Reviewers: Li Liu, MD
Source: Journal of Clinical Oncology, Volume 17, No 8 (August):2300-2308, 1999
Despite decades of intensive investigation using various combinations of chemotherapy, the outcome of patients with extensive-stage small cell lung cancer (ESCLC) remains poor. . Even so small-cell lung cancer is a highly responsive tumor sensitive to a broad spectrum of cytotoxic agents. Numerous dose escalation and dose-intensity trials with various antineoplastic agents have been attempted. However, to date, higher complete remission rates have not translated into better survival. This is a report of a randomized intergroup trial to compare an intensive chemotherapy regimen plus irradiation versus standard chemotherapy for the treatment of ESCLC.
Eligibility criterion included age younger than 68, performance status of 0 to 2, and freedom from brain metastases. Patients were randomized to either cisplatin, vincristine, doxorubicin, and etoposide (CODE) or alternating cyclophosphamide, doxorubicin, vincristine/etoposide and cisplatin (CAV/EP). Patients on the CODE arm who achieved a complete response (CR) or a partial response (PR) at the primary site and a CR at all known metastatic sites were to receive both consolidative thoracic irradiation (TI) and prophylactic cranial irradiation (PCI). PCI was given to patients with CR to the CAV/EP regimen, whereas TI was optional.
A total of 109 on the CAV/EP arm and 110 on the CODE arm were eligible for analysis. More than 70% of all patients received the intended protocol chemotherapy on both arms.
Due to the high treatment-related fatality rate in the CODE arm, the study was terminated before the intended sample size was reduced. Dose-intense chemotherapy again showed no benefit in survival for patients with ESCLC despite higher response rates compared with standard chemotherapy. Future success in improving outcome of ESCLC may rely on better understanding of the underlying biology of this malignancy and the development of new therapeutic agents.