Paclitaxel, carboplatin, and extended schedule etoposide in the treatment of small cell lung carcinoma.

BACKGROUND

Paclitaxel is an active agent in the initial treatment of patients with small cell lung carcinoma. The authors evaluated the toxicity and efficacy of paclitaxel (1-hour infusion) added to a standard combination regimen of carboplatin and etoposide in a Phase II trial for the treatment of patients with small cell lung carcinoma.

METHODS

Thirty-eight patients with previously untreated small cell lung carcinoma were treated with a combination regimen including paclitaxel, 135 mg/m2 by 1-hour intravenous (i.v.) infusion, on Day 1; carboplatin at AUC 5, on Day 1; and oral etoposide, 100 mg alternated with 50 mg, on days 1-10. Prior to availability of reimbursement for oral etoposide, 13 patients received etoposide, 25 mg/m2 i.v. on Days 1-5 and 8-12. Treatment courses were repeated every 21 days for a total of 4 courses. Patients with limited stage disease received radiation therapy (4500 centrigray in 25 fractions) concurrently with the last 2 courses of chemotherapy.

RESULTS

This combination chemotherapy regimen was easily tolerated. Eleven episodes of Grade 3 or 4 leukopenia occurred in 9 patients (8% of courses); Grade 3 and 4 thrombocytopenia and anemia were also infrequent. Fifteen patients were hospitalized for treatment of fever associated with leukopenia. Concurrent treatment with chemotherapy and radiation therapy was also tolerable, but was more toxic; 6 of 15 patients (40%) developed esophagitis (Grade 3 in 5 patients, Grade 4 in 1 patient), and 45% of all episodes of Grade 3/4 leukopenia occurred during concurrent therapy. Other nonhematologic toxicity was uncommon. Twenty-nine of 38 patients (76%) achieved a partial or complete response to treatment (limited stage, 14 of 15 patients, 93%; extensive stage, 15 of 23 patients, 65%). The complete response rate was 26% (limited stage disease, 40% versus extensive stage disease, 17%). Median actuarial overall survival was 7 months for patients with extensive stage disease, and 17 months for patients with limited stage disease. Prophylactic whole brain irradiation was not used, and seven patients developed brain metastases as their initial site of relapse.

CONCLUSIONS

The combination of paclitaxel, administered by 1-hour infusion, carboplatin and extended schedule etoposide is feasible and well tolerated in the doses administered in this Phase II trail. This regimen was highly active with treatment results comparable to other standard regimens. Increased doses of both paclitaxel and carboplatin could probably be tolerated and are currently being evaluated. Precise definition of the role of paclitaxel in the treatment of small cell lung carcinoma awaits the results of randomized studies.