Docetaxel: Emerging Options in the Management of Non-Small-Cell Lung Cancer

In the United States, an estimated 178,000 new cases of lung cancerwill occur in 1997, accounting for 13% of cancer diagnoses and 29% of allcancer deaths.[1] The majority of these deaths will be due to metastaticnon-small-cell lung cancer. Cisplatin (Platinol), vindesine (Eldisine),vinblastine, ifosfamide (Ifex), and mitomycin (Mutamycin) demonstrate responserates of 15% or higher in previously untreated patients (Table1).[2] All of these drugs were identified in the 1970s and 1980s. Noneshowed reproducible response rates greater than 25% when given as singleagents.

Combining these drugs can improve response rates to 25% to 45% in chemotherapy-naivepatients with advanced non-small-cell lung cancer.[3] Using these cisplatin-basedcombination regimens, median survival doubled compared to that of similarpatients receiving only supportive care.[4]

When first-line, single-agent chemotherapy fails, retreatment with thesame agent is unlikely to be successful. Combination regimens are generallypreferred. However, response rates in this situation have been disappointing,generally not exceeding 10%, with median survival less than 6 months.[5]

Since 1990, several important new drugs in the treatment of non-small-celllung cancer have emerged (Table 1). Thissupplement reviews the latest data on docetaxel (Taxotere) for use in patientswith advanced non-small-cell lung cancer. Frank V. Fossella, MD, addressesthe use of docetaxel in patients with advanced non-small-cell lung cancerand disease progression following treatment with cisplatin or carboplatin.Data from four phase II studies suggest that 100 mg/m² of docetaxel,administered over 1 hour, once every 3 weeks, provides benefits that aregreater than those seen so far with other newer agents in this setting.Major responses with other newer agents have been in the range of 0% to10%. For docetaxel, response rates have ranged from 14% to 22%, and themedian survival from 7 to 10 months.

The second article, by James R. Rigas, MD, discusses data from a numberof phase II trials that show the efficacy of single-agent docetaxel inpreviously untreated patients with non-small-cell lung cancer. In thissetting, 100 mg/m² of docetaxel administered over 1 hour, once every3 weeks, produces major response rates in 27% of patients and a mediansurvival of 9 months, with a 1-year survival rate of 34%.

The use of docetaxel with concomitant chest radiotherapy in patientswith Stage IIIA and IIIB non-small-cell lung cancer is presented by EverettE. Vokes, MD, and colleagues. This article discusses preliminary data froman ongoing phase I trial designed to determine the maximum tolerated andoptimal doses of docetaxel when administered with chest radiotherapy.

Combinations of docetaxel with cisplatin (Platinol), carboplatin (Paraplatin),and vinorelbine (Navelbine) are the topics of the next three articles.Richard J. Gralla, MD, offers preliminary results of ongoing phase I-IIstudies showing that the combination of docetaxel, 75 mg/m², and cisplatin,75 mg/m², (or docetaxel, 65 mg/m², and cisplatin, 100 mg/m²)in previously untreated patients with non-small-cell lung cancer producesfavorable response rates, with median survival of 9 to 11 months.

In the next article, Chandra P. Belani, MD, provides an update on theprogress made with trials of docetaxel and carboplatin. The concludingfeature by Jeffrey Crawford, MD, discusses the results of recent phaseI and II trials of the promising combination of two newer chemotherapeuticagents, docetaxel and vinorelbine. This article describes three phase IItrials investigating 75 or 100 mg/m² of docetaxel, followed by 20or 22 mg/m² of vinorelbine, both administered by intravenous infusionover 1 hour, once every 3 weeks, which yielded response rates ranging from23% to 55%.

References:

1. Parker SL, Tong T, Bolden S, et al: Cancer statistics, 1997. CA CancerJ Clin 47:5-27, 1997.

2. Ginsberg JG, Kris MG, Armstrong JG: Cancer of the lung: Non-smallcell lung cancer, in De Vita VT, Hellman S, Rosenberg SA (eds): Cancer:Principles & Practice of Oncology, 4th ed, pp 673-758. Philadelphia,JB Lippincott Co., 1993.

3. Crino L, Clerici M, Figoli F, et al: Chemotherapy of advanced non-small-celllung cancer: A comparison of three active regimens: A randomized trialof the Italian Oncology Group for Clinical Research (G.O.I.R.C.). Ann Oncol6:347-353, 1995.

4. Non-Small Cell Lung Cancer Collaborative Group: Chemotherapy in non-smallcell lung cancer: A meta-analysis using updated data on individual patientsfrom 52 randomized clinical trials. Br Med J 311:899-909, 1995.

5. Miller VA, Rigas JR, Pisters KM, et al: Ifosfamide plus high-dosecisplatin in patients with non-small cell lung cancer previously treatedwith chemotherapy. Am J Clin Oncol 18:303-306, 1995.