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Pneumologie 1999; 53(10): 485-487
DOI: 10.1055/s-1999-9042
ORIGINALARBEIT
Georg Thieme Verlag Stuttgart ·New York

Kombinierte alternierende Chemo-Strahlentherapie beim kleinzelligen Bronchialkarzinom im Stadium III (TNM) (limited disease): Eine Phase-II-Studie mit Carboplatin/Etoposid/Vincristin und alternierender Strahlentherapie[1]

Combined Alternating Radiochemotherapy in Stage III Small-Cell Carcinoma of the Lung (Limited Disease). A Phase II Study with Carboplatin/Etoposide/Vincristine and Alternating Radiotherapy:M. Serke1 , U. Riedel1 , N. Schönfeld1 , J. Pannhorst2 , B. Förster2 , R. Loddenkemper1
  • 1Lungenklinik Heckeshorn, Pneumologie II, Berlin (Leiter: Prof. Dr. R. Loddenkemper)
  • 2Strahlenklinik des Universitätsklinikums der Humboldt- Universität Berlin Charité, Campus Virchow-Klinikum (Leiter: Prof. Dr. Felix)
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Publication History

Publication Date:
31 December 1999 (online)

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Zusammenfassung:

Hintergrund: Die kombinierte alternierende Chemo-Strahlentherapie des SCLC im Stadium III wird im Rahmen einer prospektiven Studie untersucht und im Rahmen der vorhandenen Literatur diskutiert. Methode: Geprüft wird ein alternierendes Regime von Chemotherapie (Carboplatin: AUC5, Etoposid: 3 × 120 mg/m2, Vincristin: 2 mg d1, WH d 28) und Strahlentherapie (1 × 4 Gy/Woche) an 32 Patienten im Stadium IIIa und IIIb. Ergebnisse: Die kombinierte Strahlentherapie wird mit geringer Toxizität toleriert, wobei dosislimitierend die Hämatotoxizität war. Die Ergebnisse sind gut mit einem Response von 75 %, einem medianen Überleben von 14,5 Monaten und einem 2-Jahres-Überleben von 34 %. Zur Zeit werden 5 Langzeitüberlebende (über 29 Monate) beobachtet. Sowohl Lokal- als auch Fernrezidive treten in gleicher Häufigkeit (je 34 %) auf. Schlußfolgerungen: Die kombinierte Strahlen-Chemotherapie beim SCLC im Stadium III ist mit dem hier geprüften Regime gut praktikabel. Sie verspricht eine hohe Ansprechrate und ein günstiges 2-Jahres-Überleben. Lokal- und Fernrezidive treten in gleicher Häufigkeit auf und unterstreichen die Notwendigkeit sowohl einer besseren lokalen als auch systemischen Kontrolle.

Background: The combination of radio-chemotherapy is accepted standard in limited-disease small cell lung cancer, but the best way of combining the two modalities is still unknown. To test an alternating regime of early radiotherapy with hypofractionated radiotherapy we performed a phase II study in stage III small cell lung cancer. Method: 32 SCLC patients (n = 7 IIIa, n = 25 IIIb) were treated with a weekly alternating regime with either chemotherapy or radiotherapy. Chemotherapy included carboplatin (AUC5), etoposide (3 × 120 mg/m2) and vincristine (2 mg), repeated on day 28 for six cycles. Radiotherapy started one week before chemotherapy and was applied weekly 1 × 4 Gy, using a split-course regimen. Results: Combined radio-chemotherapy was well tolerated with dose-limiting hemotoxicity and very few cases of oesophagitis. Overall response was 75 %, median survival 14.5 months and the 2-year survival was 34.4 %. 5 patients are still living now for more than 29 months. Treatment failure was local and systemic in 34 % of the patients. Systemic failure included 6 patients with brain metastases. Conclusion: Combined radio-therapy in small-cell lung cancer using an alternating hypofractionated regimen is well tolerated. Response rate and 2-year survival are promising. Local and systemic failure is an ongoing problem and requires better local and systemic control of the disease.

1 Teile dieser Arbeit wurden als Vortrag auf der Jahrestagung der DGP in Bad Reichenhall 1999 vorgestellt.

Literatur

  • 1 Bonner J A, Sloan J A, Hillman S H. et al . A quality-adjusted re-analysis of a phase III trial comparing once-daily thoracic radiation therapy versus twice-daily thoracic radiation therapy in patients with limited stage small cell lung cancer.  Proc ASCO. 1999;  18 1799
    PubMedGoogle Scholar
  • 2 Bunn P A, Lichter A S, Makuch R W. et al . Chemotherapy alone or chemotherapy with chest radiotherapy in limited stage small cell lung cancer.  Ann Intern Med. 1987;  106 655-662
    PubMedGoogle Scholar
  • 3 Bunn P A, Crowley J, Kelly K. et al . Chemoradiotherapy with or without GM-CSF in the treatment of limited stage small cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group.  JCO. 1995;  13,/ 1632-1641
    PubMedGoogle Scholar
  • 4 Choi N C, Carey R W. Importance of radiation dose in achieving improved locoregional tumor control in limited-stage small-cell lung carcinoma.  Int J Radiat Oncol Biol Phys. 1989;  17 307-310
    PubMedGoogle Scholar
  • 5 Coy P, Hodson I, Payne D G. et al . The effect of dose of thoracic irradiation on recurrence in patients with limited stage small cell lung cancer: inital results of a Canadian multicenter randomized trial.  Int J Radiat Oncol biol Phys. 1988;  14 219-226
    PubMedGoogle Scholar
  • 6 Gatzemeier U, Hossfeld D K, Neuhauss R. et al . Phase II and III studies with carboplatin in small cell lung cancer.  Semin Oncol. 1992;  19 S 2 28-36
    PubMedGoogle Scholar
  • 7 Goodman G E, Crowley J J, Blasko J C. et al . Treatment of limited small cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin and cyclophosphamide and chest radiotherapy: A Southwest Oncology Group Study.  JCO. 1990;  8, 1 39-47
    PubMedGoogle Scholar
  • 8 Goto K, Nishiwaki Y, Takada M. et al . Final results of a phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited stage small cell lung cancer (LD-SCLC): The Japan clinical oncology group (JCOG).  Proc ASCO. 1999;  18 1805
    PubMedGoogle Scholar
  • 9 Gregor A, Drings P, Burghouts J. et al . Randomized trial of alternating versus sequential radiotherapy/chemotherapy in limited disease patients with SCLC: A EORTC study.  JCO. 1997;  15(8) 2840-2849
    PubMedGoogle Scholar
  • 10 Gregor A, Cull A, Stephens R J. et al . Prophylactic cranial irradiation is indicated following complete response to induction therapy in small cell lung cancer: Results of a multicentric randomised trial.  Eur J Canc. 1997;  33,11 1752-1758
    PubMedGoogle Scholar
  • 11 Gridelli C, D'Aprile M, Curcio C. et al . Carboplatin plus epirubicin plus VP-16, concurrent “split course” radiotherapy and adjuvant surgery for limited small cell lung cancer.  Lung Cancer. 1994;  11 83-91
    PubMedGoogle Scholar
  • 12 Ihde D, Souhami B, Comis R. et al . Consensus report small cell lung cancer.  Lung Cancer. 1997;  17 S S19-S21
    CrossrefPubMedGoogle Scholar
  • 13 Jeremic B, Shibamoto Y, Acimovic L, Milisavljevic S. Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small-cell lung cancer: a randomized study.  JCO. 1997;  15; 3 893-900
    PubMedGoogle Scholar
  • 14 Jeremic B, Shibamoto Y, Acimovic L, Milisavlevis S. Carboplatin, Etoposide and accelerated hyperfractionated radiotherapy for elderly patients with limited small cell lung carcinoma.  Cancer. 1998;  82; 5 836-841
    CrossrefPubMedGoogle Scholar
  • 15 Johnson D H, Bass D, Einhorn L H. et al . Combination chemotherapy with or without thoracic radiotherapy in limited-stage small cell lung cancer: a randomized trial of the Southeastern Cancer Study Group.  JCO. 1993;  11, 7 1223-1229
    PubMedGoogle Scholar
  • 16 Johnson B E, Bridges J D, Sobczeck M. et al . Patients with limited-stage small-cell lung cancer treated with concurrent twice-daily chest radiotherapy and etoposide/cisplatin followed by cyclophosphamide, doxorubicin and vincristine.  J Clin Oncol. 1996;  14 806-813
    PubMedGoogle Scholar
  • 17 Koch K, Broll I, Cordes G. et al . Strahlentherapie der Bronchialkarzinome.  Atemw.-Lungenkrankheiten. 1987;  13, 3 81-87
    PubMedGoogle Scholar
  • 18 Kosmidis P A, Samantas E, Fountzilas G. et al . Cisplatin/etoposide versus carboplatin/etoposide chemotherapy and irradiation in small cell lung cancer: a randomized phase III study.  Semin Oncol. 1994;  21 S3 23-30
    PubMedGoogle Scholar
  • 19 Kristjansen P EG, Hansen H H. Prophylactic cranial irradiation in small cell lung cancer - an update.  Lung cancer. 1995;  12, S3 S23-S40
    PubMedGoogle Scholar
  • 20 Kubota K, Itoh R, Kodama T. et al . Concurrent cisplatin/etoposide (PE) and twice-daily thoracic radiotherapy (BID TRT) followed by weekly dose intensive regimen (CODE) with human granulocyte-colony stimulating factor (G-CSF) for limited-stage small cell lung cancer.  Proc ASCO. 1999;  18 1978
    PubMedGoogle Scholar
  • 21 Maurer L H, Herndon J E, Hollis D R. et al .Randomized trial of chemotherapy and radiation therapy with or without Warfarin for limited-stage small cell lung cancer: a Cancer and Leukemia Group B study. 
  • 22 Meropol J J, Miller L L, Korn E L. Severe myelosuppression resulting from concurrent administration of granulocyte colony stimulating factor and cytotoxic chemotherapy.  J Natl Cancer Inst. 1992;  84 1201-1202
    PubMedGoogle Scholar
  • 23 Miller A B, Hoogsstraten B, Staquet M, Winkler A. Reporting results of cancer treatment.  Cancer. 1981;  47 207-214
    CrossrefPubMedGoogle Scholar
  • 24 Murray N, Coy P C, Pater J L. et al . Importance of timing for thoracic irradiation in the combined modality treatment of limited stage small cell lung cancer.  JCO. 1993;  11; 2 336-344
    PubMedGoogle Scholar
  • 25 National Cancer Institute: NCI .Investigator's Handbook. A manual for participants in clinical trials of investigational agents. Cancer therapy evaluation program. Division of cancer treatment, National Cancer Institute, Bethesda. Maryland (USA); 1993
  • 26 Perry M C, Eaton W L, Propert K J. et al . Chemotherapy with or without radiation therapy in limited small cell carcinoma of the lung.  N Engl J Med. 1987;  3316 912-918
    PubMedGoogle Scholar
  • 27 Pignon J P, Arriagada R, Idhe D C. et al . A meta-analysis of thoracic radiotherapy for SCLC.  NEJM. 1992;  327, 23 1618-1624
    CrossrefPubMedGoogle Scholar
  • 28 Salazar O M, Slawson R G, Pouissin-Rosillo H. et al . A prospective randomized trial comparing once-a-week vs. daily radiation therapy for locally-advanced non-metastatic lung cancer.  Int J Rad Oncol Biol Phys. 1986;  12 779-787
    PubMedGoogle Scholar
  • 29 Serke M, Lienert T, Bender J. et al . Lung cancer: Clinical data from a 10 years registry.  ERJ. 1998;  12, 307S P2045
    PubMedGoogle Scholar
  • 30 Turrisi A, Kyungmann K, Blum R B. et al . Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide.  NEJM. 1999;  340, 4 265-271
    CrossrefPubMedGoogle Scholar
  • 31 Warde P, Payne D. Does thoracic radiation improve survival and local control in limited-stage small cell carcinoma of the lung.  J Clin Oncol. 1992;  10 890-895
    CrossrefPubMedGoogle Scholar
  • 32 Work E, Nielsen O S, Bentzen S. et al . Randomized study of initial versus late chest irradiation combined with chemotherapy in limited stage small cell lung cancer.  JCO. 1997;  15, 9 3030-3037
    PubMedGoogle Scholar

1 Teile dieser Arbeit wurden als Vortrag auf der Jahrestagung der DGP in Bad Reichenhall 1999 vorgestellt.

Dr. med. Monika Serke

Lungenklinik Heckeshorn, Pneumologie II

Zum Heckeshorn 33

14109 Berlin