Immunotherapy of Metastatic Renal Cell Cancer

Fishman, Mayer; Seigne, John D.

doi:10.1177/107327480200900404

Cited by 40 publications

(35 citation statements)

References 80 publications

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“…In an attempt to reproduce or accentuate this response, various immunotherapeutic strategies have been used, including nonspecific stimulators of the immune system, specific antitumor immunotherapy, adoptive immunotherapy, the induction of a graft-versus-tumor response via allogeneic hematopoietic stem cell transplantation, and the administration of partially purified or recombinant cytokines (3)(4)(5)(6). Although many such therapies display antitumor activity, research during the past 2 decades has tended to focus on various cytokines of which the protein structure and biological properties are more clearly defined.…”

Section: Introductionmentioning

confidence: 99%

Update on the Role of Interleukin 2 and Other Cytokines in the Treatment of Patients with Stage IV Renal Carcinoma

Atkins

Regan

McDermott

2004

Clinical Cancer Research

132

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Immunoreactive cytokines have been the mainstay of treatment of renal cancer for the past 15 years. Most research has focused on interferon alpha (IFN-␣) and interleukin 2 (IL-2). IFN-␣ has been shown in Phase III studies to produce a modest survival advantage over inactive or non-IFN-containing regimens. Its general tolerability, multiple proposed mechanisms of action, and familiarity have prompted IFN-␣ to be studied in combination with a variety of agents with potential activity against renal cell carcinoma. These various studies may justify an increased role for IFN-␣ in the treatment of renal cancer in the foreseeable future. High-dose bolus IL-2 remains the only treatment for stage IV renal cancer approved by the United States Food and Drug Administration. Food and Drug Administration approval was granted in 1992 based on the ability of this agent to produce durable complete responses in a small number of patients. Unfortunately, the toxicity, expense, and restricted accessibility of high-dose IL-2 make it a poor standard. Regimens involving lower doses of IL-2 either alone or in combination with IFN-␣ have generally produced fewer tumor regressions of less overall quality. Recent efforts have focused on trying to identify factors predictive of response to IL-2 therapy so that this treatment could be limited to those most likely to benefit.

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Section: Introductionmentioning

confidence: 99%

Update on the Role of Interleukin 2 and Other Cytokines in the Treatment of Patients with Stage IV Renal Carcinoma

Atkins

Regan

McDermott

2004

Clinical Cancer Research

132

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“…29 However, reviews of IL-2 activity have reported a 3-8% complete response (CR) rate not observed with IFN-␣ treatment. 17,24 Therefore, to optimize the response to IL-2 treatment, several agents, including IFN-␣, have been combined with IL-2. Some benefit has been noted with IL-2 combination regimens to date, although mortality rates for patients with MRCC remain high.…”

mentioning

confidence: 99%

“…12 Metastatic RCC (MRCC) is comparatively more resistant to cytotoxic therapy and radiotherapy than other cancers. [13][14][15][16][17][18][19][20][21][22] Reviews of more than 100 trials have failed to associate a single agent with consistent levels of antitumor activity, 13,22 and to our knowledge no single-agent or combination regimen is currently accepted as the standard of care. 6,13 To our knowledge, the most effective treatment currently available is immunotherapy with interferon-␣ (IFN-␣) or interleukin-2 (IL-2), which produce an objective response in 6 -21% of patients.…”

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confidence: 99%

Phase I/II study of thalidomide in combination with interleukin‐2 in patients with metastatic renal cell carcinoma

Amato

Morgan

Rawat

2006

Cancer

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BACKGROUNDThe purpose of the study was to determine, in a Phase I/II study, the efficacy and safety profile of thalidomide with interleukin‐2 (IL‐2) in patients with metastatic renal cell carcinoma (MRCC).METHODSFifteen patients (8 of whom were previously treated) enrolled in Phase I were treated with escalating doses of oral thalidomide (200–600 mg) and a fixed dose of IL‐2 (7 mIU/m2) by subcutaneous injection. A course was 6 weeks, with the exception of Course 1, which was 7 weeks. Thirty‐seven Phase II patients who had not received prior chemotherapy or immunotherapy for renal cell carcinoma (RCC) received an initial thalidomide dose of 200 mg at Week 0, which was escalated to 400 mg after 48 hours. Subcutaneous IL‐2 was administered at the same fixed daily dose used in Phase I.RESULTSFifty‐one of 52 Phase I/II patients were evaluable. Twenty‐seven patients (52%) experienced disease control, including 4 (8%) complete responses, 15 (29%) partial responses, and 8 (15%) cases of stable disease. Disease progression was observed in 24 patients (47%). Survival in the 2 phases ranged from 4 weeks to 45.2+ months. At the time of last follow‐up, 2 of 51 patients (4%) remained on maintenance thalidomide therapy and continue to be followed. Three of the 51 patients with CRs (6%) ceased thalidomide therapy at 23–25 months and have maintained their responses to date. One complete responder was lost to follow‐up. As of January 2005, 14 of 51 patients (27%) remained alive. Toxicities were mild to moderate, including Grade 1 to 2 somnolence, constipation, neuropathy, rash, flu‐like symptoms, fluid retention, hypotension, and hypothyroidism (according to version 2.0 of National Cancer Institute Common Toxicity Criteria). In addition, two patients experienced deep venous thrombosis.CONCLUSIONSThalidomide in combination with IL‐2 is tolerable and can produce durable, active responses in patients with MRCC. To evaluate the merits of thalidomide as a valuable agent against MRCC and to more fully determine the efficacy of thalidomide/IL‐2 combination therapy, the scrutiny of Phase III testing is required. Further development of thalidomide/IL‐2 combination therapy will be the focus of this group. Cancer 2006. © 2006 American Cancer Society.

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“…To date, despite reports showing the effects of various cytokines on RCC, extensive clinical evaluation has been performed focusing on interferon-a (IFN-a) and interleukin-2 (IL-2). 2 However, several problems associated with the use of these agents were suggested, including limited antitumor activity, short response duration, high cost, and severe toxicity. 1,2 Because of preclinical data suggesting synergistic effects of IFN-a and IL-2, 3,4 several recent studies have focused on combined treatment with IFN-a and IL-2 for advanced RCC.…”

Section: Introductionmentioning

confidence: 99%

Clinical outcome of combined immunotherapy with low-dose interleukin-2 and interferon-α for Japanese patients with metastatic renal cell carcinoma who had undergone radical nephrectomy: a preliminary report

et al. 2005

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Our preliminary experience suggests that long-term, repeated treatment with IFN-alpha and low-dose IL-2 is feasible in Japanese patients with metastatic RCC who have undergone radical nephrectomy. Although it will be necessary to accumulate data from a larger number of patients with a longer follow-up period, the combined immunotherapy tested in this study may become the preferred therapy for Japanese patients with metastatic RCC.

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Immunotherapy of Metastatic Renal Cell Cancer

Cited by 40 publications

References 80 publications

Update on the Role of Interleukin 2 and Other Cytokines in the Treatment of Patients with Stage IV Renal Carcinoma

Update on the Role of Interleukin 2 and Other Cytokines in the Treatment of Patients with Stage IV Renal Carcinoma

Phase I/II study of thalidomide in combination with interleukin‐2 in patients with metastatic renal cell carcinoma

Clinical outcome of combined immunotherapy with low-dose interleukin-2 and interferon-α for Japanese patients with metastatic renal cell carcinoma who had undergone radical nephrectomy: a preliminary report

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