Incidence Of All-grade Rash Research Articles

Treatment-related adverse effects with pazopanib, sorafenib and sunitinib in patients with advanced soft tissue sarcoma: a pooled analysis.

ObjectiveResearch efforts have investigated therapies targeting tyrosine kinase signaling pathways. We performed a pooled analysis to determine the frequency of severe adverse effects in patients with soft tissue sarcoma treated with pazopanib, sorafenib and sunitinib.Materials and methodsWe performed a comprehensive search of PubMed, Web of Science, Ovid, the Cochrane Library and Embase databases from the drugs’ inception to May 2017 to identify clinical trials. All-grade and severe adverse events (AEs; grade≥3) were analyzed.ResultsA total of 10 trials published between 2009 and 2016, including 843 patients, were eligible for analysis. We included 424 patients (three studies) who received pazopanib 800 mg daily, 353 patients (five studies) who received sorafenib 400 mg twice daily and 66 patients (two studies) who received sunitinib 37.5 mg daily. The incidence of AEs is different among the three VEGFR-tyrosine kinase inhibitors (TKIs). Pazopanib showed higher incidence of all-grade nausea, diarrhea and hypertension compared with sorafenib and sunitinib. However, patients in the sorafenib group experienced a significantly higher frequency of all-grade rash (26.1%), hand–foot syndrome (33.4%) and mucositis (38.5%). The difference was highly significant for sorafenib vs. pazopanib in the incidence of all-grade rash (odds ratio [OR] 1.649, 95% CI 1.086–2.505, P=0.023), hand–foot syndrome (OR 3.096, 95% CI 1.271–7.544, P=0.009) and mucositis (OR 4.562, 95% CI 2.132–9.609, P<0.001). Moreover, the frequency of grade ≥3 mucositis was significantly higher in the sunitinib group compared with the pazopanib or sorafenib group (7.6% vs. 1.3%, OR 6.448, 95% CI 1.499–27.731, P=0.013).ConclusionStatistically significant differences in certain common adverse effects, such as all-grade and severe AEs, were detected among pazopanib, sorafenib and sunitinib in the current study. Early and prompt management is critically needed to avoid unnecessary dose reductions and treatment-related discontinuations.

Systematic review of rash in cancer patients receiving ibrutinib and idelalisib.

e12655 Background: Ibrutinib is a BTK inhibitor approved for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) and Waldenstrom’s macroglobulinemia....

The risk of rash associated with ipilimumab in patients with cancer: A systematic review of the literature and meta-analysis

Ipilimumab is a human antibody that inhibits cytotoxic T-lymphocyte-associated antigen 4, leading to increases in T-cell activation and interleukin 2 secretion and has been approved for the treatment of advanced melanoma. Dermatologic adverse events such as rash, pruritus, and vitiligo have been reported in trials, with varying incidences. The overall incidence and risk of rash to ipilimumab is unknown. We conducted a systematic review of the literature and performed a meta-analysis to ascertain the incidence and risk of developing rash among patients receiving ipilimumab. Databases from PubMed and Web of Science from January 1998 until July 2011 and abstracts presented at the American Society of Clinical Oncology meetings from 2004 through 2011 were searched to identify relevant studies. The incidence and relative risk of rash were calculated using random effects or fixed effects model depending on the heterogeneity of included studies. A total of 1208 patients from clinical trials were included in this analysis. The overall incidence of all-grade rash was 24.3% (95% confidence interval [CI] 21.4%-27.6%), with a relative risk of 4.00 (95% CI 2.63-6.08, P < .001). The overall incidence of high-grade rash was 2.4% (95% CI 1.1%-5.1%), with a relative risk of 3.31 (95% CI 0.70-15.76, P = .13). The ability to detect rash may vary among institutions. There is a significant risk of developing rash in patients with cancer receiving ipilimumab. There was no statistically significant difference in the risk of rash based on dose or underlying tumor. Adequate monitoring and early intervention are recommended to prevent decreased quality of life and inconsistent dosing.

Risk of rash associated with lenalidomide in multiple myeloma and myelodisplastic syndrome: A systematic review of the literature and meta-analysis.

e18571 Background: Indications of lenalidomide (Len) include treatment of multiple myeloma (MM) in combination with dexamethasone (Dex) and myelodyplastic syndrome (MDS). The reported incidence and risk of rash varies widely and has been inconsistently reported in trials. Therefore, we conducted a systematic review and meta-analysis of the literature to determine the incidence and risk of developing rash. Methods: Relevant studies were identified from PubMed (1998-2011), abstracts presented at ASCO conferences (2004-2011) and the Web of Science database (1998-2011). Eligible studies were limited to prospective Phase II-III clinical trials in which patients received daily Len doses of either 10mg or 25 mg with or without 40mg of Dex. Incidence, relative risk (RR), and 95% confidence intervals (CI) were calculated using random-effects or fixed-effects models based on heterogeneity of included studies. Results: Data from a total of 1,127 patients in 15 trials were available for analysis. The overall incidence of all-grade and high-grade (grade ≥3) rash was 29.9% (95% CI: 24.8- 35.5) and 3.8% (95% CI: 2.7-5.5), respectively. Len was associated with increased risk of all-grade rash (RR=1.7, 95% CI: 1.3-2.3; P&lt;0.001) when compared to patients treated with a placebo and Dex. Risk of high-grade rash was increased (RR=3.7, 95% CI: 0.8-16.0) with a trend toward statistical significance (P=0.08). No significant difference in incidence of all-grade rash between patients receiving LEN doses of 10mg or 25mg (25.6%, 95% CI: 19.6-32.8% vs. 30.8%, 95% CI: 24.7-37.7%, respectively, p=0.28) was observed. Similarly, no difference was observed between patients receiving LEN monotherapy or in combination with Dex (31.0%, 95% CI: 26.6-43.3% and 23.8%, 95% CI: 14.9-35.8%, respectively, p=0.17). Conclusions: Patients with MM or MDS who are treated with Len are at significant risk for developing rash. The risk appears to be independent of LEN dosage or in combination with Dex. Further studies for prevention and treatment of this untoward toxicity are needed in order to maintain patient’s quality of life and minimize the need for dose modification, all of which may impact clinical outcome.

Risk of rash with nilotinib: A systematic review of the literature and meta-analysis.

9088 Background: Nilotinib is indicated for the treatment of chronic myelogenous leukemia (CML). The reported incidence and risk of rash from this medication vary widely and have been inconsistently reported in published trials. Therefore we conducted a systematic review and meta-analysis of the literature to determine the incidence and risk of developing rash. Methods: Relevant studies were identified from the PubMed database (1998-2012), abstracts presented at ASCO and ASH Conferences (2004-2011) and Web of Science database (1998-2012). Eligible studies were limited to prospective Phase II-III clinical trials in which patients received nilotinib at doses of either 300 mg or 400 mg twice daily. Incidence, relative risk (RR), and 95% confidence intervals (CI) were calculated using random-effects or fixed-effects models based on heterogeneity of included studies. Results: Data from a total of 3,186 patients receiving nilotinib in 16 clinical trials were available for analysis. The overall incidence of all-grade and high-grade (grade ≥3) rash were 33.1% (95% CI: 27.7-39.1) and 2.6% (95% CI: 2.1-3.4), respectively. Incidence of all-grade rash for patients with CML, gastrointestinal stromal tumor (GIST) and systemic mastocytosis were 33.2% (95% CI: 27.2-39.9), 25.7% (95% CI: 14.0-42.5) and 25.0% (95% CI: 15.7-37.4), respectively. Nilotinib was associated with increased risk of all-grade rash (RR=2.891, 95% CI: 2.079-4.020; P&lt;0.001) when compared to patients treated with imatinib. Risk of high-grade rash was increased compared to imatinib (RR=1.823, 95% CI: 0.670-4.957), but this was not statistically significant (P=0.24). Conclusions: Patients with hematologic malignancies and GIST who are treated with nilotinib are at significant risk for developing a rash. Further studies for characterization, prevention and treatment of this untoward toxicity are needed in order to maintain patients’ quality of life and minimize the need for dose modification, which may impact clinical outcome.

The risk of skin rash and stomatitis with the mammalian target of rapamycin inhibitor temsirolimus: A systematic review of the literature and meta-analysis

ObjectiveWe conducted a systematic review of the literature and performed a meta-analysis to determine the risk of developing skin rash and stomatitis among patients receiving temsirolimus. MethodsDatabases from PubMed and Web of Science from January, 1998 until June, 2011 and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through 2011 were searched to identify relevant studies. The incidence and relative risk (RR) of skin rash and stomatitis were calculated using random-effects or fixed-effects model depending on the heterogeneity of included studies. ResultsA total of 779 patients from 10 clinical trials were included in this analysis. The overall incidence of all-grade rash was 45.8% (95% confidence interval (CI): 35.6–56.3%), with a RR of 7.6 (95%CI: 4.4–13.3; p<0.001). The overall incidence of high-grade rash was 3.3% (95%CI: 1.9–5.6%), with a RR of 13.70 (95%CI: 0.82–227.50, p=0.07). The overall incidence of all-grade stomatitis was 44.3% (CI: 32.1–57.1%), with a RR of 11.10, 95%CI: 5.60–22.00; p<0.001). The overall incidence of high-grade stomatitis was 3.2% (95%CI: 1.9–5.4%), with a RR of 13.2 (95%CI: 0.80–218.50, p=0.07). ConclusionThere is a significant risk of developing skin rash and stomatitis in cancer patients receiving temsirolimus. The risk is independent of underlying tumour. Adequate monitoring and early intervention are recommended to prevent debilitating toxicity and suboptimal dosing.

Risk of rash and stomatitis with temsirolimus, a mammalian target of rapamycin (mTOR) inhibitor: A meta-analysis.

e15031 Background: Temsirolimus, an mTOR inhibitor, is approved for treatment of advanced renal cell carcinoma (RCC). Maculopapular/acneiform rash and stomatitis are the most common mucocutaneous toxicities. We systematically investigated the overall incidence and risk of rash and stomatitis in patients receiving temsirolimus. Methods: Relevant studies were identified from PubMed database (1999-2010) and abstracts presented at the American Society of Clinical Oncology Conferences between 2004 and 2010. A citation database Web of Science was searched to ensure that no relevant studies were missed. Eligible studies were limited to prospective Phase II-III clinical trials and expanded-access programs in which cancer patients received temsirolimus 25 mg weekly as a single agent. Incidence, relative risk (RR), and 95% confidence intervals were calculated using random-effects or fixed-effects models based on heterogeneity of included studies. Results: A total of 579 patients from 10 clinical trials were available for analysis. The overall incidence of all-grade and high-grade (grade ≥3) rash was 46.7% (95% CI: 37.5- 56.1) and 3.2% (95% CI: 1.9-5.3), respectively. The overall incidence of all-grade and high-grade stomatitis was 44.3 % (CI: 32.1- 57.1) and 3.2% (95% CI: 1.9-5.4). Temsirolimus was associated with significantly increased risk of all-grade rash and all-grade stomatitis (RR=7.8, 95% CI: 4.5-13.6; P<0.001 and RR=11.1, 95% CI: 5.6-22.0; P<0.001) when compared to patients treated with IFN. The risk of high-grade rash and stomatitis was increased (RR=13.2, 95% CI: 0.8-219.8 and RR=13.2, 95% CI: 0.8-218.5) with a trend reaching statistical significance (P=0.07). No significant difference in incidence of all-grade rash between RCC and non-RCC patients was noted (42.6%, 95% CI: 18.4-70.9% vs. 47.6%, 95% CI: 39.2-56.2%, respectively, p=0.75). Similarly, no difference in all-grade stomatitis was observed (36.5%, 95% CI: 14.9-65.4% and 47.8%, 95% CI: 35.8-60.1%, respectively, p=0.47). Conclusions: Cancer patients treated with temsirolimus are at significant risk for developing skin rash and stomatitis. Further studies for prevention and treatment of these untoward toxicities are needed.