Immunotherapy of metastatic kidney cancer

Abstract

, 122 MRCC patients were treated by monthly intralymphatic injections (containing a mean of 573 IL-2 U and 26 ؋ 10 6 LAK cells) and i.m. administration of IFN and TF; 71 patients also received a 3-day cycle of monthly IL-2 inhalations with a mean of 998 daily U. MRCC cases not treated by immunotherapy (n ‫؍‬ 89) represent our historical controls. Adverse clinical side effects related to treatment were negligible. CR (n ‫؍‬ 11) and PR (n ‫؍‬ 13) were noticed in 24/122 patients. Of 24 responding patients, 17 resumed progression, whereas 7 remain in remission 11-69 months later. The overall median survival of treated patients (28 months) was 3.5-fold higher than the median survival of historical controls (7.5 months), and a Kaplan-Meier curve showed 25% survival 11 years after the beginning of immunotherapy. Apparently, the addition of IL-2 by inhalation improved survival. The present immunotherapy protocol appears to be efficacious, safe, devoid of adverse side effects, far less costly than others and able to offer a good quality of life to MRCC patients; if confirmed in a multicenter trial, it could set the basis for developing lowdose immunomodulatory treatments. © 2001 Wiley-Liss, Inc. Key words: immunotherapy; IL-2; lymphokine-activated killer cells; metastasis; transfer factor; interferon; renal cancerThe most promising systemic therapy for MRCC is immunotherapy with IL-2. 1 The original observations by Rosenberg et al., 2 using i.v. administration of high-dose rIL-2 and LAK in MRCC patients showed encouraging clinical response rates and longlasting remissions. These results have prompted many clinical trials using various administration routes: i.v. both in bolus and continuous or s.c. in combination or not with IFN and/or chemotherapeutic agents. In 1,411 MRCC patients, the overall rate of response was 20%. 3,4 Nonetheless, despite the lowering of the IL-2 dosage and the decrease of the 4% fatal outcome of the initial studies, thanks to the improved selection of patients and the clinical experience acquired, 5,6 the persistence of more often than not severely adverse clinical side effects remains the most important hindrance for the wide use of IL-2.Hence, being aware of the risk from a high IL-2 dose and of its ability to activate, at low doses, tumor mass rejection, 7-9 we attempted to develop alternative protocols. An observation made in 1 MRCC patient, in whom injection of a metastasis with IL-2 and LAK cells was followed by regression not only of the treated tumor but also of several other abdominal lymph node metastases, prompted us to further investigate the low-dose effect using the intralymphatic route. Following intratumor low-dose injections of IL-2 into infiltrating bladder cancers or lymph node metastases of MRCC patients, both the injected and the non-injected distant metastases often disappeared. 7,8 Thus, by administering very low doses of IL-2 and LAK cells into the lymphatic vessels of the foot, we observed encouraging clinical results with minimal side effects. 10,11 To boost the overall ...

Prognostic Value of Serum Lactate Dehydrogenase in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

“…Early-stage RCC patients treated with nephrectomy may have a satisfying five-year survival expectancy[2, 3]. Once metastasis occurs, molecular-targeted therapy and immunotherapy are the only ways to treat RCC due to its poor response to radiotherapy and chemotherapy[4–9]. TNM staging is typically used to predict the survival of RCC patients in clinical medicine.…”

Effect of Selective Serotonin Reuptake Inhibitors and Immunomodulator on Cytokines Levels: An Alternative Therapy for Patients with Major Depressive Disorder

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Immunotherapy of Genitourinary Malignancies

“…A third of patients present with metastatic disease and have a life expectancy of less than 12 months. The prognosis in patients with metastatic renal cell carcinoma (mRCC) is poor with approximately 1-year median survival and a 10% to 20% 2-year survival rate [2, 3]. This is largely due to the absence of effective chemotherapy agents and the limited usefulness of radiation therapy for mRCC.…”