Autologous Bone Marrow Transplantation - Blog Science Connections

590 Intensive use of Carmustine
Pulmonary toxicity seems to be greater when carmustine is given in a brief,
intensive schedule with bone marrow transplantation, compared with the
same dose in a conventional schedule (2). Severe hepatotoxicity and
neurotoxicity appeared at higher doses.
During the phase I study and subsequent phase II trial, impressive
antitumor responses occurred in several types of tumors, including melanoma,
glioblastoma, small cell carcinoma of the lung, and metastatic tumors
of the central nervous system.
unfortunately, attempts to exploit this single-agent activity by combining
carmustine with other agents have not been overly successful. For instance,
Herzig (3) reported on the use of carmustine at doses of 600-1200 mg/m 2
and melphalan at 90-180 mg/m 2
in treating metastatic melanoma. The
complete and overall response rates of 10% and 59%, respectively, were not
superior to those observed with either single-agent carmustine (4) or
melphalan (5). Moreover, pulmonary toxicity seemed to increase with the
higher doses of this regimen. Peters etal. (6) experienced difficulty with their
intensive combination-chemotherapy regimens that include carmustine at
600-750 mg/m 2 . The subsequent deletion of carmustine, cisplatin, cyclophosphamide
plus melphalan, and carmustine, cyclophosphamide, cisplatin
plus etoposide produced altered, often diminished, patterns of renal and
hepatic toxicity, respectively (Peters et ai, personal communication).
We are currently attempting to give total carmustine doses of 1200-1800
mg/m 2
in two or three "fractionated" courses over several months. This will
be successful only if damage is not invariably cumulative.
In summary, carmustine monochemotherapy with ABMT is not likely to
find a major place in antineoplastic therapy; the doses required to provide a
measure of tumor control are probably too toxic. Although there are
problems with the combinations noted above, carmustine probably is still
useful, especially for treating tumors for which carmustine is active at a
conventional dose. Examples include the malignant gliomas, Hodgkin's
disease, and perhaps certain other tumors. In any case, it is unlikely that a
carmustine dose of more than 600-750 mg/m 2
can be given without
incurring an at least 10% incidence of severe interstitial pneumonia.
REFERENCES
1. Phillips GL, Fay JW, Herzig GP, Herzig RH, Weiner RS, Wolff SN, Lazarus HM, Karanes C,
Ross WE, Kramer BS, The Southeastern Cancer Study Group. Cancer 1983;52:1792.
2. Weinstein AS, Diener-West M, Nelson DF, Pakuris E. Cancer Treat Rep 1986;70:943.
3. Herzig RH. In Management of Advanced Melanoma, NathansonL, ed. Churchill-Livingstone,
New York, 1986:71.
4. Fay JW, Levine MN, Phillips GL, Herzig GP, Herzig RH, Lazarus HM, Wolff SN, Weiner RS.
Proceedings of the American Association for Cancer Research/American Society of Clinical
Oncology 1981 ;17:532.
5. Lazarus HM, Herzig RH, Graham-Pole J, Wolff SN, Phillips GL, Strandjord S, Hurd D,
Forman W, Gordon EM, Coccia P, Gross S, Herzig GP. J Clin Oncol 1983;1:359.