Interferon Gamma-1b Compared with Placebo in Metastatic Renal-Cell Carcinoma

Gleave, Martin; Elhilali, Mostafa; Fradet, Yves; Davis, Ian D.; Venner, Peter; Saad, Fred; Klotz, Laurence; Moore, Malcolm J.; Paton, Virginia; Bajamonde, Alex; Bell, David; Ernst, Scott; Ramsey, Ernest W.; Chin, J.; Morales, Alvaro; Martins, Heidi; Sanders, Coree

doi:10.1056/nejm199804303381804

Cited by 272 publications

(75 citation statements)

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“…[ 23 ] IFN-γ plays a central role in various anti-proliferative, anti-viral, and immunomodulatory treatments [ 24,25 ] and has also been used for many years in clinics for the treatment of chronic granulomatous disease. [ 26 ] Recombinant IFN-γ expressed in Escherichia coli has been deemed a promising antitumor agent to inhibit the growth of breast cancer cells and melanoma cells, [ 27 ] and treat hepatocellular carcinoma (HCC) and metastatic renal-cell carcinoma. [ 26 ] Our fi ndings suggest that nPCG carriers could retain the long-term effects of the induced JAK/STAT and mitochondrial pathways of all three active anticancer agents, which can regulate tumor cell survival directly through the STAT5, STAT1, and p53 associated anti-/proapoptotic cascades, resulting in the apoptosis of tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Nanogel‐Incorporated Physical and Chemical Hybrid Gels for Highly Effective Chemo–Protein Combination Therapy

et al. 2015

Adv Funct Materials

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Chemo-and protein-based therapeutics are two major modalities for the treatment of malignant tumors with drastically different therapeutic indices, toxicity, and other pharmacological properties. For intended in vivo applications, they also have distinctly different formulation challenges to be addressed separately. In this study, we attempt to overcome the formulation barriers of chemo-and protein-based therapeutics, and report the development of injectable nanogels, a class of crosslinked physical and chemical composite gels (

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Section: Introductionmentioning

confidence: 99%

Nanogel‐Incorporated Physical and Chemical Hybrid Gels for Highly Effective Chemo–Protein Combination Therapy

et al. 2015

Adv Funct Materials

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“…Recent literature provides evidence that neoplastic cells may be implantated into the skin through diagnostic or surgical procedures (Nilufer, 2011), Cutaneous manifestations of urological tumors carry a poor prognosis as they are associated with widespread visceral involvement. Retrospective studies looking at urological malilgnancies that metastasized to the skin demonstrated a median survival time of 8 months (Thomas, 2004;Gleave, 1998).…”

Section: Discussionmentioning

confidence: 99%

Renal Cell Carcinoma with Skin metastasis: A Case Report and Literature Review

Ahmad¹,

Wu²,

Tan³

2013

CCO

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Background: Renal cell carcinoma (RCC) comprises 80% of primary renal cancers in the USA. Most cases are discovered incidentally during imaging for other reasons. The majority of patients are asymptomatic upon diagnosis, yet 25% have advanced disease. The most common locations for metastasis include liver, lymph nodes, bone, and lungs. RCC presents as skin metastasis in 6% of cases. Here, we present an even rarer occurrence: of recurrent RCC presenting with cutaneous metastases following nephrectomy and immunotherapy. Case Report: A 75 year-old white male presented to his physician for a yearly exam. Routine urinalysis revealed microcytic hematuria. Ultrasound demonstrated a solid mass in the upper pole of the right kidney. CT scan of the chest revealed pulmonary nodules. Patient underwent a right radical cyto-reductive nephrectomy, biopsy of mesenteric mass, and left thoracotomy with biopsy. Final pathology revealed grade 4 RCC, clear-cell type. Patient had treatment with interferon Alpha and then interleukin-2. As third line treatment, patient was switched to bevacizumab. While on treatment, patient presented a lesion on his left back and diffuse bone pain. During physical exam, a 2 x 2.5 cm firm, immobile, subcutaneous nodule was noted. Pathological analysis revealed a tumor consistent with metastatic RCC. MRI of the brain revealed calvarial lesions with some break into the scalp soft tissue and into the epidural space. Erlotinib was added to bevacizumab. Conclusion: This case helps highlight the ubiquity of RCC metastasis. The most common locations for metastasis include lung, liver, local lymph nodes, bone, and brain. In RCC, skin lesions have been described in the literature more specifically as pustules, painful and painless nodules, and macular lesions. The differential diagnosis of a skin lesion include non-specific drug reactions, opportunistic skin infections, and metastatic disease. The definite diagnosis of metastasis is made through tissue biopsy.

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“…IFN-γ monotherapy has been studied in phase II trials, with an overall response rate of 8% [9]. In a phase III study with low dose of IFN-γ, the response rate was only 4.4% [10]. The combination of IFN-γ with IFN-α or with IFN-β has not shown superiority in terms of response rate as compared to IFN-α or IFN-β alone [9].…”

Section: Discussionmentioning

confidence: 99%

Vinblastine and Interferon-Gamma Combination with and without 13-Cis Retinoic Acid for Patients with Advanced Renal Cell Carcinoma

et al. 2002

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Background: The aim of this study is firstly to determine the response rates and toxicity of two regimens containing vinblastine (VBL) in combination with interferon-gamma (IFN-γ) in the treatment of patients with advanced renal cell carcinoma (RCC), and secondly to evaluate the additional efficacy of 13-cis retinoic acid (13-CRA) in RCC. Methods: Twenty-nine patients were included in the first trial (Trial 1) and 40 in the second one (Trial 2). The therapy given in Trial 1 consisted of VBL 0.15 mg/kg i.v. every 2 weeks and IFN-γ 100 µg s.c. 3 times weekly. In Trial 2, the therapy consisted of the same two drugs, in the same doses, plus oral 13-CRA 40 mg/day. Results: In Trial 1 there were 3 (10.3%) patients with complete response, 3 (10.3%) patients with partial response, 8 (27.6%) patients with stable disease and 15 (51.7%) patients with progressive disease. In Trial 2, there was no complete response, however, 3 (7.5%) patients had partial response. Additionally, 15 (37.5%) patients maintained stable disease and 14 (35%) patients had progressive disease. In Trial 1, the median survival was 12.56 months (95% CI, 6.8–18.3, range 0.59–42.49) and the median time to progression was 3.21 months (95% CI, 1.7–4.7, range 0.03–42.49). In Trial 2, the median survival was 9.54 months (95% CI, 5.9–13.1, range 0.43–24.1) and the median time to progression was 3.9 months (95% CI, 0.8–7, range 0.26–24.1). In Trial 1, granulocytopenia grade 3 and 4 appeared in 5 (17.2%) patients and anaemia grade 3 in 1 (3.4%) patient. In Trial 2, there were grade 3 toxicities, as granulocytopenia in 5 (12.5%) patients, anemia in 4 (10.0%) patients, stomatitis in 3 (7.5%) patients, fatigue/malaise in 3 (7.5%) patients and 1 (2.5%) had diarrhea. No toxic deaths occurred in both studies. Conclusion: The use of IFN-γ does not enhance the low response of VBL-based chemotherapy. The additional administration of 13-CRA with the combination of VBL and IFN-γ does not add to the efficacy of this combination in patients with advanced renal cell carcinoma. New active agents are needed to treat patients with this disease.

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Interferon Gamma-1b Compared with Placebo in Metastatic Renal-Cell Carcinoma

Abstract: No difference in outcome was observed in patients with metastatic renal-cell carcinoma who were treated with interferon gamma-1b as compared with placebo. These results emphasize the necessity of testing the efficacy of immunomodulators in randomized studies.

Cited by 272 publications

References 25 publications

Nanogel‐Incorporated Physical and Chemical Hybrid Gels for Highly Effective Chemo–Protein Combination Therapy

Nanogel‐Incorporated Physical and Chemical Hybrid Gels for Highly Effective Chemo–Protein Combination Therapy

Renal Cell Carcinoma with Skin metastasis: A Case Report and Literature Review

Vinblastine and Interferon-Gamma Combination with and without 13-Cis Retinoic Acid for Patients with Advanced Renal Cell Carcinoma

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