Oxaliplatin, 5-Fluorouracil, and Folinic Acid (Folfox) in Patients With Metastatic Renal Cell Carcinoma

Chaouche, M.; Pasturaud, Alain-louis; Kamioner, D.; Grandjean, Michel; Franiatte, J; Tourani, Jean-Marc

doi:10.1097/00000421-200006000-00016

Cited by 9 publications

(4 citation statements)

References 3 publications

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“…Phase II trials conducted with new agents such as taxanes or gemcitabine were ineffective as well [6, 7]. The negative results of our study confirm those of a recent pilot study in which 14 patients previously treated by cytokines failed to respond to the FOLFOX-4 regimen [8]. These two trials indicate that further studies with oxaliplatin are not profitable in this disease.…”

Section: Discussionsupporting

confidence: 66%

A Phase II Study with 5-Fluorouracil, Folinic Acid and Oxaliplatin (FOLFOX-4 Regimen) in Patients with Metastatic Renal Cell Carcinoma

Bennouna¹,

Delva²,

Gómez

et al. 2002

Oncology

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Purpose: To investigate the efficacy and safety of the FOLFOX-4 regimen for patients with metastatic renal cell carcinoma (MRCC). Patients and Methods: Fifty-nine patients (median age 59 years) pre-treated or not by cytokines (29 vs. 30) received the FOLFOX-4 regimen every 2 weeks. Results: Three minor responses, and no complete or partial responses were obtained. The median progression-free survival was 3 months (95% CI: 2.6–3.4), the median survival 10.6 months (95% CI: 8.7–12.4), with no difference between pre-treated patients and others. Treatment was well tolerated. Conclusion: The FOLFOX-4 regimen is ineffective in patients with MRCC. We believe that oxaliplatin should no longer be explored in renal carcinoma.

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Section: Discussionsupporting

confidence: 66%

A Phase II Study with 5-Fluorouracil, Folinic Acid and Oxaliplatin (FOLFOX-4 Regimen) in Patients with Metastatic Renal Cell Carcinoma

Bennouna¹,

Delva²,

Gómez

et al. 2002

Oncology

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“…Oxaliplatin is a platinum-based chemotherapy and is typically used in combination therapies for the treatment of colorectal cancer. Early clinical trials showed that oxaliplatin is ineffective against advanced RCC (3,4). One of the major mechanisms of platinum resistance in this cancer type is inadequate amounts of platinum reaching the target DNA (5).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic activation of the drug transporter OCT2 sensitizes renal cell carcinoma to oxaliplatin

Liu

Zheng

et al. 2016

Sci. Transl. Med.

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Renal cell carcinoma (RCC) is known for its multidrug resistance. Using data obtained from the cancer transcriptome database Oncomine and the proteome database The Human Protein Atlas, we identified the repression of organic cation transporter OCT2 as a potential factor contributing to oxaliplatin resistance in RCC. By analyzing OCT2 expression in collected patient tissues and commercial tissue microarray specimens, we demonstrated OCT2 repression in RCC at both transcription and protein levels. Epigenetic analysis revealed that the repressed OCT2 promoter in RCC is characterized by hypermethylated CpG islands and the absence of H3K4 methylation. Further mechanistic studies showed that DNA hypermethylation blocked MYC activation of OCT2 by disrupting its interaction with the E-Box motif, which prevented MYC from recruiting MLL1 to catalyze H3K4me3 at the OCT2 promoter and resulted in repressed OCT2 transcription. Targeting this mechanism, we designed a sequential combination therapy and demonstrated that epigenetic activation of OCT2 by decitabine sensitizes RCC cells to oxaliplatin both in vitro and in xenografts. Our study highlights the potential of translating "omics" data into the development of targeted therapies.

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“…In fact, no objective responses were observed in either a small pilot study of the FOLFOX-4 (5-FU, leucovorin, and L-OHP) regimen 26 or a larger (n ϭ 59) Phase II study of the same regimen. 27 In conclusion, our results suggest a certain level of activity, with an acceptable toxicity profile, for the FIGURE 2.…”

Section: Discussionmentioning

confidence: 99%

Gemcitabine and oxaliplatin in the treatment of patients with immunotherapy‐resistant advanced renal cell carcinoma

Porta

Zimatore

Imarisio

et al. 2004

Cancer

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BACKGROUNDCurrently, there is no standard treatment for patients with advanced renal cell carcinoma (RCC) who do not experience a response to first‐line immunotherapy. In the current Phase II study, the authors explored the antitumor activity of a combination of gemcitabine and oxaliplatin (L‐OHP) in this setting.METHODSForty‐two patients with RCC who had progressive disease following immunotherapy received gemcitabine (1000 mg/m2 intravenously on Days 1 and 8 every 21 days) and L‐OHP (90 mg/m2 intravenously on Day 1 every 21 days) for a minimum of 2 cycles before responses were evaluated. Responses to treatment and toxicity were recorded according to the Response Evaluation Criteria in Solid Tumors and the National Cancer Institute Common Toxicity Criteria, respectively.RESULTSNo complete responses were recorded; however, 6 patients experienced a partial response (14.28%; 95% confidence interval, 5.43–28.5%), 11 patients (26.19%) had temporary stable disease as a best response, and the remaining 25 patients (59.52%) experienced progression despite receiving treatment. The median time to disease progression was 2.5 months (mean, 3.86 months; range, 1.5–11.0 months), whereas the median overall survival was 9.5 months (mean, 10.46 months; range, 4.0–22.5 months). With regard to toxicity, treatment generally was well tolerated, with only one episode of Grade 4 toxicity and expected episodes of Grade 3 toxicity, including myelosuppression and neuropathy.CONCLUSIONSThe current results suggest that the combination of gemcitabine and L‐OHP possesses a certain level of activity and an acceptable toxicity profile in patients with immunotherapy‐resistant advanced RCC. Cancer 2004. © 2004 American Cancer Society.

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Oxaliplatin, 5-Fluorouracil, and Folinic Acid (Folfox) in Patients With Metastatic Renal Cell Carcinoma

Cited by 9 publications

References 3 publications

A Phase II Study with 5-Fluorouracil, Folinic Acid and Oxaliplatin (FOLFOX-4 Regimen) in Patients with Metastatic Renal Cell Carcinoma

A Phase II Study with 5-Fluorouracil, Folinic Acid and Oxaliplatin (FOLFOX-4 Regimen) in Patients with Metastatic Renal Cell Carcinoma

Epigenetic activation of the drug transporter OCT2 sensitizes renal cell carcinoma to oxaliplatin

Gemcitabine and oxaliplatin in the treatment of patients with immunotherapy‐resistant advanced renal cell carcinoma

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