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

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

In the United States, an estimated 178,000 new cases of lung cancer will occur in 1997, accounting for 13% of cancer diagnoses and 29% of all cancer deaths.[1] The majority of these deaths will be due to metastatic non-small-cell lung cancer. Cisplatin (Platinol), vindesine (Eldisine), vinblastine, ifosfamide (Ifex), and mitomycin (Mutamycin) demonstrate response rates of 15% or higher in previously untreated patients (Table 1).[2] All of these drugs were identified in the 1970s and 1980s. None showed reproducible response rates greater than 25% when given as single agents.

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

When first-line, single-agent chemotherapy fails, retreatment with the same agent is unlikely to be successful. Combination regimens are generally preferred. 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-cell lung cancer have emerged (Table 1). This supplement reviews the latest data on docetaxel (Taxotere) for use in patients with advanced non-small-cell lung cancer. Frank V. Fossella, MD, addresses the use of docetaxel in patients with advanced non-small-cell lung cancer and 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 are greater 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% to 10%. For docetaxel, response rates have ranged from 14% to 22%, and the median survival from 7 to 10 months.

The second article, by James R. Rigas, MD, discusses data from a number of phase II trials that show the efficacy of single-agent docetaxel in previously untreated patients with non-small-cell lung cancer. In this setting, 100 mg/m² of docetaxel administered over 1 hour, once every 3 weeks, produces major response rates in 27% of patients and a median survival of 9 months, with a 1-year survival rate of 34%.

The use of docetaxel with concomitant chest radiotherapy in patients with Stage IIIA and IIIB non-small-cell lung cancer is presented by Everett E. Vokes, MD, and colleagues. This article discusses preliminary data from an ongoing phase I trial designed to determine the maximum tolerated and optimal 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-II studies 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 produces favorable response rates, with median survival of 9 to 11 months.

In the next article, Chandra P. Belani, MD, provides an update on the progress made with trials of docetaxel and carboplatin. The concluding feature by Jeffrey Crawford, MD, discusses the results of recent phase I and II trials of the promising combination of two newer chemotherapeutic agents, docetaxel and vinorelbine. This article describes three phase II trials investigating 75 or 100 mg/m² of docetaxel, followed by 20 or 22 mg/m² of vinorelbine, both administered by intravenous infusion over 1 hour, once every 3 weeks, which yielded response rates ranging from 23% to 55%.

References

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

2. Ginsberg JG, Kris MG, Armstrong JG: Cancer of the lung: Non-small cell 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-cell lung cancer: A comparison of three active regimens: A randomized trial of the Italian Oncology Group for Clinical Research (G.O.I.R.C.). Ann Oncol 6:347-353, 1995.

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

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

 
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