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Previous Volume 328:756-761 March 18, 1993 Number 11 Next

The Effects of Treatment with Interleukin-1 on Platelet Recovery after High-Dose Carboplatin

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ABSTRACT

Background Thrombocytopenia is a frequent side effect of cancer chemotherapy and commonly limits attempts to escalate drug doses. To determine whether interleukin-1 could ameliorate carboplatin-induced thrombocytopenia, we combined it with high-dose carboplatin in 43 patients with advanced neoplasms.

Methods High-dose carboplatin (800 mg per square meter of body-surface area) was administered alone to a control group. Subsequent patients were randomly assigned to receive the same dose of carboplatin with interleukin-1, administered either before or after carboplatin. Interleukin-1 was given intravenously at a dose of 0.03, 0.1, or 0.3 µg per kilogram of body weight per day for five days.

Results Carboplatin alone consistently produced thrombocytopenia with a median nadir of 19,000 platelets per cubic millimeter and a median of 10 days with less than 100,000 platelets per cubic millimeter. All 15 patients receiving interleukin-1 before carboplatin had similar findings. In contrast, 5 of the 15 patients given one of the two higher doses of interleukin-1 after carboplatin had minimal thrombocytopenia (nadir, 91,000 to 332,000 platelets per cubic millimeter). In the 10 patients given 0.3 µg of interleukin-1 per kilogram after carboplatin treatment, the platelet count recovered to 100,000 per cubic millimeter significantly earlier than in either the control group (P = 0.002) or the patients who received interleukin-1 before carboplatin (P = 0.003), with the median times to recovery in the three groups being 16, 21, and 23 days, respectively. At the highest dose of interleukin-1, toxicity was substantial (but reversible), requiring inpatient support for hypotension, supraventricular arrhythmias, and pulmonary-capillary leak.

Conclusions Interleukin-1 can accelerate the recovery of platelets after high-dose carboplatin therapy and may be clinically useful in preventing or treating thrombocytopenia induced by chemotherapy.

Source Information

From the Biological Response Modifiers Program (J.W.S., D.L.L., J.E.J., W.H.S., B.L.G., B.D.C., S.P.C., J.T.H., R.G.F., J.J.O.) and Data Management Services (W.G.A.), Frederick Cancer Research and Development Center of the National Cancer Institute; Frederick Memorial Hospital (S.J.F., J.C.H.); and Program Resources, Inc./DynCorp. (G.C.P., W.J.U.) -- all in Frederick, Md.; the Cancer Treatment Evaluation Program, National Cancer Institute, Rockville, Md. (M. Sznol, L.L.M.); and Dainippon Pharmaceutical Co., Osaka, Japan (M. Shimizu).

Address reprint requests to Dr. Smith at NCI-FCRDC, BRMP, 501 W. Seventh St. Suite 3, Frederick, MD 21701.

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