Advertisement

Revista de Oncología

, Volume 4, Issue 5, pp 250–254 | Cite as

Cisplatin-based chemotherapy and hyperfractionated radiotherapy for stage III non-small cell lung cancer: survival and patterns of failure after long follow-up

  • Martín Tejedor GutiérrezEmail author
  • Juan José Valerdi Álvarez
  • Begoña Bermejo Fraile
  • Juan Ignacio Arraras Urdaniz
  • Ruth Vera García
  • Francisco Molina Rosillo
  • Juan José Albistur Tomé
Originales
  • 18 Downloads

Abstract

The main purpose of this prospective non randomized trial was to analyse whether induction chemotherapy and hyperfractionated radiotherapy combined with cisplatin can improve the long-term survival of patients with locally advanced non small cell lung cancer.

From 1992 to 1995, 70 patients received the programmed treatment scheme with: one cycle of induction chemotherapy with mitomycin 10 mg/m2/day 1, cisplatin 100 mg/m2 day 1 and vindesine 3 mg/m2/days 1, 8 and 15, followed after 4 weeks of hyperfractionated radiotherapy (1.2 Gy twice/day, five days per week, until total dose of 69.6 Gy) concomitant with cisplatin 20 mg/m2/day by continuous infusion, for 5 days in the first and fifth weeks of radiotherapy. Patients with stage IIIA, good performance status and radiological partial response were candidated to surgical rescue.

Thirty-two patients (45.7%) developed severe toxicity (WHO grade 5–4). Complete radiological response was observed in 9 patients (12.8%). Overall median survival time was 14 months, 2-year survival of 20% and 5-year survival of 12%. The cause of dead was by local progression in 42%, distant metastases in 40%, simultaneous relapse in 10% and intercurrent disease in 8%. Patients with stage IIIA (n=16, 7 with surgical rescue) had a 5-year survival of 52%, and patients with stage IIIB (n=54) of 6%.

Long-term results with this treatment scheme are disappointing, only patients with stage IIIA and surgical rescue showed an improvement on survival. In spite of chemotherapy and high radiation dose, local-regional progression and distant metastases remain significant patterns of failure and dead of these patients.

Key words

lung cancer non-small cell stage III cisplatin hyperfractionated radiotherapy long-term results 

Quimioterapia basada en cisplatino y radioterapia hiperfraccionada en carcinoma de pulmón no microcítico estadio III: supervivencia y patrón de recaída tras seguimiento a largo plazo

Resumen

El objetivo principal de este estudio no aleatorizado fue investigar si la combinación de quimioterapia de inducción con radioterapia hiperfraccionada asociada a cisplatino puede mejorar la supervivencia a largo plazo de los pacientes con carcinoma de pulmón no microcítico en estadio localmente avanzado.

Entre 1992 y 1995, 70 pacientes recibieron el esquema de tratamiento programado con un ciclo de quimioterapia de inducción con mitomicina 10 mg/m2/día 1, cisplatino 100 mg/m2 día 1 y vindesina 3 mg/m2 días 1, 8 y 15, administrando 4 senmanas después la radioterapia hiperfraccionada (1,2 Gy sesión/dos veces día, 5 días por semana, hasta dosis total de 69,6 Gy) concomitante con cisplatino 20 mg/m2/día en infusión continua, durante 5 días en la primera y quinta semana de la radioterapia. Los pacientes con estadio IIIA, buen estado general y respuesta parcial radiológica fueron candidatos paracirugía de rescate.

Treinta y dos pacientes (45,7%) presentaron toxicidad severa (grados 5–4 de la Organización Mundial de la Salud [OMS]). Se observó respuesta radiológica completa en 9 pacientes (12,8%). La mediana de supervivencia global fue de 14 meses, la supervivencia a dos años del 20% y a 5 años del 12%. La causa de muerte fue progresión local en 42%, metástasis a distancia en 40%, recaída simultánea en 10% y enfermedad intercurrente en 8%. Los pacientes con estadio IIIA (n=16,7 con cirugía de rescate) tuvieron una supervivencia a 5 años del 52% y los pacientes con estadio IIIB (n=54) del 6%.

Los resultados a largo plazo con este esquema terapéutico son desalentadores, sólo los pacientes con estadio IIIA y rescate quirúrgico mostraron un incremento en la supervivencia. A pesar de la quimioterapia y altas dosis de radiación, la progresión locorregional y las metástasis a distancia continúan siendo las principales causas de recaída y muerte en estos pacientes.

Palabras clave

cáncer de pulmón no microcítico estadio III cisplatino radioterapia hiperfraccionada resultados a largo plazo 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    LeChevalier T, Arrigada R, Quoix E, et al. Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small cell lung cancer: first analysis of a randomized trial in 353 patients. J Natl Cancer Inst 1991;83:417–23.CrossRefGoogle Scholar
  2. 2.
    Schaake-Koning C, van den Bogaert W, Dalesio O, et al. Effects of concomitant cisplatin and radiotherapy on inoperable non-small cell lung cancer. N Engl J Med 1992;326:524–30.CrossRefPubMedGoogle Scholar
  3. 3.
    Tejedor M, Valerdi J, Lopez R, et al. Mitomycin, cisplatin, and vindesine followed by radiotherapy combined with cisplatin in stage III non-small cell lung cancer: long-term results. Int J Radiat Oncol Biol Phys 1995;31:813–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Cox JD, Azarnia N, Byhardt RW, et al. A randomised phase I/II trial of hyperfractionated radiation therapy with total doses of 60.0 Gy to 79.2 Gy: possible survival benefit with total greater than or equal to 69.6 Gy in favourable patients with Radiation Therapy Oncology Group stage III non-small cell lung carcinoma; report of Radiation Therapy Oncology Group 83.11. J Clin Oncol 1990;8:1543–55.PubMedGoogle Scholar
  5. 5.
    Kaplan EL, Meier P. Non parametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457–81.CrossRefGoogle Scholar
  6. 6.
    Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 1966;50:163–70.PubMedGoogle Scholar
  7. 7.
    Eberhardt W, Wilke H, Stamatis G, et al. Preoperative chemotherapy followed by concurrent chemoradiation therapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non-small-cell lung cancer: mature results of a phase II trial. J Clin Oncol 1998;16:622–34.PubMedGoogle Scholar
  8. 8.
    Thomas M, Rube C, Semik M, et al. Impact of preoperative bimodality induction including twice-daily radiation on tumor regression and survival in Stage III non-small-cell lung cancer. J Clin Oncol 1999;17:1185–95.PubMedGoogle Scholar
  9. 9.
    Fowler WC, Langer CJ, Curran WJ Jr, et al. Postoperative complications after combined neoadjuvant treatment of lung cancer. Ann Thorac Surg 1993;55:986–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Lochrin C, Goss G, Stewart, DJ, et al. Concurrent chemotherapy with hyperfractionated accelerated thoracic irradiation in stage III non-small cell lung cancer. Lung Cancer 1999;23:19–30.CrossRefPubMedGoogle Scholar
  11. 11.
    Lopez-Picazo JM, Azinovic I, Aristu JJ, et al. Induction platinum-based chemotherapy followed by radical hyperfractionated radiotherapy with concurrent chemo-therapy in the treatment of locally advanced non-small-cell carcinoma of the lung. Am J Clin Oncol 1999;22:203–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Sause W, Kolesar P, Taylor S, et al. Final results of Phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group and Southwest Oncology Group. Chest 2000;117:358–64.CrossRefPubMedGoogle Scholar
  13. 13.
    Saunders MI, Dische S, Barrett A, et al. Randomized multicenter trials of CHART vs conventional radiotherapy in head and neck and non-small cell lung cancer: an interim report. Br J Cancer 1996;73:1455–62.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Jeremic B, Shibamoto Y, Acimovic L, et al. Randomized trial of hyperfractionated radiation therapy with or without concurrent chemotherapy for stage III non small cell lung cancer. J Clin Oncol 1995;13:452–8.PubMedGoogle Scholar
  15. 15.
    Jeremic B, Shibamoto Y, Acimovic L, et al. Hyperfractionated radiation therapy with or without, concurrent lowdose daily carboplatin/etoposide for stage III non-small cell lung cancer. J Clin Oncol 1996;14:1065–70.PubMedGoogle Scholar
  16. 16.
    Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomized clinical trials. BMJ 1995;311:899–909.CrossRefGoogle Scholar
  17. 17.
    Sörenson S, Glimelius B, Nygren P. A systematic overview of chemotherapy effects in non-small cell lung cancer. Acta Oncol 2001;40:327–39.CrossRefPubMedGoogle Scholar
  18. 18.
    Curran WJ, Scott C, Langer R, et al. Phase III comparison of sequential vs concurrent chemoradiation for pts with unresected stage III non-small cell lung cancer: initial report of Radiation Therapy Oncology Group 9410. Proc Am Soc Clin Oncol 2000;19:1891.Google Scholar
  19. 19.
    Furuse K, Hosoe S, Masuda N, et al. Impact of tumor control on survival in unresectable stage III non-small cell lung cancer treated with concurrent throacic radiotherapy and chemotherapy. Proc Am Soc Clin Oncol 2000: 19:1893.Google Scholar
  20. 20.
    Stevens CW, Lee JS, Cox J, et al. Novel approaches to locally advanced unresectable non-small cell lung cancer. Radiother Oncol 2000;55:11–8.CrossRefPubMedGoogle Scholar

Copyright information

© FESEO 2002

Authors and Affiliations

  • Martín Tejedor Gutiérrez
    • 1
    Email author
  • Juan José Valerdi Álvarez
    • 1
  • Begoña Bermejo Fraile
    • 1
  • Juan Ignacio Arraras Urdaniz
    • 1
  • Ruth Vera García
    • 1
  • Francisco Molina Rosillo
    • 1
  • Juan José Albistur Tomé
    • 1
  1. 1.Servicio de Oncología RadioterápicaHospital TxagorritxuVitoria-Gasteiz

Personalised recommendations