title: 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.
abstract: 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.
authors.affiliation: Department of Medical Oncology, Experimental Oncology Laboratory, Instituto Nacional de Cancerología, Mexico City, Mexico. ogar@servidor.unam.mx
authors.forename: Oscar
authors.initials: O
authors.lastname: Arrieta
authors.forename: Dolores
authors.initials: D
authors.lastname: Gallardo-Rincón
authors.forename: Cynthia
authors.initials: C
authors.lastname: Villarreal-Garza
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Michel
authors.forename: Alma M
authors.initials: AM
authors.lastname: Astorga-Ramos
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Barrera
authors.forename: Jaime
authors.initials: J
authors.lastname: de la Garza
mesh_terms: 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
chemical_list: D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D016190:Carboplatin; D000093542:Gemcitabine