Practice guideline for the role of combination chemotherapy in the initial management of limited-stage small-cell lung cancer

An evidence-based practice guideline was developed to identify the optimal combination chemotherapy regimen, schedule of administration, and duration of therapy for the first-line treatment of adults with limited-stage small-cell lung cancer. The guideline is based on a systematic search and review of literature published between 1985 and December 2002. Three reviewers selected studies for inclusion in the guideline according to pre-defined criteria. Fifty randomized controlled trials, five in abstract form, were included in the review, and feedback on a draft version of the guideline was obtained from medical oncologists in the province of Ontario, Canada. The most commonly used regimens in clinical trials are cyclophosphamide-doxorubicin(Adriamycin)-vincristine, and etoposide-cisplatin. No combination chemotherapeutic regimen has been conclusively shown to be superior to either of these regimens. Most studies comparing chemoradiation regimens used sequential rather than concurrent thoracic radiotherapy. When treating for cure with chemoradiation, there is evidence from one randomized controlled trial to support the use of etoposide-cisplatin over an anthracycline-containing regimen. There is conflicting evidence concerning a survival advantage for a regimen that alternates cyclophosphamide-doxorubicin-vincristine with etoposide-cisplatin compared with either regimen alone. If bolus etoposide-cisplatin is the treatment of choice, evidence from one randomized trial suggests that the optimal sequence of administration is cisplatin followed by etoposide. The use of maintenance chemotherapy is not indicated. There is insufficient evidence to support the routine use of dose-intensive regimens outside a clinical trial, to determine the optimal duration of chemotherapy, or to support the routine substitution of carboplatin for cisplatin in combination chemotherapy regimens in this patient population. RECOMMENDATIONS: Etoposide-cisplatin is the preferred chemotherapy regimen for patients with limited-stage small-cell lung cancer when concurrent thoracic radiotherapy is used. It is reasonable to offer the alternation of etoposide-cisplatin with cyclophosphamide-doxorubicin-vincristine, provided the administration of radiotherapy concurrent with an anthracycline is avoided.