Challenging the platinum combinations in the chemotherapy of NSCLC.
In previously untreated patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) the combination of docetaxel and gemcitabine is active and well tolerated. In the phase II setting using a 3-week schedule, response rates (RR) ranged from 25 to 50%, and median survival from 11 to 13 months. Preliminary data with weekly and bi-weekly schedules indicate maintained efficacy while reducing the risk of neutropenia. A randomized phase III trial has shown that the combination of docetaxel and gemcitabine is as active as docetaxel plus cisplatin, achieving a 1-year survival rate of 39%, with significantly less neutropenia and gastro-intestinal toxicity. The combination of docetaxel with vinorelbine is equally active and the associated toxicities are manageable. In phase II studies the average response rate is 40%, and in one study using a 2-week schedule the 1-year survival rate was 60%. With this combination neutropenia is the commonest adverse event while clinically significant neuropathy is infrequent. In a randomized phase II trial, docetaxel plus cisplatin was compared to docetaxel plus irinotecan. The non-platinum doublet achieved comparable levels of activity, though with a different toxicity profile (more diarrhea but less nausea and vomiting). The combination of docetaxel with irinotecan and carboplatin has achieved 1-year survival of 55%. All three docetaxel combinations (gemcitabine, vinorelbine, and irinotecan) could provide a valuable alternative to platinum-based chemotherapy and should be further evaluated in phase III setting.
Douillard
J-Y
JY
Centre R Gauducheau, St-Herblain, France.
Eckardt
J
J
Scagliotti
G V
GV
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077143:Docetaxel; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D043823:Taxoids; D000093542:Gemcitabine
D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000077146:Irinotecan; D017239:Paclitaxel; D002945:Cisplatin; D002166:Camptothecin; D000093542:Gemcitabine