Smallcell Lung Cancer

Most patients with small-cell lung cancer (SCLC) respond to chemotherapy, but such responses are usually of relatively short duration, and survival has not significantly increased over the past two decades, either in limited or in extensive disease. These discouraging results prompted the investigation of high-dose chemotherapy with autologous stem cell transplant (ASCT) in the early 1980s. Initial studies testing one or two high-dose chemotherapy cycles as front-line therapy showed no improvement in outcome compared to historical controls.39-42 Subsequently, delayed highdose chemotherapy with ASCT was tested as consolidation therapy for a response obtained with conventional-dose chemotherapy. Spitzer et al.43 reported

4-year OS of 19% among 32 such patients with limited disease (LD). There is only one reported randomized trial of HDC in SCLC.44 Patients responding to induction chemotherapy were randomized to one additional cycle or to high-dose cyclophosphamide/BCNU/ etoposide with ASCT. Although patients received cranial irradiation, no chest RT was delivered. The transplant arm showed improved responses and EFS, but OS was not significantly different between both groups, in part due to a 17% TRM rate on the high-dose arm. All patients with extensive disease (ED) relapsed in both arms of the study.

Subsequent studies incorporated thoracic and cranial RT after transplant. Elias et al.45 treated 36 LD patients with a sequence of induction therapy, highdose chemotherapy with cyclophosphamide/cisplatin/ BCNU, and chest and cranial RT after hematologic recovery. Median EFS was 21 months, with a 5-year OS of 41%. All seven patients transplanted in partial response to induction therapy relapsed. However, the

5-year progression-free survival (PFS) was 53% for the

29 patients transplanted in CR.Leyvraz et al.46 from the EBMT treated 69 patients (30 with LD and 39 with ED) with three sequential courses of high-dose chemotherapy (ifosfamide, carboplatin, and etoposide) with ASCT as initial therapy. RT, not required but recommended for responders, was administered to 37 patients to the chest, and prophylactically to the brain to 24 patients. Predictably, patients with LD had better outcome than those with ED, with a median OS of 18 months vs 11 months, and 2-year OS rates of 32% vs 5%.

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