Original Guideline: March 2001
Members of the Lung Disease Site Group (DSG) felt that the literature that had been reviewed and collated for this guideline was so extensive that it needed to be presented in a very concise format. This was done by using tables to summarize data, with careful attention to avoid duplicating information in the text and the tables. The recommendations were written to clarify that the guideline concerned first-line therapy only. The Lung DSG felt that second-line therapy should be the subject of a separate guideline. As a guideline providing recommendations on the role of radiotherapy in limited small-cell lung cancer had been previously completed, the DSG felt that a reference should be made to this document, as well as to the guideline under development on the role of prophylactic chemotherapy in patients who achieve complete response after therapy for small-cell lung cancer (SCLC). During its deliberations, the members of the Lung DSG had discussed the need to present information on the biological equivalence of cisplatin and carboplatin in small-cell lung cancer. The draft document sent for practitioner feedback made reference to the equivalence of etoposide-cisplatin and etoposide-carboplatin. However, there were no data presented in the document to support a recommendation that these regimens were equivalent; practitioners commented on this lack of supporting evidence. In fact, the only trial that compared these two regimens head-to-head had been removed from an earlier draft because the trial did not report survival data for patients with limited-disease SCLC. This trial by Skarlos et al randomized 143 eligible limited- and extensive-disease SCLC patients to either etoposide-cisplatin or to etoposide-carboplatin; 41 patients with limited disease were randomized to each arm. The overall survival of patients on the two treatment arms was similar, but data on the survival of patients with limited disease were not presented. The trial was clearly underpowered to prove equivalence of the two treatment regimens in either limited or extensive disease. Following further discussion of this trial at a Lung DSG meeting, and in the absence of other data, it was decided to remove the reference that etoposide-carboplatin was biologically equivalent to etoposide-cisplatin from the Recommendation section and to discuss the limited amount of data available on this issue in the Consensus section.
Members of the DSG discussed extensively the issue of the number of treatment cycles that patients with small-cell lung cancer should receive. It was recognized that most of the clinical trials on which the recommendations in this guideline are based used six cycles of chemotherapy. However, the trend in clinical practice increasingly has been to use only four cycles of cisplatinum-based chemotherapy. Lung DSG members felt that a statement acknowledging this difference should be included in the recommendations.
December 2003 Update:
The Lung DSG noted the discrepancy between the original guideline recommendations and current practice in North America, where etoposide-cisplatin (EP) along with concurrent radiation is generally considered optimal treatment for limited-stage SCLC. They also noted that there is evidence for the superiority of EP over cyclophosphamide-adriamycin-vincristine (CAV) in the treatment of extensive-stage SCLC. In reviewing the data from the two meta-analyses and the trial by Sundstrom et al, the DSG agreed that the weight of evidence supports the use of EP over cyclophosphamide-adriamycin-vincristine, particularly where concurrent radiotherapy will be administered.
The evidence for intensification of the dose of chemotherapy was also discussed. However, although a few individual trials have demonstrated a survival benefit to a dose-intensive regimen over a standard regimen, the data are conflicting, and no clear and consistent advantage exists. The DSG agreed that only selected patients with limited-stage SCLC would be suitable for a dose-intensive approach and, therefore, dose-intensive regimens should only be used in the context of a clinical trial.
