32 . Lung cancer, small cell (SCLC)
32.1 General considerations
|
Stage grouping |
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Stage0 Tis N0 M0 |
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StageIA T1 N0 M0 |
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StageIB T2 N0 M0 |
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StageIIA T1 N1 M0 |
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StageIIB T2 N1 M0 T3 N0 M0 |
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StageIIIA T1 N2 M0 T2 N2 M0 T3 N1,2 M0 |
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StageIIIB T4 any N M0 any T N3 M0 |
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Stage IV any T any N M1 |
Limited disease(stage 0-IIIB) confined to one hemithorax
- With or without ipsilateral or contralateral mediastinal or supraclavicular lymph node metastasis.
- with or without ipsilateral pleural effusions independent of cytology
Extensive (stage IV): Any disease at sites beyond the definition of limited disease
At the time of diagnosis SCLC typically is a systemic disease, requiring
systemic treatment. Only for a few patients with very limited
disease(T1,N0,M0) surgical resection (with or without subsequent
radiation and /or chemotherapy)is the treatment of choice.
Patients who present with bulky limited-stage disease are treated with combination chemotherapy (often in conjunction with thoracic and prophylactic cranial radiation ).Chemotherapy is also the cornerstone of treatment for patients with extensive-stage disease and a good performance status, whereas best supportive care may be an
option for those with a poor performance status.
Patients who either relapse after successful first-line therapy (sensitive patients) or progress within or short time after first-line therapy(refractory patients) are candidates for salvage chemotherapy if performance status is adequate:either re-induction
chemotherapy (for sensitive patients) or new agents/new combinations(for refractory and sensitive patients).
Literature: for review e.g.
ARDIZZONI and GROSSI,Ann.Oncol.11(Suppl 3)(2000):101-108
CHUTE et al, J.Clin.Oncol.17(1999): 1794-1801(overview of
Cooperative group studies performed in North America over the
past 20 years with extensive Stage SCLC).
CURRAN,Semin.Oncol. 28 (Suppl 4)(2001):14-22 and Cancer
Treat. Res.105(2001):229-252 (combined-modality therapy for
limited-stage SCLC)
HUISMAN et al,Cancer Treat.Rev.25(1999):199-206(second-line
chemotherapy)
KELLY,Cancer Treat.Res.105(2001):253-276(treatment of
extensive stage SCLC).
MASCAUX et al, Lung Cancer 30(2000):23-36(systematic review
and meta-analysis of the role of etoposide and cisplatin)
MEERT et al, BMJ Cancer 1(2001):5 (meta-analysis of
prophylactic cranial irradiation).
176 Lung Cancer, small cell (SCLC)
POSTMUS and SMIT,Semin.Oncol.28(Suppl 4)(2001):48-52(treatment of
relapsed SCLC)
PUJOL et al, Br.J.Cancer 83(2000):8-15(meta-analysis of the role of
cisplatin-containing regimens).
SCHILLER,Oncology 61 (Supple 1)(2001):3-13(standards of care in
SCLC and NSCLC)
SCHUETTE, Lung Cancer 33(Suppl 1)(2001):99-107
TURRISI and SHERMAN, Eur.J.Cancer 38(2002):279-291(limited stage
SCLC) WOLF,Lung Cancer 33(Suppl 1)(2001):125-135
32.2 CAV(ACO)
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Doxorubicin 50mg/m² i.v.(short inf) d1 |
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Cyclophosphamide 1000mg/m² i.v.(short inf) d1 |
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Vincristine 2mg i.v.(bolus) d1 |
To be repeated every 3 weeks
Literature:
GRECO et al.Am.J.Med.66(1979):625-630
32.3 CEV (EPICO)
|
Epirubicin 70mg/m² i.v.(short inf) d1 |
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Cyclophosphamide 1000mg/m² i.v.(short inf) d1 |
|
Vincristine 2mg i.v.(short inf) d1 |
To be repeated every 3 weeks
Literature:
VERONESI et al,Eur.J.Cancer 30A(1994):1474-1478
32.4 PE (EP)
Literature: for review
AISNER and ABRAMS,Semin.Oncol.16(Suppl 6)(1989):2-9
Numerous variations, e.g.
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Cisplatin 80mg/m i.v.(1 h inf) d1 |
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Etoposide 100mg/m i.v.(2 h inf) d1-3 |
To be repeated every 3 weeks
Literature:
EVANS et al, Ann. Intern. Med.107(1987):451-458
ROTH et al, J.Clin.Oncol.10(1992):282-291
or
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Cisplatin 60mg/m² i.v.(1 h inf) d1 |
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Etoposide 120mg/m² i.v.(2 h inf) d1-3 |
To be repeated every 3 weeks(4 cycles)with concurrent thoracic radiotherapy(total dose of 45 Gy, given either once or twice daily beginning with cycle 1 of the chemotherapy . Patients on once-daily therapy received 1.8 Gy/d in 25 fractions over 5 weeks. Accelerated twice-daily therapy involved the administration of 1.5 Gy in 30 fractions over 3 weeks).
Lung Cancer, small cell (SCLC) 177
Litrature:
TURRISI et al, N.Engl.J.Med. 340 (1999):265-271
32.5 CE (EC)
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Carboplatin 300mg/m² i.v.(short inf) d1 |
|
Etoposide 120mg/m² i.v(2 h inf) d1-3 |
To be repeated every 4 weeks
Literature:
BISHOP et al. J.Clin.Oncol. 5 (1987):1574-1578
SKARLOS et al, Ann.Oncol.5 (1994):601-607
32.6 CAV/PE (alternating or sequential)
Especially for patients with limited disease in combination with thoracic radiotherapy.
Literature:
JOHNSON et al, J.Clin.Oncol.14 (1996):806-813
MURRAY et al, J.Clin. Oncol.17(1999):2300-2308
UEOKA et al, Cancer 83(1998):283-290
WORK et al, J.Clin.Oncol.15(1997):3030-3037
32.7 CAE (CDE , ACE)
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Cyclophosphamide 1000mg/m² i.v.(bolus) d1 |
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Doxorubicin 40-50mg/m² i.v.(bolus) d1 |
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Etoposide 100-120mg/m² i.v.(1 h inf) d1-3 or 150mg/m² i.v.(1 h inf) d1+2 |
To be repeated every 3 weeks (5 courses followed by thoracic
radiotherapy in patients with limited disease*).
Literature:
AISNER et al, Semin.Oncol.13 (Suppl 3)(1986):54-62
BUNN et al, Semin. Oncol.13(1986):45-53
*GREGOR et al, J.Clin.Oncol.15(1997):2840-2849
KLASTERSKY et al,Cancer 56(1985):71-75
URBAN et al, Cancer 86(1999):2238-2245(randomized trial of CDE vs
cisplatin added to CDE)
or
Dose-intensified ACE
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Cyclophosphamide 1000mg/m² i.v.(bolus) d1 |
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Doxorubicin 40mg/m² i.v.(bolus) d1 |
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Etoposide 120mg/m² i.v.(30 min inf) d2+3 and 240mg/m² p.o. d4-14 |
To be repeated every 2 weeks(with G-CSF support)
Literature:
THATCHER et al,J.Clin.Oncol.18(2000):395-404 (randomized trial of the British Medical Research Council of six cycles of ACE either every three weeks or every two weeks with G-CSF).
178 Lung Cancer,small cell(SCLC)
32.8 (V-) ICE
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Carboplatin 300mg/m² i.v.(1 h inf) d1 |
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Ifostamide 5000mg/m² i.v.(24 h inf) d1 with mesna uroprotection |
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Etoposide 120mg/m² i.v.(30 min inf) d1+2 and 240mg/m² p.o. d3 |
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Vincristine 1.0mg i.v.(bolus) d15 |
To be repeated every 4 weeks
Literature :
PRENDIVILLE et al, Eur.J.Cancer 30 A(1994):2085-2090
By using granulocyte or granulocyte-macrophage colony-stimulating factor/hematopoietic progenitor cells, the therapy-free interval can be reduced to three or two weeks(without midcycle vincristine!).
Literature:
PETTENGELL et al, J.Clin.Oncol.13(1995):148-156
STEWARD et al, J.Clin. Oncol.16(1998):642-650
WOLL et al, J. Clin.Oncol. 13 (1995):652-659
32.9 VIP
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Etoposide 75mg/m² i.v. d1-4 |
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Ifosfamide 1200mg/m² i.v. d1-4 with mesna uroprotection |
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Cisplatin 20mg/m² i.v. d1-4 |
To be repeated every 3 weeks
Literature:
LOEHRER et al, J.Clin.Oncol.13(1995): 2594-2599
32.10 “Newer” drugs
Several “newer” drugs (taxanes, camptothecins ,gemcitabine)
showed promising activity in the first-line and second-line
therapy of small cell lung cancer which justifies their
incorporation into combination chemotherapy regimens.
Literature: for review e.g.
ARGIRIS and MURREN,Cancer J.7 (2001):228-235
KELLY,Chest 117 (Suppl 1)(2000):156-162
32.10.1 Paclitaxel
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Paclitaxel 250mg/m² i.v.(24 h inf) d1,8,15….. |
Literature:
ETTINGER et al, J.Clin. Oncol.13 (1995):1430-1435
32.10.2 Topotecan
Literature: for review
HUANG and TREAT,Oncology 61(Suppl 1)(2001):14-24
SCHILLER,Oncology 61(Suppl 1)(2001):55-59
|
Topotecan 1.5mg/m² i.v.(30 min inf) d1-5 |
To be repeated every 3 weeks
Literature:
Von PAWEL et al,J.Clin.Oncol.17(1999):658-667
SCHILLER et al, J.Clin.Oncol.19(2001):2114-2122
32.11 Paclitaxel + Carboplatin
(For salvage chemotherapy in patients resistant to CDE)
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Paclitaxel 175mg/m² i.v.(3 h inf) d1 |
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Carboplatin AUC=7* i.v.(30 min inf) d1 |
To be repeated every 3 weeks (5 cycles)
* Chatelut formula
Literature:
GROEN et al, J.Clin. Oncol. 17(1999):927-932
32.12 Oral etoposide
Based on the available data, the use of single agent oral
etoposide for palliation is discussed controversially.
Literature:
CLARK,Drug 58 (Suppl 3)(1999): 17-20 (review article on the
current role of oral etoposide in the management of SCLC)
SOUHAMI et al,J.Natl.Cancer Inst .89 (1997):577-580
(randomized study in which oral etoposide was inferior to
intravenous standard combination chemotherapy)
32.13 Brain metastases
See also 17.7
Literature: for review
GROSSI et al, Crit.Rev.Oncol.Hematol.37(2001):61-67
POSTMUS and SMIT,Ann.Oncol.10(1999):753-759