Weekly alternating non-cross-resistant chemotherapy for small cell lung cancer with a good prognosis - A study of the Hellenic Cooperative Oncology Group

This trial was conducted by the Hellenic Cooperative Oncology Group to impr ove the responses and survival in small cell lung cancer with a good progno sis, using a weekly intensive chemotherapy with alternated non-cross-resist ant myelosuppressive agents. Patients were classified into two groups; grou p A consisted of those who received the initial designed regimen (29 patien ts), and group B consisted of those who received the more intensified regim en that increased by 25% the doses of carboplatin, epirubicin, and ifosfami de, and by 33% the doses of etoposide given on days 1, 2, and 3 with prophy lactic granulocyte colony-stimulating factor support. Chemotherapy in group A consisted of carboplatin 150 mg/m(2) in 250 mi of 5% dextrose in water a s an I-hour infusion on day 1, etoposide 75 mg/m(2) in 250 mi normal saline as an I-hour infusion on days 1 and 2 alternating with epirubicin 30 mg/m( 2) intravenous push on day 8, and ifosfamide 2 g/m(2) in 500 mi 5% dextrose in water as a 2-hour infusion with mesna protection on day 8. Responding p atients with limited disease were also treated with thoracic irradiation. T hose who achieved complete response received prophylactic cranial radiother apy. In group A, the overall response rate was 79.3%, with a 27.6% complete response rate, a median time to progression of 5.71 months, and a median s urvival of 8.3 months. For patients with limited disease, the response rate was 75%, with a 40% complete response rate, a median time to progression o f 5.87 months, and a median survival of 10.98 months. The respective number s for extensive disease were 89% (only partial responses), 4.82 months, and 5.67 months. The toxicity was mild and manageable. There were no dose redu ctions or treatment delays. In view of the excellent tolerability and the r ather low efficacy of the initial regimen, we decided to administer the mor e intensified one with granulocyte colony-stimulating factor support. In Gr oup B, the overall response rate was 91.8%, with a 45.9% complete response rate, a median time to progression of 7.05 months, and a median survival of 10.16 months. For limited disease, the response rate was 93%, with a 52% c omplete response rate, a median time to progression of 7.05 months, and a m edian survival of 10.49 months. The respective numbers for extensive diseas e were 88% (25% complete response), 6.82 months, and 9.02 months. The toxic ity of this more intensified regimen was more severe but acceptable. Myelos uppression was the main toxicity. However, grade 3-4 febrile neutropenia re quiring hospitalization occurred only in 6% of patients. The relative dose intensity was 91%, probably the result of the prophylactic use of granulocy te colony-stimulating factor. The differences in response rate, time to pro gression, and survival were not statistically significant between the two g roups. There were statistically significant differences in the response rat e (p = 0.019) and survival rate (p = 0.001) between limited disease and ext ensive disease only in group A. In conclusion, this weekly, alternated regi men, specifically the intensified regimen, appears to be very active and we ll tolerated in patient who have small cell lung cancer with a good prognos is. However, despite the high efficacy, this study failed to show any survi val advantage as compared with that obtained with the standard treatment fo r small cell lung cancer.