[Dose-response effect of drugs in the chemotherapy of small-cell bronchial carcinoma].
Dose-intensity is an amount of drug delivered per unit of time, expressed as mg/m2/week, regardless of the schedule or route of administration. Relative dose intensity is an amount of drug delivered per unit of time relative to an arbitrary chosen standard single drug or, in a combination regimen, the decimal fraction of the ratio of the average dose-intensity of all drugs of the test regimen compared to the standard regimen. Calculations can be made with intended (planned) dose intensity or actual or received dose intensity. A positive effect of dose intensity on outcome (response rate) has been demonstrated in advanced ovarian, colon, breast cancers and lymphomas. Small-cell lung cancer (SCLC) is very responsive to chemotherapy, although in the majority of patients conventional-dose chemotherapy is not effective in meaningfully prolonging median survival. Randomized studies suggest that a dose may be important for the success of chemotherapy in SCLC. The aim of the present study was to investigate the relation between dose-intensity and tumour objective response in a group of patients with SCLC treated with two cysplatin-based regimens. Fifty patients were randomized to receive 60 mg/m2 of a cysplatin and 120 mg/m2 of etoposide on days 1, 3 and 5 (Group A), or the same dose of cysplatin and 120 mg/m2 of epirubicin (Group B). The intercylce interval was 4 weeks, and 6 cycles were planned. The planned dose-intensity of cysplatin was calculated as 15 mg/m2/wk. However, the actual or received dose-intensity of cysplatin was 12.55 +/- 1.7 mg/m2/wk and 13.62 +/- 3.1 mg/m2/wk in Group A and Group B of patients, respectively. In other words, in the combination with etoposide, 83.7% of the planned dose of cysplatin has been delivered, while in the combination with epirubicin the cysplatin dose-intensity was 90.8%. The received dose-intensity of etoposide was calculated as 77.7% (planned dose intensity was 90 mg/m2/wk and actual dose-intensity 70 mg/m2/wk). Similarly, the received dose intensity of epirubicin was found to be 82.3% (30 mg/m2/wk planned and 24.4 mg/m2/wk actual). The average dose intensity in Group A was found to be 80.72% and in Group B 86.04%. Compared to patients with stable and progressive disease, the patients obtained objective tumour response received 5% and 10% higher relative dose intensity of cysplatin in Group A and Group B, respectively. Relative dose intensity of etoposide and epirubicin were similar in patients with or without objective tumour response. In conclusion, a positive relation between cysplatin dose intensity and objective tumour response was demonstrated. A higher relative dose intensity of cysplatin could be reached in combination with epirubicin compared to combination with etoposide.
Knez Selo Lung Diseases and Tuberculosis Hospital, Nish.
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D
Kostić
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Jelić
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Radulović
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged
D015251:Epirubicin; D005047:Etoposide; D002945:Cisplatin