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Strahlentherapie und Onkologie

, Volume 185, Issue 9, pp 582–587 | Cite as

Concomitant Radiochemotherapy of Cervical Cancer

Is It Justified to Reduce the Dosage of Cisplatin?
  • Mihály Patyánik
  • Csaba Nemeskéri
  • Zsuzsa Póti
  • Dániel Sinkó
  • Csilla Pesznyák
  • Réka Király
  • Róbert Kois
  • Árpád MayerEmail author
Original Article

Purpose:

To review the experiences regarding the therapeutic response and side effects of concomitant radiochemotherapy of cervical cancer carried out with different cisplatin doses.

Patients and Methods:

At the Municipal Center for Oncoradiology, Budapest, Hungary, 92 patients with cervical cancer were treated with concomitant radiochemotherapy in the period between July 2002 and March 2007. The total dose of high-energy external radiation (megavoltage) treatment was 50.4 Gy with a fraction dose of 1.8 Gy on the small pelvis. Before irradiation, cisplatin 40 mg/m2, 30 mg/m2, or 20 mg/m2 was administered once a week.

Results:

In 17 cases, the cisplatin dose was 30 mg/m2; during radiochemotherapy the number of cisplatin treatments was equal to or more than four in 14 patients (82%). After administering 40 mg/m2 cisplatin to 64 patients, chemotherapy in four or more treatments could only be applied in 37 cases (58%). Eleven patients received cisplatin at the dose of 20 mg/m2; in ten (91%) of them, the number of treatments was four or more. By comparing the side effects, it can be stated that hematologic side effects (mostly leukopenia) grade 3 occurred in 12% of the patients receiving cisplatin 30 mg/m2, and grade G3–4 in 16% of the 40-mg/m2 cisplatin group. For cisplatin 30 mg/m2, 82% of hematologic side effects were in the G1 range. There was no significant difference between the 20- and 30-mg/m2 regimens. As for the gastrointestinal toxicity, similar side effects grade 1 were detected, which occurred in 58% and 38% of the patients receiving 30 mg/m2 and 40 mg/m2, respectively.

Conclusion:

On the basis of a detailed analysis, the correlation between the number of treatments, the therapeutic and the side effects could be verified. In the course of dose reduction, there was no significant difference when comparing the results of therapy, however, the quality of life was better if cisplatin 30 mg/m2 was administered instead of 40 mg/m2. If cisplatin 20 mg/m2 was given, the results were significantly worse. On the basis of the own results, it can be stated that the optimal weekly dose of cisplatin is 30 mg/m2.

Key Words:

Cervical cancer Radiochemotherapy Toxicity 

Radiochemotherapie des Zervixkarzinoms. Kann die Cisplatindosis reduziert werden?

Ziel:

Reduktion der Cisplatindosis bei der Radiochemotherapie des Zervixkarzinoms in Abhängigkeit von therapeutischen Effekten und Nebenwirkungen.

Patienten und Methodik:

Zwischen Juli 2002 und März 2007 erhielten 92 Patientinnen mit Zervixkarzinom am Städtischen Onkoradiologischen Zentrum, Budapest, Ungarn, eine Radiochemotherapie. Das kleine Becken wurde mit einer Gesamtdosis von 50,4 Gy (28 Fraktionen à 1,8 Gy) bestrahlt. Vor der Radiotherapie wurde Cisplatin wöchentlich in einer Dosierung von einmal 40 mg/m2, 30 mg/m2 oder 20 mg/m2 Körperoberfläche gegeben.

Ergebnisse:

17 Patientinnen erhielten zusätzlich zur Radiotherapie 30 mg/m2 Cisplatin, 14 von ihnen (82%) tolerierten vier oder mehr Cisplatinapplikationen. In der Gruppe mit 40 mg/m2 Cisplatin vertrugen nur 37 Patientinnen (58%) vier oder mehr Cisplatinapplikationen. In der dritten Gruppe (elf Patientinnen) erhielten zehn Patientinnen (91%) vier oder mehr Cisplatinbehandlungen mit 20 mg/m2/Woche. Beim Vergleich der Nebenwirkungen konnte festgestellt werden, dass hämatologische Nebenwirkungen (meist Leukopenie) Grad 3 bei 12% der Gruppe mit 30 mg/m2 und Grad 3–4 bei 16% der Gruppe mit 40 mg/m2 Cisplatin auftraten. 82% der hämatologischen Nebenwirkungen unter 30 mg/m2 Cisplatin wurden als Grad 1 eingestuft. Es konnte kein Unterschied zwischen den Schemata mit 20 und 30 mg/m2 gefunden werden. Bezüglich der gastrointestinalen Toxizität wurden ebenfalls Grad-1-Nebenwirkungen beobachtet, die bei 30 mg/m2 in 58% und bei 40 mg/m2 in 38% auftraten.

Schlussfolgerung:

Die optimale wöchentliche Dosierung für Cisplatin beträgt 30 mg/m2. Zwischen der kumulativen Cisplatindosis und der therapeutischen Effektivität besteht eine deutliche Korrelation. 40 mg/m2 erhöhten die therapeutische Wirkung nicht. Die Lebensqualität der Patientinnen war aber bei kleineren Dosen besser. 20 mg/m2 Cisplatin ergaben signifikant schlechtere Resultate.

Schlüsselwörter:

Zervixkarzinom Radiochemotherapie Toxizität 

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References

  1. 1.
    Ang KK. Concurrent radiation chemotherapy for locally advanced head and neck carcinoma: are we addressing burning subjects? J Clin Oncol 2004;22:4607–59.CrossRefGoogle Scholar
  2. 2.
    Arriagada R, Goldstraw P, Le Chevalier T. Management of non-small-cell lung cancer. In: Souhami RL, Tannock I, Hohenburger P, et al., eds. Oxford textbook of oncology, 2nd edn. Oxford-New York: Oxford University Press, 2002:2089–110.Google Scholar
  3. 3.
    Bese NS, Hendry J, Jeremic B. Effect of prolongation of overall treatment time due to unplanned interruption during radiotherapy of different tumour sites and practical methods for compensation. Int J Radiat Oncol Biol Phys 2007;68:654–61.PubMedGoogle Scholar
  4. 4.
    Dellas K, Bache M, Pigorsch SU, et al. Prognostic impact of HIF-1 alfa expression in patients with definitive radiotherapy for cervical cancer. Strahlenther Onkol 2008;184:169–74.PubMedCrossRefGoogle Scholar
  5. 5.
    Dörr W, Köst S, Keinert K, et al. Early intestinal changes following abdominal radiotherapy. Comparison of endpoints. Strahlenther Onkol 2006;182:1–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Eifel PJ, Rose PG. Chemotherapy and radiation therapy for cervical cancer. In: ASCO 2000 educational book. Alexandria: ASCO, 2000:199–206.Google Scholar
  7. 7.
    Füller J, Guderian D, Köhler C, et al. Lymph edema of the lower extremities after lymphadenectomy and radiotherapy for cervical cancer. Strahlenther Onkol 2008;184:206–11.PubMedCrossRefGoogle Scholar
  8. 8.
    Hreshchyshyn MM, Aron BS, Boronow RC, et al. Hydroxyurea or placebo combined with radiation to treat stages IIB and IV cervical cancer confined to the pelvis. Int J Radiat Oncol Biol Phys 1979;5:317–72.PubMedGoogle Scholar
  9. 9.
    Ikushima H, Osaki K, Furutan S, et al. Chemoradiation therapy for cervical cancer: toxicity of concurrent weekly cisplatin. Radiat Med 2006;24:115–21.PubMedCrossRefGoogle Scholar
  10. 10.
    Keys HM, Bundy BN, Stehman FB, et al. Cisplatin, radiation, and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med 1999;340:1154–61.PubMedCrossRefGoogle Scholar
  11. 11.
    Marnitz S, Köhler C, Füller J, et al. Uterus necrosis after radiochemotherapy in two patients with advanced cervical cancer. Strahlenther Onkol 2006;182:45–51.PubMedCrossRefGoogle Scholar
  12. 12.
    Marnitz S, Köhler C, Roth C, et al. Stage-adjusted chemoradiation in cervical cancer after transperitoneal laparoscopic staging. Strahlenther Onkol 2007;183:473–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Marnitz S, Köhler C, Schneider A, et al. Interindividual variability of lymph drainages in patients with cervical cancer. Implication on irradiation planning. Strahlenther Onkol 2006;185:80–5.CrossRefGoogle Scholar
  14. 14.
    Mayer Á. Brachyterápia tegnap és ma. Magy Onkol 1998;42:5–8.Google Scholar
  15. 15.
    Mayer Á. Radioterápia az ezredfordulón. Orv Hetil 1999;140:1875–80.PubMedGoogle Scholar
  16. 16.
    Mayer Á, Nemeskeri C, Petnehazi C, et al. Primary radiotherapy of stage IIA/B-IIIB cervical carcinoma. A comparison of continuous versus sequential regimens. Strahlenther Onkol 2004;180:209–15.PubMedCrossRefGoogle Scholar
  17. 17.
    Morris M, Eifel PJ, Lu J, et al. Pelvic radiation with concurrent chemotherapy compared with pelvic and paraaortic radiation for high-risk cervical cancer. N Engl J Med 1999;340:1137–43.PubMedCrossRefGoogle Scholar
  18. 18.
    Nagy V, Coza O, Ordeanu C, et al. Radiotherapy versus concurrent 5-day cisplatin and radiotherapy in locally advanced cervical carcinoma. Strahlenther Onkol 2008;185:177–83.CrossRefGoogle Scholar
  19. 19.
    National Cancer Institute. Clinical announcement. Bethesda: United States Department of Health and Human Services, Public Health Service, February 1999.Google Scholar
  20. 20.
    National Cancer Institute Common Terminology Criteria for Adverse Events v 3.0 (CTCAE). Cancer therapy evaluation program. Bethesda, MD, USA: NCI, 2003 http://ctep.cancer.gov Google Scholar
  21. 21.
    Ohara K, Tanaka YO, Tsunoda H, et al. Preliminary estimation of treatment effect on uterine cervical squamous cell carcinoma in terms of tumor regression rate: comparison between chemoradiotherapy and radiotherapy alone radiation. Radiat Med 2005;23:25–9.PubMedGoogle Scholar
  22. 22.
    Perez CA, Brady LW. Late radiation morbidity scoring criteria RTOG/EORTC. In: Perez CA, Brady LW, eds. Priciples and practice of radiation oncology, 2nd edn. Philadelphia: Lippincott, 1993:53–5.Google Scholar
  23. 23.
    Peters WAI, Liu PY, Barrett R, et al. Cisplatin, 5-fluorouracil plus radiation therapy are superior to radiation therapy as adjunctive therapy in high-risk, early-stage carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy. Report of phase III Intergroup Study. Gynecol Oncol 1999;72:443.abstract.CrossRefGoogle Scholar
  24. 24.
    Póti Z, Patyánik M, Nemekéri C. Méhnyakrák radiochemoterápiája (kemoterápiás dózisredukció szükségessége). Orv Hetil 2006;147:1315–20.PubMedGoogle Scholar
  25. 25.
    Rose PG, Bundy BN, Watkins EB, et al. Concurrent cisplatin-based chemotherapy and radiotherapy for locally advanced cervical cancer. N Engl J Med 1999;340:1144–53.PubMedCrossRefGoogle Scholar
  26. 26.
    Schaake-Koning C, Bartelnink H, Adema BH, et al. Radiotherapy and cisdiammine dichloroplatinium (II) as a combined treatment modality for inoperable non-small cell lung cancer: a dose finding study. Int J Radiat Oncol Biol Phys 1986;12:379–83.PubMedGoogle Scholar
  27. 27.
    Shepherd JH. Staging announcement FIGO staging of gynecologic cancers: cervical and vulva. Int J Gynecol Cancer 1995;5:319.Google Scholar
  28. 28.
    Souhami L, Seymour R, Roman TN, et al. Weekly cisplatin plus external beam radiotherapy and high dose rate brachytherapy in patients with locally advanced carcinoma of the cervix. Int J Radiat Oncol Biol Phys 1993;27:871–8.PubMedGoogle Scholar
  29. 29.
    Sterzing F, Grehn C, Dinkel J. Severe reversible toxic encephalopathy induced by cisplatin in a patient with cervical carcinoma receiving combined radiochemotherapy. Strahlenther Onkol 2007;183:487–9.PubMedCrossRefGoogle Scholar
  30. 30.
    van der Zee J, Gonzalez Gonzalez D, van Rhoon GC, et al. Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group. Lancet 2000;355:1119–25.PubMedCrossRefGoogle Scholar
  31. 31.
    Varveris H, Kachris S, Mazonakis M, et al. Phase I/II trial of external irradiation plus medium-dose brachytherapy given concurrently to liposomal doxorubicin and cisplatin for advanced uterine cervix carcinoma. Strahlenther Onkol 2006;182:125–34.PubMedCrossRefGoogle Scholar
  32. 32.
    Whitney CW, Sause W, Bundy BN, et al. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stages IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol 1999;17:1339–48.PubMedGoogle Scholar

Copyright information

© Urban & Vogel, Muenchen 2009

Authors and Affiliations

  • Mihály Patyánik
    • 1
  • Csaba Nemeskéri
    • 1
  • Zsuzsa Póti
    • 1
  • Dániel Sinkó
    • 1
  • Csilla Pesznyák
    • 1
  • Réka Király
    • 1
  • Róbert Kois
    • 2
  • Árpád Mayer
    • 1
    • 3
    Email author
  1. 1.Center for OncoradiologyMunicipal Uzsoki HospitalBudapestHungary
  2. 2.St. Stephen and St. Leslie United Hospital of the Municipal GovernmentBudapestHungary
  3. 3.Center for OncoradiologyMunicipal Uzsoki HospitalBudapestHungary

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