© 1993 by Oxford University Press
Journal of the National Cancer Institute, Vol. 85, No. 7, 559-566,
April 7, 1993
© 1993 Oxford University Press
Intensive Combined Modality Therapy for Limited-Stage Small-Cell Lung Cancer
Department of Medicine Boston, Mass
Division of Biostatistics Boston, Mass
Division of Radiation Therapy, Dana-Farber Cancer Institute Boston, Mass
Beth Isreal Hospital, Harvard Medical School Boston, Mass
Anthony Elias, M.D., Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115.
BACKGROUND:: Conventional-dose chemotherapy for small-cell lung cancer has resulted in high response rates but rarely in a cure. The addition of thoracic radiotherapy (chemoradiotherapy) has improved survival for patients having limited disease, resulting in a median survival of 14–18 months. Previous trials evaluating high-dose chemotherapy and autologous bone marrow transplantation have demonstrated enhanced complete response rates without documenting overall survival benefit.
PURPOSE:: The purpose of this phase II trial was to determine the disease-free and overall survival, toxic effects, and relapse patterns in patients with limited small-cell lung cancer who were in partial or complete response to first-line conventional-dose chemotherapy and then received intensive systemic combined modality therapy.
METHODS:: Adults with stage III small-cell lung cancer who had achieved at least a partial response to conventional-dose induction chemotherapy were treated with high-dose cyclophosphamide, cisplatin, and carmustine combined with autologous bone marrow transplantation. Cumulative doses of the three drugs were 5625, 165, and 480 mg/m2, respectively. After recovery, patients received thoracic radiotherapy (50–60 Gy in 25–30 fractions over 5–6 weeks) and cranial radiotherapy (30 Gy in 15 fractions during 3 weeks).
RESULTS:: Of 19 patients in the study, six had achieved complete response, eight had a greater than 90% reduction in tumor size, and five had a 50%-90% reduction in tumor size. After high-dose therapy, 15 of the 19 were in complete response. Overall, median time to treatment failure after high-dose therapy was 12 months. Overall survival was 73% (95% confidence interval [CI] = 42%-89%) at 1 year and 53% (95% CI = 22%–77%) at 2 years. Of the 14 patients in or near complete response before high-dose therapy, 10 remain disease free with no further chemotherapy a median of 15 (4·69+) months after therapy. Actuarial 2-year disease-free survival is 57% (95% CI = 20%–82%). One patient died of Candida sepsis. Morbidity was low, and most patients returned to full-time work. With the exception of herpes zoster, there were no complications more than 3 months after high-dose therapy.
CONCLUSIONS:: The majority of the patients in this study are experiencing prolonged and unmaintained disease-free survival. Our findings suggest that patients in or near complete response before high-dose therapy have the most favorable prognosis.
IMPLICATIONS: A randomized comparison between this approach and conventional-dose therapy is planned to define the utility of dose intensification with autologous bone marrow transplantation in the treatment of patients with limited-stage small-cell lung cancer who are in or near complete response.
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