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.
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.
Authors: Daniel C Colvin; Mary E Loveless; Mark D Does; Zou Yue; Thomas E Yankeelov; John C Gore Journal: Magn Reson Imaging Date: 2010-12-28 Impact factor: 2.546
Authors: W Eberhardt; G Stamatis; M Stuschke; H Wilke; M R Müller; S Kolks; M Flasshove; J Schütte; M Stahl; L Schlenger; V Budach; D Greschuchna; G Stüben; H Teschler; H Sack; S Seeber Journal: Br J Cancer Date: 1999-12 Impact factor: 7.640
Authors: S Leyvraz; N Ketterer; L Perey; J Bauer; P Vuichard; J P Grob; P Schneider; V von Fliedner; F Lejeune; F Bachmann Journal: Br J Cancer Date: 1995-07 Impact factor: 7.640