Autologous Bone Marrow Transplantation - Blog Science Connections

High-Dose Etoposide and Cisplatin With
Autologous Bone Marrow Support as
Treatment for Lung Cancer
Hillard M. Lazarus and Thomas R. Spitzer
Etoposide or VP-16-213, a semisynthetic congener of podophyllotoxin, is a drug
important in the treatment of several human malignancies, including testicular
and small cell lung cancer, leukemia, lymphoma, and Kaposi's sarcoma
associated with the acquired immunodeficiency syndrome (AIDS) (1,2). Early
trials using etoposide indicated that myelosuppression was the dose-limiting
toxicity, although it was of modest degree and short duration (2-4). For ionizing
radiation and a number of cytotoxic drugs including melphalan, thio-TEPA,
cisplatin, 5-fluorouracil, and methotrexate, an escalation of drug dosage usually
leads to an increased antitumor effect (5-13).
Given the reality of improved supportive care and the suggestion of a
dose-response effect, several investigators undertook significant escalations in
etoposide dose (with or without reinfusing autologous marrow) (14-17).
Mucositis and toxicity to the marrow were severe, but antitumor responses were
noted in several patients with advanced cancer. In addition, etoposide has
exhibited synergistic activity with cisplatin and other antineoplastic agents in
several human and animal tumor systems (1,18-21). Etoposide and cisplatin
together are effective therapy for both small cell and non-small cell lung cancers
(22-27). For these reasons we undertook a phase 1 trial in patients with
575