Hand-Foot Skin Reaction is Associated with the Clinical Outcome in Patients with Metastatic Renal Cell Carcinoma Treated with Sorafenib

BACKGROUND Hand-foot skin reaction (HFSR) is a serious side effect induced by multiple-tyrosine kinase inhibitors (TKIs). HFSR can cause treatment interruption or decreased dosing. HFSR also markedly decreases quality of life and is associated with the therapeutic efficacy of multiple-TKIs. Therefore, the management and prevention of HFSR is an important issue; however, an effective method for its prevention has not been established. Specific ascorbic acid derivatives can reverse multiple-TKI-induced keratinocyte growth and pathological changes in vitro. OBJECTIVE This study was designed to evaluate the safety of bis-glyceryl ascorbate (Amitose DGA), a novel, hydrosoluble, and moisturizing ascorbic acid derivative, in patients with renal cell carcinoma (RCC) receiving sunitinib therapy. This study was also designed to evaluate Amitose DGA’s preventive efficacy for sunitinib-induced HFSR. METHODS This is a Phase I/II, single-center, uncontrolled, single-arm, open-label trial. We will recruit a total of 30 patients with RCC receiving sunitinib therapy, with a 2-week-on and 1-week-off schedule. The participants will apply Amitose DGA-containing cream over both palmar and plantar surfaces within two treatment cycles (ie, 6 weeks) of sunitinib in combination with a general moisturizing agent, in addition to standard-of-care processes. Safety assessments will include dermatological abnormalities, clinical laboratory tests, and incidence of adverse events. Efficacy assessments will include development of HFSR and therapeutic outcomes associated with sunitinib. RESULTS Recruitment to the study began in August 2017 and is ongoing in Japan. To date, 21 subjects have been recruited. Study completion is expected in 2021. CONCLUSIONS This is the first clinical study of Amitose DGA-containing cream in patients with RCC who are receiving sunitinib therapy. The single-center, single-arm, open-label design was selected to maximize subject exposure and increase the likelihood of achieving our study endpoints. The results will provide valuable and preliminary evidence of the effects of Amitose DGA-containing cream on HFSR. CLINICALTRIAL UMIN Clinical Trials Registry UMIN000027209; https://upload.umin.ac.jp/cgi-open-bin/ctr /ctr_view.cgi?recptno=R000031174 INTERNATIONAL REGISTERED REPOR DERR1-10.2196/14636

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Randomized trial assessing impact of probiotic supplementation on gut microbiome and clinical outcome from targeted therapy in metastatic renal cell carcinoma

Cancer Medicine ◽

10.1002/cam4.3569 ◽

2020 ◽

Author(s):

Nazli Dizman ◽

JoAnn Hsu ◽

Paulo G. Bergerot ◽

John D. Gillece ◽

Megan Folkerts ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Targeted Therapy ◽

Clinical Outcome ◽

Randomized Trial ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Gut Microbiome ◽

Renal Cell ◽

Probiotic Supplementation

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Development of de novo psoriasis during nivolumab therapy for metastatic renal cell carcinoma: immunohistochemical analyses and clinical outcome

Apmis ◽

10.1111/apm.12658 ◽

2017 ◽

Vol 125 (3) ◽

pp. 259-263 ◽

Cited By ~ 10

Author(s):

Juan Ruiz-Bañobre ◽

Ihab Abdulkader ◽

Urbano Anido ◽

Luis León ◽

Rafael López-López ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Clinical Outcome ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

De Novo ◽

Immunohistochemical Analyses

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Targeted therapy and hand–foot skin reaction in advanced renal cell carcinoma

Expert Opinion on Drug Safety ◽

10.1517/14740331003596349 ◽

2010 ◽

Vol 9 (3) ◽

pp. 459-470 ◽

Cited By ~ 12

Author(s):

Chih-Hsun Yang ◽

Cheng-Keng Chuang ◽

Jia-Juan Hsieh ◽

John Wen-Cheng Chang

Keyword(s):

Renal Cell Carcinoma ◽

Targeted Therapy ◽

Cell Carcinoma ◽

Skin Reaction ◽

Renal Cell ◽

Advanced Renal Cell Carcinoma ◽

Hand Foot Skin Reaction

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A randomized multicenter phase II trial on efficacy of a hydrocolloid dressing containing ceramide with a low-friction external surface for hand-foot skin reaction caused by sorafenib in patients with renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.9623 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 9623-9623

Author(s):

Nobuo Shinohara ◽

Norio Nonomura ◽

Go Kimura ◽

Masatoshi Eto ◽

Hironobu Minami ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Skin Reaction ◽

Renal Cell ◽

External Surface ◽

Low Friction ◽

Hydrocolloid Dressing ◽

Dermatologic Toxicity ◽

Hand Foot Skin Reaction ◽

Soles Of The Feet

9623 Background: Hand-foot skin reaction (HFSR) is the most clinically significant and dose-limiting dermatologic toxicity in metastatic renal cell carcinoma (mRCC) patients who receive sorafenib (SOR). At present, evidence-based management strategy is not completely established. Since HFSR may be attributed to keratinous disorders of the skin and tends to develop in areas on the soles of the feet subject to strong pressure, a hydrocolloid dressing containing ceramide (a protective dressing against pressure ulcer) may prevent the development and worsening of HFSR. The purpose of the study is to investigate the usefulness of this material for HFSR on the soles of the feet in mRCC patients treated with SOR. Methods: Patients with grade 1 HFSR on the soles of the feet were randomly assigned 1:1 to receive a hydrocolloid dressing containing ceramide (Arm A) or 10% urea cream (Arm B). The detailed protocol of this study was presented in ASCO 2011 (Trial in Progress; TPS 233). A hydrocolloid dressing containing ceramide was applied to affected sites on the soles of the feet, but not to the hands. The primary endpoint was the incidence of Grade 2 or 3 HFSR on the soles of the feet in the first 4 weeks. Results: Thirty-three patients were evaluated; 17 patients in Arm A and 16 patients in Arm B. There were no significant differences in baseline characteristics between two arms. Over the 4 weeks period of this study, the incidence of Grade 2 or 3 HFSR on the soles of the feet was significantly lower in Arm A than Arm B; 5 (29%) patients in Arm A versus 11 (69%) in Arm B, p=0.03. On the other hand, the incidence of HFSR on the hands was similar between two arms. The median time to Grade 2 or 3 HFSR on the soles of the feet was significant longer in Arm A compared with Arm B; not reach (95%CI 13-28+) in Arm A versus 22 days (95%CI 15-27), p=0.03. Regarding the pain levels on the soles, Arm A was superior to Arm B (p=0.05). Conclusions: These results indicate that a hydrocolloid dressing containing ceramide with a low-friction external surface is effective in preventing the worsening of HFSR caused by SOR in mRCC patients. Clinical trial information: UMIN000002016.

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Clinical outcome of patients with metastatic renal cell carcinoma who interrupted VEGFR-TKI after achieving stable disease or better response.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.459 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 459-459

Author(s):

Dong Hoe Koo ◽

Inkeun Park ◽

Jae-Lyun Lee ◽

Jin-Hee Ahn ◽

Dae Ho Lee ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Clinical Outcome ◽

Cell Carcinoma ◽

Disease Progression ◽

Metastatic Renal Cell Carcinoma ◽

Stable Disease ◽

Renal Cell ◽

Progression Free Survival ◽

Free Survival

459 Background: The purpose of the this study is to evaluate the clinical outcome of VEGFR-TKIs interruption in patients with metastatic renal cell carcinoma (mRCC) after achieving stable disease (SD) or better response. Methods: A retrospective analysis of medical records and imaging studies was performed on all patients with mRCC treated with VEGFR-TKIs between January 2008 and July 2014 (n=505). Patients who achieved SD or better response under VEGFR-TKI and later discontinued VEGFR-TKIs for any reason with the exception of disease progression were included in the analysis. Outcomes analyzed were progression free survival (PFS) after VEGFR-TKIs discontinuation, patterns of disease progression, time to subsequent therapy (TST), response to VEGFR-TKI resumption, and time to treatment failure (TTF) after TKI resumption. Results: We identified 32 patients (sunitinib=20, sorafenib=7, and pazopanib=5). The responses to VEGFR-TKIs were CR (n=4), PR (n=11), SD (n=15), and controlled but non-measurable (n=2). Median time to interruption from the initiation of VEGFR-TKI therapy was 16.6 months (95% CI, 12.8-20.3). The main causes of VEGFR-TKI interruption was toxicity (n=19, 59.4%), will to have treatment holiday (n=7, 21.8%), patient’s refusal (n=3, 9.4%), and others (n=3, 9.4%). At the time of analysis, 16 patients had disease progression and 1 patient was dead. With a median follow-up duration of 56.6 months (range, 12.6-167.4), median PFS from VEGFR-TKI interruption was 23.8 months (95% CI, 12.5-35.0), and the median TST was 26.2 months (95% CI, 15.9-36.6). The progression was observed in pre-existing lesions in 7 patients (43.7%) or new lesions developed in 9 (56.3%). Among 11 patients who received VEGFR-TKI resumption, 2 patients (18.2%) achieved a PR and the stable disease was observed in 9 (81.8%) with a median TTF of VEGFR-TKI resumption of 6.2 months (95% CI, 4.0-8.4). Conclusions: In patients with mRCC controlled with VEGFR-TKIs, VEGFR-TKI could be interrupted at least temporarily when clinically warranted.

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