Combination studies with gemcitabine in the treatment of non-small-cell lung cancer.
Phase II studies have confirmed gemcitabine (GEMZAR) to be an active single agent in treating non-small-cell lung cancer (NSCLC), with response rates averaging 21%. Toxicity, including myelosuppression, is mild, making gemcitabine an attractive agent to consider in combination regimens. Most experience with gemcitabine in combination has been with cisplatin. Five phase II studies have been performed using different scheduling and dosage regimens. Response rates varied from 38% to 54% and median survival was 8.4-14.3 months. This combination was well tolerated and required minimal hospitalization. Haematological toxicity of short duration was dose limiting, with thrombocytopenia WHO grades 3/4 in 16-52% of patients and neutropenia in 36-58%. Nausea and vomiting occurred with cisplatin. Ifosfamide has been combined with gemcitabine in a phase I/II study. Based on phase I data, ifosfamide 1500 mg m(-2)day(-1) was chosen for the phase II study. The overall response rate was 32%. Toxicity was mild and was mainly related to short-lived myelosuppression. In summary, the favourable toxicity profile of single-agent gemcitabine enables its safe combination with other active agents in the treatment of NSCLC. The combination with cisplatin appears particularly encouraging, and a phase III study comparing this combination with standard chemotherapy regimens is planned. The combination of gemcitabine with radiotherapy is also under investigation.
Steward
W P
WP
University Department of Oncology, Leicester Royal Infirmary, UK.
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D008875:Middle Aged; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
D003841:Deoxycytidine; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine; D007069:Ifosfamide; D000093542:Gemcitabine