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Dose-Intensive Therapy for Limited-Stage Small-Cell Lung Cancer: Long-Term Outcome

From the Department of Medicine, Division of Biostatistics, Dana-Farber Cancer Institute; and the Department of Medicine, Beth Israel Hospital, Harvard Medical School, Boston, MA.

Address reprint requests to Anthony Elias, MD, Harvard Medical School, Department of Medicine, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115; email anthony_elias{at}macmailgw.dfci.harvard.edu

PURPOSE: To determine progression-free survival (PFS) and overall long-term survival for limited-stage small-cell lung cancer (SCLC) patients aged 60 years or younger who respond to first-line chemotherapy followed by high-dose combination alkylating agents (cyclophosphamide 5,625 mg/m², cisplatin 165 mg/m², and carmustine 480 mg/m²) with hematologic stem-cell support and chest and prophylactic cranial radiotherapy.

PATIENTS AND METHODS: Patients were selected on the basis of their continued response to first-line therapy, their relative lack of significant comorbidity, and their ability to obtain financial clearance.

RESULTS: Of 36 patients with stage III SCLC, nine patients (25%) had achieved a complete response (CR), 20 had achieved a near-CR, and seven had achieved a partial response before undergoing high-dose therapy. Toxicity included three deaths (8%). For all patients, the median PFS was 21 months. The 2- and 5-year survival rates after dose intensification were 53% (95% confidence interval [CI], 39% to 72%), and 41% (95% CI, 28% to 61%). Of the 29 patients who were in or near CR before undergoing high-dose therapy, 14 remain continuously progression-free a median of 61 months (range, 40 to 139 months) after high-dose therapy. Actuarial 2- and 5-year PFS rates were 57% (95% CI, 41% to 79%) and 53% (95% CI, 38% to 76%). By multivariate analysis, short intensive induction chemotherapy was associated with favorable outcome (P < .05).

CONCLUSION: Use of high-dose systemic therapy with intensive local-regional radiotherapy was associated with manageable treatment-related morbidity and mortality. Patients who were in or near CR before intensification are enjoying an unmaintained 5-year PFS rate of 53%. Late complications were infrequent, and most patients returned to full-time work and activity. A randomized comparison of this approach and conventional-dose therapy should define the use of dose intensification with hematopoietic support in patients with responding limited-stage SCLC.

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