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

John W. Smith, Dan L. Longo, W. Gregory Alvord, John Edward Janik, William H. Sharfman, Barry L. Gause, Brendan D. Curti, Stephen P. Creekmore, Jon T. Holmlund, Robert G. Fenton, Mario Sznol, Langdon L. Miller, Masanao Shimizu, Joost J. Oppenheim, Shelby J. Fiem, Jean C. Hursey, Gerry C. Powers, Walter J. Urba

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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-1α 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-1α, administered either before or after carboplatin. Interleukin-1α 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-1α before carboplatin had similar findings. In contrast, 5 of the 15 patients given one of the two higher doses of interleukin-1α 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-1α 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-1α 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-1α, toxicity was substantial (but reversible), requiring inpatient support for hypotension, supraventricular arrhythmias, and pulmonary-capillary leak. Conclusions: Interleukin-1α can accelerate the recovery of platelets after high-dose carboplatin therapy and may be clinically useful in preventing or treating thrombocytopenia induced by chemotherapy., Escalation of the dose of many antineoplastic drugs is limited by granulocytopenia and thrombocytopenia. Although colony-stimulating factors1,2 and the transplantation of bone marrow or peripheral-blood progenitor cells36 have had an effect on this problem, there are currently no strategies that permit repeated cycles of high-dose chemotherapy. Thrombocytopenia is not affected by granulocyte colony-stimulating factor1 or granulocyte-macrophage colony-stimulating factor2 and rapidly becomes dose-limiting after only moderate increments in chemotherapy despite the use of these factors. However, phase I studies of interleukin-1b7,8 and interleukin-1a9 have demonstrated that they cause platelet counts to become elevated one to two weeks after…

Original languageEnglish (US)
Pages (from-to)756-761
Number of pages6
JournalNew England Journal of Medicine
Volume328
Issue number11
DOIs
StatePublished - Mar 18 1993

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  • Medicine(all)

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Smith, J. W., Longo, D. L., Alvord, W. G., Janik, J. E., Sharfman, W. H., Gause, B. L., Curti, B. D., Creekmore, S. P., Holmlund, J. T., Fenton, R. G., Sznol, M., Miller, L. L., Shimizu, M., Oppenheim, J. J., Fiem, S. J., Hursey, J. C., Powers, G. C., & Urba, W. J. (1993). The Effects of Treatment with Interleukin-1α on Platelet Recovery after High-Dose Carboplatin. New England Journal of Medicine, 328(11), 756-761. https://doi.org/10.1056/NEJM199303183281103