Management of Advanced Non-Small Cell Lung Cancer: The Potential Role of Gemcitabine

Patients with non-small cell lung cancer (NSCLC) have poor survival prospects, as most have advanced disease at diagnosis. Chemotherapy can be used to treat these patients if their performance status is good, although there are geographical differences in chemotherapy use. Combination chemotherapy regimens are usually used because monochemotherapy has only modest efficacy. The nucleoside analogue gemcitabine is one of several new chemotherapies for NSCLC which have been developed in recent years. Like other available drugs, it has modest efficacy against NSCLC when used as monotherapy [19 to 26% objective (partial plus complete) response rate]. Gemcitabine is relatively well tolerated, causing few serious adverse effects. Myelosuppression is the most common reason for dosage adjustment during monotherapy, but such adjustments are relatively infrequent overall. Flu-like symptoms and fever, elevated hepatic enzyme levels, and nausea and vomiting are common but are usually mild or moderate. Dosage reduction and treatment withdrawal are the exception rather than the rule for patients receiving gemcitabine monotherapy. The combination of gemcitabine with cisplatin has shown good antitumour efficacy (26 to 54% objective response rate) in patients with NSCLC, and limited phase III data suggest that it produces objective response rates significantly higher than those of some older `standard' regimens such as cisplatin plus etoposide (although survival appears similar). Gemcitabine plus cisplatin produces grade 3 or 4 myelosuppression in many patients, but this has generally proved manageable and has not limited clinical use. Data from phase III comparisons of gemcitabine plus cisplatin with currently recommended combination regimens (which include some of the other newer agents for NSCLC, e.g. paclitaxel or vinorelbine) are not yet available. Conclusions. Gemcitabine is now a well established chemotherapy for NSCLC which is approved for use in many countries, but its precise role in an indication with numerous treatment options and combination regimens is clearly still evolving. Gemcitabine-containing combination regimens are being tested in a number of phase III trials and data from these studies are awaited with interest. The relatively benign tolerability profile of gemcitabine may prove useful in elderly patients (limited available data from this group are favourable) or patients with coexisting disease states, since tolerance of toxicities is likely to be lower in these groups than in other patients. Non-cisplatin-based combination regimens are currently being investigated in an attempt to further improve the tolerability of chemotherapy for NSCLC, and gemcitabine is likely to play a significant role in this respect.