title: Combined modality treatment using concurrent radiotherapy and pharmacologically-guided carboplatin for inoperable and incompletely resected non-small cell lung cancer.
abstract: BACKGROUND
  In our previous randomised trial, radiotherapy (RT) was given concurrently with carboplatin 350 mg/m(2). We wanted to show that the safety and efficacy of the drug could be improved by pharmacologically-guided dosing based on renal function.
  
  
  METHODS
  Patients were eligible if they had unresectable or incompletely resected NSCLC, good performance status (ECOG 0-2), weight loss < 10%, no distant metastases and adequate haematology and biochemistry. Radiotherapy was given to the primary site and regional lymph nodes to a total dose of 60 Gy in 30 fractions over 6 weeks. Two cycles of carboplatin were given in divided doses of 1-h infusions daily for 5 days before RT weeks 1 and 6. A total plasma AUC of 7 mg/ml per minute per cycle was targeted. The total dose was calculated by using Calvert or Chatelut formulae.
  
  
  RESULTS
  Forty-nine patients were treated. Patient characteristics included: 78% male; mean age 66 (range: 38--78); 80% stage 3A or 3B; incomplete resection in six patients. The median dose of carboplatin administered per cycle was 850 mg (range 435--1650); 89% of patients received a higher carboplatin dose compared with BSA-calculated dose (mean increase 41%). Forty-two patients (86%) completed treatment as planned. Myelosuppression > or = grade 3 occurred in 14 patients (29%) (one patient died of pneumonia while neutropenic); two patients developed > or = grade 3 acute oesophagitis and two patients had > or = grade 3 acute pulmonary toxicity. Late pulmonary toxicity > or = grade 3 occurred in two patients. The mean potential follow-up time was 2.7 years. The estimated proportion of patients alive and free of local or distant progression at 1 year was 42% and the median survival duration was 16 months (95% CI: 11--21 months).
  
  
  CONCLUSIONS
  Radical chest irradiation can be combined with two cycles of pharmacologically-guided full-dose carboplatin, however because our study demonstrated significant haematologic toxicity, we recommend carboplatin dosing according to renal function at less than full dose (i.e. AUC 6 mg/ml per minute per cycle).
authors.affiliation: Division of Radiation, Peter MacCallum Cancer Institute, Locked Bag No 1, A'Beckett Street, East Melbourne, Victoria 3002, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Grossi
authors.forename: M
authors.initials: M
authors.lastname: Millward
authors.forename: R
authors.initials: R
authors.lastname: Fisher
authors.forename: S
authors.initials: S
authors.lastname: Porceddu
authors.forename: M
authors.initials: M
authors.lastname: Mac Manus
authors.forename: G
authors.initials: G
authors.lastname: Ryan
authors.forename: A
authors.initials: A
authors.lastname: Wirth
authors.forename: D
authors.initials: D
authors.lastname: Ball
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin