Combined modality treatment using concurrent radiotherapy and pharmacologically-guided carboplatin for inoperable and incompletely resected non-small cell lung cancer

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. Patients and 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 <greater than or equal to> grade 3 occurred in 14 patients (29%) tone patient died of pneumonia while neutropenic); two patients developed greater than or equal to grade 3 acute oesophagitis and two patients had greater than or equal to grade 3 acute pulmonary toxicity. Late pulmonary toxicity greater than or equal to 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). (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.