Treatment of extensive stage small cell bronchogenic carcinoma. Effects of variation in intensity of induction chemotherapy.

Forty-nine consecutive previously untreated patients with extensive stage small cell bronchogenic carcinoma were treated with cyclophosphamide 1,000 mg/m2, doxorubicin 50 mg/m2, etoposide (VP-16-213) 125 mg/m2, and vincristine 1.4 mg/m2 (maximum 2 mg) as induction chemotherapy. Thirty-four patients were given high-intensity therapy, receiving these drugs on both Days 1 and 8 of two or three 21-day induction courses. Fifteen other patients were treated with moderate intensity, receiving these drugs only on Day 1 of two 21-day induction courses. The number and intensity of induction courses were determined by the time of entry into the study. There were 31 complete or partial remissions among the 33 evaluable patients treated with high-intensity therapy (94 percent), including eight complete remissions (24 percent), whereas there were 11 responses (73 percent) including three complete responses (20 percent) among the 15 patients treated with moderate-intensity therapy. There was no marked tendency for the patients in the high-intensity group to have a more favorable response to the induction chemotherapy (p = 0.22), and survival experience was very similar in the two groups (p = 0.92). Overall median survival was 12 months. Within the high-intensity group, there was no significant difference between patients receiving two or three courses of induction therapy with respect to response (p = 0.97) or survival (p = 0.32). There were six induction deaths in the high-intensity induction group (18 percent) and one induction death in the moderate-intensity group (7 percent) (p = 0.59). In addition to the expected hematologic and infectious complications, there were unexpectedly high frequencies of mucositis, reversible congestive heart failure, and severe peripheral neuropathy in patients treated with high-intensity induction. Only two patients, both in the high-intensity group, were alive and free of disease at 24 months. Increasing the intensity of induction chemotherapy with these drugs did not significantly improve response or survival in extensive stage small cell bronchogenic carcinoma.

The clinical behavior of "mixed" small cell/large cell bronchogenic carcinoma compared to "pure" small cell subtypes.

Biopsy specimens from 19 previously untreated lung cancer patients were prospectively diagnosed as small cell carcinoma with a large cell component. The patients were thoroughly staged and received intensive combination chemotherapy. They represented 12% of all small cell carcinoma cases eligible for aggressive chemotherapy protocols during a 5.5 year period. To determine whether the clinical behavior of this "mixed" histologic variant differed from the other histologic subtypes of small cell lung cancer, we compared these 19 patients to a concurrent group of 103 patients with only small cell cancer in their diagnostic biopsies given equivalent therapy. The "mixed" histology patients were comparable to the "pure" small cell group in age, performance status, extent of disease, and frequency of bone marrow, liver, bone, and central nervous system metastases. Their complete plus partial response rare (58%) was significantly less than the response rate for the "pure" small cell patients (91%), their complete response rate was also lower (16 versus 46%), and their overall survival was significantly shorter (median, 6 versus 10.5 months) Mixed histology small cell/large cell carcinoma represents a distinct pathologic variant of small cell carcinoma of the lung, associated with lower response rates and shorter survival than the "pure" small cell subtypes. Since combination chemotherapy yields some complete responses and long-term disease-free survival in these patients, however, aggressive treatment with potentially curative intent should be considered in their management.