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Introduction: To determine the 1-year survival, response rate, and toxicity for patients with limited stage small cell lung cancer treated with the combination of cisplatin plus etoposide plus paclitaxel with delayed concurrent (starting with cycle 3) high dose thoracic radiotherapy., Patients and Methods: Patients with previously untreated limited stage small cell lung cancer, Easter Cooperative Oncology Group performance status of 0-2 and adequate organ function were eligible. Cycles 1 and 2 of chemotherapy consisted of paclitaxel 170 mg/m intravenous day 1, etoposide 80 mg/m intravenous days 1 to 3, and cisplatin 60 mg/m intravenous day 1 followed by filgrastim 5 microg/kg subcutaneously days 4 to 13. Cycles 3 and 4 of chemotherapy consisted of a reduced dose of paclitaxel 135 mg/m intravenous day 1, and the same dose of etoposide and cisplatin with concurrent thoracic radiation therapy 1.8 Gy in 35 fractions (total 63 Gy) administered over 7 weeks., Results: Sixty-three patients were entered, 61 patients were eligible. The most common grade 4 toxicity seen was granulocytopenia (62%). Nonhematologic toxicities included febrile neutropenia in 19% of patients, grade 3 and 4 esophagitis in 32% of patients, and grade 3 peripheral neuropathy in 14% of patients. Two patients suffered lethal toxicities. The overall response rate was 79%. The 1-year survival rate was 64%. The median overall survival was 15.7 months, and the median progression-free survival was 8.6 months., Conclusions: The combination of cisplatin plus etoposide plus paclitaxel chemotherapy and concurrent delayed thoracic radiotherapy as administered in this trial provide no apparent advantage with respect to response, local control, or survival compared with historical controls.

Forty-four specimens of non-malignant and malignant human lung tissue, taken from patients with non-small cell lung cancer (NSCLC), were examined for the expression of wild-type p53, mutant p53, and bcl-2 and the occurrence of programmed cell death (apoptosis). Wild-type p53 expression peaked in peritumoral and metaplastic samples, whereas mutant p53, bcl-2 and apoptosis were first detected in metaplasia and increased with progression to carcinoma. Bcl-2 positive samples had lower levels of apoptosis than bcl-2 negative samples and was independent of wild-type or mutant p53 expression. These results suggest that the over-expression of wild-type p53 may be an early cellular response to an alteration in normal cellular homeostasis. The ensuing increase in apoptosis appears to be relatively independent of mutant or wild-type p53 expression, but does not occur in cells expressing bcl-2.