Autologous Bone Marrow Transplantation - Blog Science Connections

Etoposide and Cisplatin for Lung Cancer 517
Table 1. Treatment Schema for High-Oose Etoposide, High-Dose Cisplatin, and
Autologous Marrow Reinfusion
Agent -7 -6 -5 -4 -3 -2 -1 0 +1
Day
Continuous saline x x x x x x x
infusion i.v.
Cisplatin 40 mg/m 2 /day x x x x x
i.v. x 5 days
Mannitol 25 g i.v. x x x x x
Etoposide 8 600 mg/m 2 /day i.v. x x x
via syringe pump x 3 days
Autologous bone marrow
infusion
x
"Starting dose etoposide increased stepwise.
cisplatin and continuing until 24 hours after the final dose. Cisplatin, 250 ml
in 3% saline, was infused intravenously over 3 hours, followed immediately by
25 g mannitol. Cisplatin was administered at a dosage of 40 mg/m 2 / day for 5
consecutive days, or a total dosage of 200 mg/m 2
(days T-6 through T-2).
Etoposide was drawn into a syringe and infused directly into a central
venous catheter using an infusion syringe pump (30). Etoposide (1800
mg/m 2 ) was chosen as the initial dose. One third of the total dose, or 600
mg/m 2 /day, was administered each day for 3 consecutive days (days T-6
through T-4). The total dose of etoposide in mg/m 2 , therefore, is the sum of
the 3 consecutive daily doses. Subsequently escalated doses were 2400,
3000, and 3600 mg/m 2 . Groups of at least four patients were entered at each
dose level. Patients then were observed for signs of toxicity for a minimum of
4 weeks.
RESULTS
Evaluation of etoposide at four dose levels (1800,2400,3000, and 3600
mg/m 2 ) has been completed; the maximum tolerated dose has not yet been
reached (Table 2). Three of 15 patients died within 3 weeks of transplant, two
owing to tumor progression and infection (despite normal recovery of WBC
and polymorphonuclear cell counts) and one owing to infection alone. These
three patients are inevaluable for antitumor response.
Toxicities due to high-dose etoposide and high-dose cisplatin therapy
consisted of nausea and vomiting (in almost half the patients) but were mild
to moderate and well controlled by antiemetics. A moderate to severe degree
of alopecia occurred in most patients. Three patients had profound highfrequency
hearing loss, which has persisted for several months, probably as a
result of cisplatin-induced acoustic nerve damage. Fever, chills, metabolic