Journal Information
Vol. 43. Issue 7.
Pages 358-365 (January 2007)
Share
Share
Download PDF
More article options
Vol. 43. Issue 7.
Pages 358-365 (January 2007)
Original Articles
Full text access
Stage IIIA and IIIB Non-Small Cell Lung Cancer: Results of Chemotherapy Combined With Radiation Therapy and Analysis of Prognostic Factors
Visits
5288
Julio Sánchez de Cos Escuína,
Corresponding author
jsd01cc@saludalia.com

Correspondence: Dr. J. Sánchez de Cos Escuín. Isla de Hierro, 2, 3. ° C. 10001 Cáceres. España
, Isabel Utrabo Delgadoa, Joaquín Cabrera Rodríguezb, Marcelo Jiménez Lópezc, Carlos Disdier Vicentea, J. Antonio Riesco Mirandaa
a Sección de Neumología, Hospital San Pedro de Alcántara, Cáceres, Spain
b Servicio de Radioterapia, Clínica San Francisco, Cáceres, Spain
c Servicio de Cirugía Torácica, Hospital Clínico Universitario, Salamanca, Spain
This item has received
Article information
Abstract
Bibliography
Download PDF
Statistics
OBJECTIVE

Most patients with stage III non-small cell lung cancer (NSCLC) are not candidates for surgery but can benefit from chemotherapy combined with radiation therapy. The objective of the present study was to analyze the results of sequential chemotherapy and radiation therapy and the prognostic value of initial clinical and laboratory variables.

PATIENTS AND METHODS

We carried out a retrospective study of 92 patients with stage III NSCLC treated with a sequential regimen of chemotherapy (carboplatin–etoposide, carboplatin–gemcitabine, and carboplatin–paclitaxel), and radiation therapy (6000 cGy in daily doses of 200 cGy, 5 d/wk). Response to therapy, overall survival, and the prognostic value of epidemiological, clinical, and laboratory variables were evaluated using univariate and multivariate analyses.

RESULTS

Median survival time was 14 months, with a 3-year survival rate of 16.1%. Poor performance status (score of 2 on the Eastern Cooperative Oncologic Group [ECOG] scale), anemia, and elevated serum concentrations of carcinoembryonic antigen were predictive of poorer survival in the multivariate analysis. In the univariate analysis, weight loss and diagnosis before the year 2000 were also associated with poorer prognosis (P <.01). TNM stage was not significantly correlated (P=.08). Toxicity was low, with 1 death and few cases of grade 3 or 4 toxicity according to World Health Organization criteria.

CONCLUSIONS

The use of chemotherapy combined with radiation therapy should be considered contraindicated in cases of poor performance status (ECOG scale score of 2). Weight loss, an elevated serum concentration of carcinoembryonic antigen, and a hemoglobin concentration of less than 12 g/dL carry a poor prognosis.

Key words:
Non-small cell lung cancer
Stage III
Chemotherapy
Radiation therapy
Prognostic factors
OBJETIVO

La mayoría de los pacientes con carcinoma de pulmón no microcítico y estadio III no son candidatos a cirugía y pueden beneficiarse del tratamiento combinado con quimioterapia (QT) y radioterapia (RT). En este trabajo se han analizado los resultados de una pauta combinada secuencial y el valor pronóstico de variables clínicas y analíticas iniciales.

PACIENTES Y MÉTODOS

Se ha realizado un estudio retrospectivo de 92 pacientes con carcinoma de pulmón no microcítico y estadio III tratados con una pauta secuencial combinada de QT (3 combinaciones diferentes de carboplatino: con etopósido, con gencitabina y con paclitaxel) y RT (6.000 cGy: 200 cGy diarios, 5 días/semana). Se evaluaron la respuesta, la supervivencia global y el valor pronóstico de variables epidemiológicas, clínicas y analíticas mediante análisis univariante y multivariante.

RESULTADOS

La supervivencia mediana fue de 14 meses, con una supervivencia a los 3 años del 16,1%. El mal estado general–grado 2 de la escala del Eastern Cooperative Oncological Group (ECOG)–, la anemia y las concentraciones séricas elevadas de antígeno carcinoembrionario fueron predictivos de peor supervivencia en el modelo multivariante. Además, en el análisis univariante la pérdida de peso y los diagnosticados antes del año 2000 también se asociaron a peor pronóstico (p < 0,01). El grado TNM no alcanzó la significación estadística (p = 0,08). La toxicidad fue escasa; hubo una muerte y pocos casos de grados III y IV de la Organización Mundial de la Salud.

CONCLUSIONES

Un mal estado general (ECOG 2) debe considerarse una contraindicación para el uso de pautas combinadas de QT y RT. La pérdida de peso, las concentraciones séricas elevadas de antígeno carcinoembrionario y una cifra de hemoglobina igual o inferior a 12 g/dl conllevan peor pronóstico.

Palabras clave:
Carcinoma de pulmón no microcítico
Estadio III
Quimioterapia
Radioterapia
Factores pronósticos
Full text is only aviable in PDF
REFERENCES
[1]
J van Meerbeeck, G Kramer, PE van Schil, C Legrand, EF Smit, FM Schramel, et al.
EORTC-Lung Cancer Group. A randomized trial of radical surgery (RS) versus thoracic radiotherapy (TRT) in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) after response to induction chemotherapy (ICT) (EORTC 08941).
J Clin Oncol, 23 (2005), pp. 7015
[2]
KS Albain, RS Swann, VR Rusch, AT Turrisi, FA Shepherd, CJ Smith, et al.
North American Lung Cancer Intergroup. Phase III study of concurrent chemotherapy and radiotherapy (CT/RT) vs CT/RT followed by surgical resection for stage IIIA (pN2) non-small cell lung cancer (NSCLC): outcomes update of North American Intergroup 0139 (RTOG 9309).
J Clin Oncol, 23 (2005), pp. 7014
[3]
RO Dillman, SL Seagren, KJ Propert, J Guerra, WL Eaton, MC Perry, et al.
A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small cell lung cancer.
N Engl J Med, 323 (1990), pp. 940-945
[4]
T le Chevalier, R Arriagada, E Quoix, P Ruffie, M Martin, M Tarayre, 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, 83 (1991), pp. 417-423
[5]
W Sause, P Kolesar, S Taylor, D Johnson, R Livingston, R Komaki, et al.
Final results of phase III trial in regionally advanced unresectable non small cell lung cancer.
Chest, 117 (2000), pp. 358-364
[6]
MH Cullen, LJ Billingham, AD Woodroffe, AD Chetiyarawardana, NH Gower, R Joshi, et al.
Mitomycin, ifosfamide and cisplatin in unresectable non-small cell lung cancer: effects on survival and quality of life.
J Clin Oncol, 17 (1999), pp. 3188-3194
[7]
K Furuse, M Fukuoka, M Kawahara, H Nishikawa, Y Takada, S Kudoh, et al.
Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine and cisplatin in unresectable stage III non small cell lung cancer.
J Clin Oncol, 17 (1999), pp. 2692-2699
[8]
H West, KS Albain.
Current standards and ongoing controversies in the management of locally advanced non small cell lung cancer.
Semin Oncol, 32 (2005), pp. 284-292
[9]
International Commission on Radiations Units and Measurements.
Prescribing, recording and reporting photon beam therapy. ICRU Report 50, ICRU, (1993),
[10]
MV Graham, JA Purdy, B Emmami, W Harms, W Bosch, MA Lockett, et al.
Clinical DVH analysis for pneumonitis after 3D treatment NSCLC.
Int J Radiat Oncol Biol Phys, 45 (1999), pp. 323-329
[11]
JA Hayman, MK Martel, RK ten Haken, PD Normolle, RF Todd III, JF Littles, et al.
Dose escalation in non-small-cell lung cancer using three-dimensional conformal radiation therapy: update of a phase I trial.
J Clin Oncol, 19 (2001), pp. 127-136
[12]
KE Rosenzweig, SE Sim, B Mychalczak, LE Braban, R Schindelheim, SA Leibel.
Elective nodal irradiation in the treatment of non-small-cell lung cancer with three-dimensional conformal radiation therapy.
Int J Radiat Oncol Biol Phys, 50 (2001), pp. 681-685
[13]
S Senan, JA Burgers, MJ Samson, J van Klaveren, SS Osei, J van Sornsen de Koste, et al.
Can elective nodal irradiation be omitted in stage III non-small cell lung cancer? An analysis of recurrences in a phase II study of induction chemotherapy and “involved-field” radiotherapy.
Int J Radiat Oncol Biol Phys, 54 (2002), pp. 999-1006
[14]
B Emami, N Mirkovic, C Scott, R Byhardt, MV Graham, E James Andras, et al.
Impact of regional nodal radiotherapy (dose/volume) on regional progression and survival in unresectable non-small cell lung cancer: an analysis of RTOG data.
Lung Cancer, 41 (2003), pp. 207-214
[15]
P Therasse, SG Arbuck, EA Eisenhauer, J Wanders, RS Kaplan, L Rubinstein, et al.
New guidelines to evaluate the response to treatment in solid tumors.
J Natl Cancer Inst, 92 (2000), pp. 205
[16]
AB Miller, B Hoogstraten, M Staquet, A Winkler.
Reporting the results of cancer treatment.
Cancer, 47 (1981), pp. 207-214
[17]
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 randomised trials.
BMJ, 311 (1995), pp. 899-909
[18]
M Saunders, S Dische, A Barrett, A Harvey, D Gibson, M Parmar, et al.
Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non small cell lung cancer: a randomised trial.
Lancet, 350 (1997), pp. 161-165
[19]
PD Maguire, LB Marks, GS Sibley, JE Herndon, RW Clough, KL Light, et al.
73.6 Gy and beyond: hyperfractionated, accelerated radiotherapy for non small cell lung cancer.
J Clin Oncol, 19 (2001), pp. 705-711
[20]
D Lau, B Leigh, D Gándara, M Edelman, R Morgan, V Israel, et al.
Twice-weekly paclitaxel and weekly carboplatin with concurrent thoracic radiation followed by carboplatin/paclitaxel consolidation for stage III non small cell lung cancer: a California cancer consortium phase II trial.
J Clin Oncol, 19 (2001), pp. 442-447
[21]
MA Socinski, JG Rosenman, J Halle, MJ Schell, Y Lin, S Russo, et al.
Dose-escalating conformal thoracic radiation therapy with induction and concurrent carboplatin/paclitaxel in unresectable stage IIIA/B non small cell carcinoma.
Cancer, 92 (2001), pp. 1213-1223
[22]
B Jeremic, B Milicic, L Acimovic, S Miliasavljevic.
Concurrent hyperfractionated radiotherapy and low-dose daily carboplatin and paclitaxel in patients with stage III non small cell lung cancer: long-term results of a phase II study.
J Clin Oncol, 23 (2005), pp. 1144-1151
[23]
CP Belani, H Choy, P Bonomi, C Scott, P Travis, J Haluschak, et al.
Combined chemotherapy regimens of paclitaxel and carboplatin for locally advanced non small cell lung cancer: a randomized phase II locally advanced multi-modality protocol.
J Clin Oncol, 23 (2005), pp. 5883-5891
[24]
JJ Olasolo, E Alonso Redondo, A León Jiménez, A Rueda Ramos.
Carcinoma no microcítico de pulmón. Supervivencia y factores pronósticos del tratamiento radioterápico.
Arch Bronconeumol, 39 (2003), pp. 81-86
[25]
LJ Schouten, J Rutten, HAM Huveneers, A Twijnstra.
Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney and lung and melanoma.
Cancer, 94 (2002), pp. 2698-2705
[26]
HJ Mamon, BY Yeap, PA Jänne, J Reblando, S Shrager, MT Jaklitsch, et al.
High risk of brain metastases in surgically staged IIIA non small cell lung cancer patients treated with surgery, chemotherapy and radiation.
J Clin Oncol, 23 (2005), pp. 1530-1537
[27]
SE Schild, PJ Stella, SM Geyer, JA Bonner, RS Marks, WL McGinnis, et al.
A phase III trial comparing chemotherapy plus either once a day radiotherapy or twice a day radiotherapy in stage III non small cell lung cancer.
Int J Radiat Oncol Biol Phys, 54 (2002), pp. 370-378
[28]
SE Schild, PJ Stella, SM Geyer, JA Bonner, McGinnis WL, JA Mailliard, et al.
The outcome of combined-modality therapy for stage III non small cell lung cancer in the elderly.
J Clin Oncol, 21 (2003), pp. 3201-3206
[29]
MA Socinski, C Zhang, JE Herndon, RO Dillman, G Clamon, E Vokes.
Combined modality trials of the cancer and leukemia group B in stage III non small cell lung cancer: analysis of factors influencing survival and toxicity.
Ann Oncol, 15 (2004), pp. 1033-1041
[30]
DH Lau, JJ Crowley, DR Gándara, MB Hazuka, KS Albain, B Leigh, et al.
Southwest Oncology Group phase II trial of concurrent carboplatin, etoposide, and radiation for poor-risk stage III non small cell lung cancer.
J Clin Oncol, 16 (1998), pp. 3078-3081
[31]
J Sánchez de Cos.
Utilidad clínica de los marcadores tumorales en el cáncer de pulmón [dissertation], Universidad de Extremadura, (1992),
[32]
T Yoshimasu, S Miyoshi, S Maebeya, T Suzuma, T Besso, I Hirai, et al.
Analysis of the early postoperative serum carcinoembryonic antigen time-course as a prognostic tool for bronchogenic carcinoma.
Cancer, 79 (1997), pp. 1533-1540
[33]
B Milleron, V Westeel, E Quoix, D Moro-Sibilot, D Braun, B Lebeau, et al.
Complete response following preoperative chemotherapy for resectable non small cell lung cancer.
Chest, 128 (2005), pp. 1442-1447
[34]
SE Schild, JA Bogart.
Innovations in the radiotherapy of non small cell lung cancer.
J Thorac Oncol, 1 (2006), pp. 85-92
Copyright © 2007. Sociedad Española de Neumología y Cirugía Torácica (SEPAR)
Archivos de Bronconeumología
Article options
Tools

Are you a health professional able to prescribe or dispense drugs?