High frequency of radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent radiotherapy and gemcitabine after induction with gemcitabine and carboplatin.
BACKGROUND
The combination of chemotherapy and thoracic radiation is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). However, most favorable chemotherapy regimen, timing of full-dose chemotherapy, and optimal combination of chemotherapy with radiation remain to be determined. Our primary objective was to evaluate the efficacy and safety of gemcitabine concurrent with radiotherapy after induction chemotherapy with gemcitabine plus carboplatin for locally advanced NSCLC.


METHODS
Patients with histologically proven NSCLC stage IIIA and -B received carboplatin (area under the curve of 2.5) and gemcitabine (800 mg/m) on days 1 and 8, every 21 days for two cycles, followed by conventional fractioned thoracic radiotherapy and concomitant weekly gemcitabine 200 mg/m, and finally, consolidation chemotherapy.


RESULTS
Inclusion was discontinued because of high-grade 3 to 5 radiation-pneumonitis events (6 of 19 patients, 31.6%), including one treatment-related death associated with radiation pneumonitis. Median follow-up was 11.9 months. Most common grades 3/4 hematological side effects comprised anemia, neutropenia 3 of 19 patients, each (15.8%), and thrombocytopenia (4 of 19, 21.1%) during induction. Partial response was observed in 10 patients (52.6%) following induction chemotherapy. After concurrent chemo-radiotherapy, overall response was 68.4%. Four patients (21.1%) underwent surgical resection. Median progression-free survival and overall survival were 12 +/- 1 month (95% confidence interval [CI], 9.8-14.1) and 21 +/- 3.5 months (95% CI, 14-27.9 months), respectively.


CONCLUSIONS
Concurrent radiotherapy with gemcitabine after induction with gemcitabine and carboplatin showed a high-response rate; however, it is associated with excessive pulmonary toxicity. Adjustments in gemcitabine dosage during radiotherapy or changes in radiotherapy planning could reduce toxicity.
Arrieta
Oscar
O
Department of Medical Oncology, Experimental Oncology Laboratory, Instituto Nacional de Cancerología, Mexico City, Mexico. ogar@servidor.unam.mx
Gallardo-Rincón
Dolores
D
Villarreal-Garza
Cynthia
C
Michel
Rosa M
RM
Astorga-Ramos
Alma M
AM
Martínez-Barrera
Luis
L
de la Garza
Jaime
J
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D009367:Neoplasm Staging; D017564:Radiation Pneumonitis / Q000453:epidemiology*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects; D011879:Radiotherapy Dosage; D015996:Survival Rate; D000093542:Gemcitabine
D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D016190:Carboplatin; D000093542:Gemcitabine