Establishing the role of cytokine therapy in advanced renal cell carcinoma

Gore, Martin; Mulder, Pieter De

doi:10.1111/j.1464-410x.2008.07435.x

Cited by 5 publications

(2 citation statements)

References 48 publications

(51 reference statements)

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“…(1) Metastatic disease is present in around 30% of RCC patients when diagnosed, and 30-40% of patients with earlystage disease relapse with metastases following nephrectomy. Renal cell carcinoma is highly resistant to conventional cytotoxic chemotherapy and the prognoses in patients with metastatic RCC (mRCC) are poor, (2) with a median overall survival (OS) period of approximately 1 year (3) and a 5-year survival rate of <10%. (4) Immunoreactive cytokines, interferon-a (IFN-a) and interleukin-2 (IL-2) were the treatment mainstay for mRCC.…”

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confidence: 99%

Phase‐II trial of combination treatment of interferon‐α, cimetidine, cyclooxygenase‐2 inhibitor and renin‐angiotensin‐system inhibitor (I‐CCA therapy) for advanced renal cell carcinoma

Tatokoro

Fujii²,

Kawakami

et al. 2010

Cancer Science

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We have recently reported favorable responses to a combination treatment comprising cimetidine, a cyclooxygenase-2 inhibitor and a renin-angiotensin-system inhibitor in metastatic renal cell carcinoma (RCC). In view of the potential synergistic effects of these three agents and interferon-a (I-CCA therapy), we conducted a phase-II trial to examine the efficacy and toxicity of I-CCA as firstline treatment. Fifty-one patients with advanced RCC received natural interferon-a (3-6 million U thrice/week) and cimetidine (800 mg), cyclooxygenase-2 inhibitor meloxicam (10 mg), and renin-angiotensin-system inhibitor candesartan (4 mg) or perindopril (4 mg) orally daily. Memorial Sloan-Kettering Cancer Center prognostic categories were favorable, intermediate and poor in 10 (20%), 31 (61%) and 10 (20%) patients, respectively. The primary end-point was the objective response rate (ORR) and the secondary end-points included clinical benefit, progression-free survival (PFS), overall survival (OS) and safety. Median follow-up was 19 months. Complete response (CR) was observed in four patients (8%) and partial response in seven (14%), yielding an ORR of 22%. None of the four patients who achieved CR relapsed during the 16-to 81-month follow up. The ORR were 17% in the favorable-or intermediate-risk group and 40% in the poor-risk group. The other 24 patients (45%) had stable disease for at least 6 months, resulting in a clinical benefit rate of 67%. The median PFS and OS were 12 and 30 months, respectively. Grade 3/4 toxicities were never observed. The I-CCA therapy, providing favorable responses and low toxicity profiles, is worthy of further consideration as a firstline therapy for metastatic RCC. (Cancer Sci 2011; 102: 137-143) R enal cell carcinoma (RCC) is the most common renal malignancy and accounts for approximately 2% of all cancers.(1) Metastatic disease is present in around 30% of RCC patients when diagnosed, and 30-40% of patients with earlystage disease relapse with metastases following nephrectomy. Renal cell carcinoma is highly resistant to conventional cytotoxic chemotherapy and the prognoses in patients with metastatic RCC (mRCC) are poor, (2) with a median overall survival (OS) period of approximately 1 year (3) and a 5-year survival rate of <10%. Immunoreactive cytokines, interferon-a (IFN-a) and interleukin-2 (IL-2) were the treatment mainstay for mRCC.(5) Interferon-a offers a small but significant advantage in OS. (6) However, cases of complete remission (CR) by IFN-a are rare and progression-free survival (PFS) is reported to be approximately 5 months. (7,8) High-dose immunotherapy with intravenous IL-2 results in generally durable CR in approximately 6% of patients, but significant toxicities can occur with this regimen, making it applicable to a limited number of patients. Based on a better understanding of the biology and genetics of RCC, targeted agents have been developed and shown to have significant antitumor activities against RCC, resulting in dramatic paradigm shifts in the management of mRCC....

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confidence: 99%

Phase‐II trial of combination treatment of interferon‐α, cimetidine, cyclooxygenase‐2 inhibitor and renin‐angiotensin‐system inhibitor (I‐CCA therapy) for advanced renal cell carcinoma

Tatokoro

Fujii²,

Kawakami

et al. 2010

Cancer Science

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“…At present, the most widely used regimens for metastatic RCC (mRCC) are cytokine therapies, including interferon-alfa and interleukin-2, which in previous studies showed response rates of only 10–20% and resulted in debilitating adverse effects [5], [6], [7]. Studies of cytokine therapies with or without chemotherapy have shown short-term partial response rates of up to 20–35% [8], [9]. New treatments are needed to develop strategies for controlling metastatic disease and improving quality of life.…”

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confidence: 99%

Economic Evaluation of First-Line Treatments for Metastatic Renal Cell Carcinoma: A Cost-Effectiveness Analysis in A Health Resource–Limited Setting

Dong

Xu³

et al. 2012

PLoS ONE

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BackgroundTo estimate, from the perspective of the Chinese healthcare system, the economic outcomes of five different first-line strategies among patients with metastatic renal cell carcinoma (mRCC).Methods and FindingsA decision-analytic model was developed to simulate the lifetime disease course associated with renal cell carcinoma. The health and economic outcomes of five first-line strategies (interferon-alfa, interleukin-2, interleukin-2 plus interferon-alfa, sunitinib and bevacizumab plus interferon-alfa) were estimated and assessed by indirect comparison. The clinical and utility data were taken from published studies. The cost data were estimated from local charge data and current Chinese practices. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the sunitinib patient assistant program (SPAP) was evaluated via scenario analysis. The base-case analysis showed that the sunitinib strategy yielded the maximum health benefits: 2.71 life years and 1.40 quality-adjusted life-years (QALY). The marginal cost-effectiveness (cost per additional QALY) gained via the sunitinib strategy compared with the conventional strategy was $220,384 (without SPAP, interleukin-2 plus interferon-alfa and bevacizumab plus interferon-alfa were dominated) and $16,993 (with SPAP, interferon-alfa, interleukin-2 plus interferon-alfa and bevacizumab plus interferon-alfa were dominated). In general, the results were sensitive to the hazard ratio of progression-free survival. The probabilistic sensitivity analysis demonstrated that the sunitinib strategy with SPAP was the most cost-effective approach when the willingness-to-pay threshold was over $16,000.ConclusionsOur analysis suggests that traditional cytokine therapy is the cost-effective option in the Chinese healthcare setting. In some relatively developed regions, sunitinib with SPAP may be a favorable cost-effective alternative for mRCC.

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Avelumab and axitinib in the treatment of renal cell carcinoma: safety and efficacy

Leslie

Boos

Larkin

et al. 2020

Expert Review of Anticancer Therapy

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Establishing the role of cytokine therapy in advanced renal cell carcinoma

Cited by 5 publications

References 48 publications

Phase‐II trial of combination treatment of interferon‐α, cimetidine, cyclooxygenase‐2 inhibitor and renin‐angiotensin‐system inhibitor (I‐CCA therapy) for advanced renal cell carcinoma

Phase‐II trial of combination treatment of interferon‐α, cimetidine, cyclooxygenase‐2 inhibitor and renin‐angiotensin‐system inhibitor (I‐CCA therapy) for advanced renal cell carcinoma

Economic Evaluation of First-Line Treatments for Metastatic Renal Cell Carcinoma: A Cost-Effectiveness Analysis in A Health Resource–Limited Setting

Avelumab and axitinib in the treatment of renal cell carcinoma: safety and efficacy

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