Zusammenfassung
Einleitung
Die Qualität der adjuvanten Chemotherapie beim Mammakarzinom ist von genereller Bedeutung seit die Aufrechterhaltung der absoluten Dosis und der totalen Dosisintensität der verabreichten Chemotherapie das Überleben der Patientinnen beeinflusst.
Patientinnen und Methodik
Diese retrospektive Analyse schließt 175 Patientinnen ein, die im Zeitraum von 1991 - 1999 an sechs Kliniken in Deutschland wegen eines primären Mammakarzinoms adjuvant systemisch behandelt wurden. Die Datenerhebung erfolgte anhand der Krankenblätter. Zur Auswertung kamen die Art der Behandlung, die jeweiligen im Chemotherapieregime enthaltenen Zytostatika, sowohl die geplanten als auch die tatsächlich verabreichten Dosierungen und der Zeitpunkt der Applikation. Ebenso wurden die hämatologischen und nicht hämatologischen Nebenwirkungen und das Ausmaß der supportiven Therapie erfasst.
Ergebnisse
Im Beobachtungszeitraum kamen 18 verschiedene Chemotherapieregime zur Anwendung. Eine CMF-haltige Chemotherapie erhielten 110 Patientinnen (62 %), eine anthrazyklinhaltige Chemotherapie erhielten dagegen 65 Patientinnen (38 %). Von den 915 auszuwertenden Therapiezyklen wurden 870 Zyklen (95 %) effektiv verabreicht. Eine Therapieverschiebung von mehr als 7 Tagen erfolgte bei 100 Zyklen (11,5 %). Eine Dosisreduktion um mehr als 15 % erfolgte in 20 Fällen (2,3 %). Als relevanter Faktor für die Reduktion der relativen totalen Dosisintensität ergab sich der Zeitpunkt der Strahlentherapie, insbesondere wenn die Strahlentherapie vor oder während der Chemotherapie erfolgte (p = 0,05).
Schlussfolgerungen
Im Vergleich mit einer anthrazyklinhaltigen Chemotherapie ist eine CMF-haltige Chemotherapie mit einer größeren Anzahl von Dosiskompromissen bei der Behandlung außerhalb von klinischen Studien in der adjuvanten Situation verbunden (p = 0,02). Bei der Festlegung der interdisziplinären Therapieplanung von primären Mammakarzinomen ist ein besonderes Augenmerk auf die zeitliche Interaktion von Chemotherapie und Strahlentherapie zu legen.
Abstract
Background
The quality of adjuvant chemotherapy is of general interest since maintenance of total dose and total dose intensity of chemotherapy delivered influences clinical outcome.
Patients and Methods
This retrospective analysis evaluated 175 patients treated for primary breast cancer outside the setting of a clinical trial in six German centres from 1991 to 1999. The data retrieved from the patients' files were analysed for treatment types, drugs given per regimen with planned and delivered doses of the drugs, dates of dose delivery, haematological and non-haematological toxicities and amount and duration of supportive therapy.
Results
A total of 18 different schedules was recorded. 110 patients (62 %) received a CMF-type regime and 65 patients (38 %) an anthracycline-based protocol. Of the 915 total cycles 870 (95 %) were effectively administered. Of the delivered cycles 100 (11.5 %) were delayed by > 7 days and 20 (2.3 %) had dose reductions of > 15 %. An important influencing factor on relative total dose intensity was the concomitant radiation administered before or during chemotherapy (p = 0.05).
Conclusions
CMF-type regimens were likely to have more dose delays compared to anthracycline-based regimens (p = 0.02) if used in the adjuvant setting. If chemotherapy is applied in combination with radiation special caution is mandatory to ensure maintenance of the delivered dose intensity.
Schlüsselwörter
Adjuvante Therapie - Mammakarzinom - Dosisintensität - hämatopoetische Wachstumsfaktoren - Strahlentherapie
Key words
Adjuvant therapy - breast cancer - dose intensity - haematopoietic growth factors - radiation
References
1
Jemal A, Thomas A, Murray T. et al .
Cancer Statistics, 2002.
CA Cancer J Clin.
2002;
52
23-47
2
Nab H W, Hop W C, Crommelin M A, Kluck H M, Coebergh J W.
Improved prognosis of breast cancer since 1970 in south-eastern Netherlands.
Br J Cancer.
1994;
70
285-288
3
Young R C.
Cancer Statistics, 2002: Progress or cause of concern.
CA Cancer J Clin.
2002;
52
6-7
4
Early Breast Cancer Trialists Collaborative Group ( EBCTCG).
Polychemotherapy for early breast cancer: an overview of the randomised trials.
Lancet.
1998;
352
930-942
5
Chu K C, Tarone R E, Kessler L G, Ries L AG, Hankey B F, Miller B A, Edwards B K.
Recent trends in US breast cancer: incidence, survival and mortality rates.
J Natl Cancer Inst.
1996;
88
1571-1579
6
Corry J F, Lonning P E.
Systemic therapy in breast cancer: efficacy and cost utility.
Pharmaco Economics.
1994;
3
198-212
7
Hryniuk W, Levine M N.
Analysis of dose intensity for adjuvant chemotherapy trials in stage II breast cancer.
J Clin Oncol.
1986;
4
1162-1170
8
Wood W C, Budman D R, Korzun A H. et al .
Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma.
N Engl J Med.
1994;
330
1253-1259
9
Budman B D, Berry D A, Cirrincione C T. et al .
Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer.
J Natl Cancer Inst.
1998;
90
1205-1211
10
van Tongelen K, Steward W, Blackledge G. et al .
EORTC joint ventures in quality control: treatment related variables and data acquisition in chemotherapy trials.
Eur J Cancer.
1991;
27
201-207
11
Ottevanger P B, Verhagen C AHHVM, Beex L VAM.
Quality of adjuvant chemotherapy in primary breast cancer in a non-trial setting. A comprehensive cancer center study.
Eur J Cancer.
1999;
35
386-391
12
Lomas J, Anderson G M, Domnick-Pierre K. et al .
Do practice guidelines guide practice?.
New Engl J Med.
1989;
321
1306-1311
13
Saarto T, Blomqvist C, Rissanen P, Auvinen A, Elomaa I.
Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer.
Br J Cancer.
1997;
75
301-305
14
Crawford J, Ozer H, Toller R. et al .
Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer.
N Engl J Med.
1991;
315
164-170
15
Ozer H, Armitage J O, Bennett C L. et al .
2000 Update of recommendations for the use of hematopoetic colony-stimulating factors: Evidence-based, clinical practice guidelines.
J Clin Oncol.
2000;
17
3558-3585
16
Silber J H, Fridman M, Shpilsky A, Even-Shashan O, Smink D S, Jayaraman J, Fox K R, Pauly M V.
Modeling the cost-effectiveness of granulocyte colony-stimulating factor use in early-stage breast cancer.
J Clin Oncol.
1998;
16
2435-2444
17
Silber J H, Fridman M, DiPaola R S, Erder M H, Pauly M V, Fox K R.
First-cycle blood counts and subsequent neutropenia, dose reduction, or delay in early-stage breast cancer therapy.
J Clin Oncol.
1998;
16
2392-2400
18
Bonadonna G, Valagussa P, Moliterni A.
Zambetti M, Brambilla C. Adjuvant cyclophosphamide, methotrexate and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up.
N Engl J Med.
1995;
332
901-906
19
Goldhirsch A, Glick J H, Gelber R D. et al .
Meeting highlights: International panel on the treatment of primary breast cancer.
J Natl Cancer Inst.
1998;
90
1601-1608
20
Goldhirsch A, Glick J H, Gelber R D. et al .
Meeting highlights: International panel on the treatment of primary breast cancer.
J Clin Oncol.
2001;
19
3817-3827
21
Recht A, Come S E, Henderson I C. et al .
The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer.
N Engl J Med.
1996;
334
1356-1361
22
Paridaens R J, Lemmens J, Devadder N. et al .
Influence of concomitant radiotherapy on dose intensity of adjuvant CMF in patients with node positive breast cancer.
Eur J Cancer.
1995;
31 A (Suppl 5)
S12
23
Overgaard M, Hansen P S, Overgaard J. et al .
Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy.
N Engl J Med.
1997;
337
949-955
24
Ragaz J, Jackson S M, Le N. et al .
Adjuvant radiotherapy and chemotherapy in node positive premenopausal women with breast cancer.
N Engl J Med.
1997;
337
956-962
25
Janni W, Dimpfl T, Knobbe A, Strobl B, Rjosk D, Willgeroth F, Genz T.
Risk of local recurrence of breast cancer and irradiation of the chest wall.
Geburtsh Frauenheilk.
2000;
60
130-138
26
Trillet-Lenoir V, Green J, Manegold C. et al .
Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy.
Eur J Cancer.
1993;
29 A
319-324
27
Lyman G H, Lyman C G, Sanderson R A, Balducci L.
Decision analysis of hematopoietic growth factor use in patients receiving cancer chemotherapy.
J Natl Cancer Inst.
1993;
85
488-493
28
Gant M.
Impact of participation in randomized clinical trials on survival of women with early-stage breast cancer: An analysis of 7985 patients.
Proc Am Soc Oncol.
2000;
19
74a-(abstr. 287)
29
du Bois A, Pfisterer J, Kellermann L, Kreienberg R.
Treatment of advanced ovarian cancer in Germany: The impact of participation in clinical trials.
Geburtsh Frauenheilk.
2001;
61
863-871
30
Kühn T, Vogl F D, Santjohanser C, Kotzerke J. et al .
Sentinel-node-biopsy in breast cancer - Results from a multicenter trial.
Geburtsh Frauenheilk.
2001;
61
376-383
Appendix A
Department of Gynaecology and Obstetrics, University Hospital Muenster, Germany
Women's Clinic Raphaelsklinik Muenster, Germany
Women's Clinic Johanna-Etienne Hospital Neuss, Germany
Clinic of Haematology, Municipal Hospital Guetersloh, Germany
Women's Clinic vom Roten Kreuz Munich, Germany
Clinic of Haematology Paracelsusklinik Osnabrueck, Germany
Priv.-Doz. Dr. med. Christian Jackisch
Department of Gynecology, Gynecologic Endocrinology and Oncology Philipps-University Marburg
Pilgrimstein 3
35037 Marburg
Germany
eMail: jackisch@med.uni-marburg.de