Durability of Complete Responses in Patients With Metastatic Cancer Treated With High-Dose Interleukin-2
- 1 September 1998
- journal article
- clinical trial
- Published by Ovid Technologies (Wolters Kluwer Health) in Annals of Surgery
- Vol. 228 (3), 307-319
- https://doi.org/10.1097/00000658-199809000-00004
Abstract
To determine the durability of complete responses in patients with metastatic melanoma or renal cancer treated with highdose bolus interleukin-2 (IL-2) as well as the factors associated with the development of a complete response and the antigens mediating clinical responses. A consecutive series of 409 patients with either metastatic melanoma or renal cancer who were treated with high-dose bolus IL-2 in the Surgery Branch, National Cancer Institute, between September 1985 and November 1996 have been analyzed with a median potential follow-up of 7.1 years. All patients were treated with 720,000 IU/kg administered by 15-minute intravenous infusions every 8 hours for up to 5 days as clinically tolerated per cycle. Two cycles constituted a treatment course. Tumor-infiltrating lymphocytes (TIL) from melanoma patients were used to clone the genes encoding the tumor antigens responsible for clinical responsiveness. Thirty-three of 409 (8.1%) patients treated with high-dose bolus IL-2 achieved a complete response and 37 (9%) achieved a partial response. Complete regression was seen in 6.6% and 9.3% of patients with metastatic melanoma and renal cancer, respectively. Twenty-seven of these 33 completely responding patients (82%) remain in ongoing continuous complete response from 39 to more than 148 months from the onset of treatment. Tumor regressions were seen at virtually all organ sites. The absence of prior treatment with immunotherapy, the total dose of IL-2 administered, and the maximal rebound lymphocytosis after cessation of IL-2 correlated with achieving a complete response. Expression cloning techniques have identified a series of tumor antigens that are recognized by TIL grown from resected melanomas. These antigens are mainly melanoma/melanocyte differentiation antigens, although mutated intracellular proteins can also serve as antigens. Treatment with high-dose bolus IL-2 mediates complete cancer regression in approximately 8% of patients with metastatic renal cancer and melanoma. The great majority of these patients will enter durable complete regressions and appear to be cured of their metastatic cancer. Thus, immunotherapy with high-dose bolus IL-2 should be considered as initial therapy for appropriately selected patients with metastatic melanoma and renal cell cancer. Identification of the tumor antigens mediating clinical response is opening new therapeutic possibilities for cancer treatment.Keywords
This publication has 26 references indexed in Scilit:
- Utilization of an alternative open reading frame of a normal gene in generating a novel human cancer antigen.The Journal of Experimental Medicine, 1996
- Vitiligo in Patients with MelanomaJournal of Immunotherapy, 1996
- Identification of a gene encoding a melanoma tumor antigen recognized by HLA-A31-restricted tumor-infiltrating lymphocytes.The Journal of Experimental Medicine, 1995
- Treatment of Patients With Metastatic Melanoma With Autologous Tumor-Infiltrating Lymphocytes and Interleukin 2JNCI Journal of the National Cancer Institute, 1994
- Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes.The Journal of Experimental Medicine, 1994
- Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2Published by American Medical Association (AMA) ,1994
- A sharper Bonferroni procedure for multiple tests of significanceBiometrika, 1988
- High-dose recombinant interleukin 2 in the treatment of patients with disseminated cancer. Responses, treatment-related morbidity, and histologic findingsPublished by American Medical Association (AMA) ,1986
- Observations on the Systemic Administration of Autologous Lymphokine-Activated Killer Cells and Recombinant Interleukin-2 to Patients with Metastatic CancerNew England Journal of Medicine, 1985
- Choosing Between Logistic Regression and Discriminant AnalysisJournal of the American Statistical Association, 1978