Correspondence

Bone Marrow Transplantation

N Engl J Med 1994; 331:617September 1, 1994

Article

To the Editor:

In his review on bone marrow transplantation (March 24 issue),1 Dr. Armitage has provided an excellent overview of transplantation therapy for hematologic cancers, with a brief discussion of preliminary results when the technique is used for solid tumors. He stated that “for the treatment of... small-cell lung cancer, the results of transplantation have been sufficiently discouraging to preclude further clinical trials.”

Previous trials of high-dose therapy for small-cell lung cancer were noted for their high mortality rates, frequent use of single agents in high doses, or lack of chest radiotherapy, resulting in relatively poor overall results and high rates of local and regional relapse. In the only randomized trial performed to date, Humblet et al. reported a modest improvement in disease-free survival (P = 0.002) and a trend toward overall survival (P = 0.13) in patients with small-cell lung cancer in first response who receive high-dose therapy2. A dose-response relation is unequivocally demonstrated in this trial. Notably, of 16 patients with limited-stage cancer who were undergoing transplantation, 13 had relapses in the chest resulting from the failure to administer chest radiotherapy.

In this day of cost consciousness and cost efficiency, we must be ever more responsible with respect to the types of clinical research trials performed. In no situation is this more relevant than in the area of high-dose therapy, which has been targeted by third-party payers as an area to reduce costs and restrict entry into clinical trials. Incautious comments on the part of review authors can be taken out of context and used to deny participation in clinical trials.

As reported previously,3 my colleagues and I have had encouraging results in a phase II trial of treatment of patients with limited-stage small-cell lung cancer. Of 14 patients with complete or nearly complete responses, 2-year event-free survival was 57 percent, with a median follow-up of 15 months without therapy (range, 4 to 69). High-dose chemotherapy with autologous hematopoietic stem-cell support is worthy of further study in small-cell lung cancer.

Anthony Elias, M.D.
Harvard Medical School, Boston, MA 02115

3 References

1. 1

   Armitage JO. Bone marrow transplantation. N Engl J Med 1994;330:827-838
   Full Text | Web of Science | Medline

2. 2

   Humblet Y, Symann M, Bosly A, et al. Late intensification chemotherapy with autologous bone marrow transplantation in selected small-cell carcinoma of the lung: a randomized study. J Clin Oncol 1987;5:1864-1873
   Web of Science | Medline

3. 3

   Elias AD, Ayash L, Frei E III, et al. Intensive combined modality therapy for limited-stage small-cell lung cancer. J Natl Cancer Inst 1993;85:559-566
   CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Armitage replies:

To the Editor: Dr. Elias points out an important practical problem regarding the application of high-dose therapy and bone marrow transplantation to the treatment of patients with so-called solid tumors. Dr. Elias provides data for small-cell cancer of the lung, but similar results are available for breast cancer and some other common tumors. High-dose therapy and bone marrow transplantation often yield an increased response rate, a modest increase in median disease-free or overall survival, but no increase, or a marginal one, in the cure rate. In these disorders the debate about the use of bone marrow transplantation will increasingly focus on issues of value versus cost, quality of life, and so on.

With modern techniques, autologous bone marrow transplantation can be performed mostly or entirely as an outpatient procedure, with a dramatic reduction in cost, morbidity, and mortality from what had been seen previously. Since this treatment can be completed relatively quickly, it might be preferred by some patients and physicians even if it produced the same results as chemotherapy administered in a more traditional way over a longer period. Who will be allowed to decide which options are available is an important and unanswered question about our future health care system.

James O. Armitage, M.D.
University of Nebraska Medical Center, Omaha, NE 68198-3332