m−2i.v. d1
     Etoposide100 mg·m−2i.v. d1–d3
    ACO-I after Livingston and SeeberEvery 3 weeks; vincristine dosage has to be adjusted to age; >60 years reduce to 1 mg·m−2
     Adriamycin60 mg·m−2i.v. d1
     Cyclophosphamide750 mg·m−2i.v. d1
     Vincristine2 mg·m−2i.v. d1/d8/d16
    ACE combination after Klastersky
     Adriamycin45 mg·m−2i.v. d1
     Cyclophosphamide1000 mg·m−2i.v. d1
     Etoposide80 mg·m−2i.v. d1–d3Every 3 weeks.
    EpiCO therapy after DringsEvery 3 weeks; vincristine dosage has to be adjusted to age; >60 years reduce to 1 mg·m−2
     Epirubicin70 mg·m−2i.v. d1
     Cyclophosphamide1000 mg·m−2i.v. d1
     Vincristine2 mg·m−2i.v. d1/d8/d16
    Carboplatin/etoposideEvery 3 weeks, or after nadir, normal renal function and diuretics are mandatory
     CarboplatinAUC 5i.v. d1
     Etoposide100 mg·m−2i.v. d1-d3
    Paclitaxel/etoposide/carboplatinEvery 3 weeks, steroids to prevent anaphylactic crisis after administration of paclitaxel is mandatory
     Paclitaxel175 mg·m−2i.v. for 3 h
     CarboplatinAUC 5d4
     EtoposideI–III: 100 mg·m−2i.v. d4
    IV: 100 mg·m−2d1–d3
    Cisplatin/irinotecanAtropine 0.25 mg 1/2 h before irinotecan s.c. Every 4 weeks and/or after nadir; diarrhoea is common
     Cisplatin60 mg·m−2i.v. d1
     Irinotecan60 mg·m−2i.v. d 1, 8,15
    Topotecan (second-line)
     Topotecan1.25 mg·m−2 with subsequent dose adjustment according to haematological toxicityi.v. d 1–5Every 3 weeks and/or after reaching normal laboratory values
  • Table 7 Small cell lung cancer: response to newer agents [6, 34–38]
    AgentResponse rate (%)
    Paclitaxel34–41
    Irinotecan47#
    Topotecan39
    Docetaxel28#
    Gemcitabine26
    Vinorelbine12.5#
    Bendamustine72.7% first-line in combination with carboplatin
    Amrubicin21.3# (refractory patients), 44# (sensitive patients)
    • #: previously treated patients only.

  • Table 8 Treatment of brain metastases by radiotherapy modified from [32]
    First author [ref.]Patients nCR+PR %CR %Median survival months (range)
    Nugent [39]68923
    Cox [40]4075384 (0–21)
    Baglan [41]4785644
    Hirsch [42]4546
    Lucas [43]395625(1–28)
    Carmichael [44]6163327 (1–18)
    Gianonne [37]41857011 (1–24)
    • CR: complete response; PR: partial respose.

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Update on small cell lung cancer management
Rudolf M. Huber, Amanda Tufman
Breathe Jun 2012, 8 (4) 314-330; DOI: 10.1183/20734735.013211

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Update on small cell lung cancer management
Rudolf M. Huber, Amanda Tufman
Breathe Jun 2012, 8 (4) 314-330; DOI: 10.1183/20734735.013211
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