Severity Of Skin Toxicity Research Articles

Possibilities of remote monitoring to manage skin toxicity in oncology patients

Purpose. Analysis of the effectiveness of remote monitoring in the management of skin toxicity in oncology patients.Materials and methods. A comparative study of 2 cohorts of oncology patients with skin toxicity receiving supportive care through remote monitoring using the PSP “Healthy Skin” and outpatient consultations. Nonparametric statistical methods were used with a significance level of p<0.05.Results. A comparative analysis of 150 patients divided into 2 equal groups showed the effectiveness of using the remote monitoring (group 1) in the form of a reliable decrease in median BSA (%) by 67 %, 5D itching scale by 65 %, DLQI by 70 % compared to 10 %, 22 %, 20 % in group 2, respectively, over 4 weeks of the study. In group 2, deterioration of the skin condition was noted in 13.3 % of patients, 9 % of patients underwent a reduction in the dose of the anticancer therapy, 5 % had a break, while in group 1 such episodes were not noted due to the stability of the condition. Positive dynamics in the form of a decrease in the severity of skin toxicity was noted in 48 % of cases in group 1 and in 10 % of cases in group 2. An assessment of patient satisfaction with the use of the application (B 2C (business-to-consumer) analysis) revealed satisfaction in 91.4 % of respondents.Conclusion. The availability and effectiveness of the use of the PSP «Healthy Skin» will ensure timely supportive care, significantly reduce the severity of skin toxicity and improve the quality of life in oncology patients.

A Preliminary Study Examining the Correlation between EGFRI Treatment, Clinic Dermatoscopy Features, and Serum Levels of Anti-Alpha-Galactosyl IgE in Colorectal Cancer Patients

The introduction of molecularly targeted therapies, particularly the epidermal growth factor receptor inhibitors (EGFRIs), has had a positive impact by increasing the life expectancy of patients with advanced colorectal cancer (CRC). The most used anti-EGFRIs monoclonal antagonist, Cetuximab, induces skin responses in most patients, leading to a reduction of dosages or even therapy discontinuation, all with devastating effects. Our study aimed to assess the predictive role and the possible correlations of clinical features, imaging aspects (dermatoscopy), and laboratory tests (anti-alpha-galactosyl IgE levels) for early detection of Cetuximab skin toxicity in patients with metastatic CRC. The association of IgE antibodies against goat alpha-1,3-galactose serum levels with various degrees of skin toxicity encountered during the oncologic treatment resulted in higher concentrations in patients with pruritus and hair changes. Incorporating dermatoscopy into the routine dermatological consultation allowed us to perform a severity assessment, dynamically record, and identify even the erupting lesions previously invisible to classical examination. Hence, we were enabled to generate a broad report and to classify various degrees of skin toxicity severity linked to Cetuximab treatment in 19 patients with metastatic CRC. Detecting the emergent lesions and initiating dermatological treatment in the early stages decreased the severity of skin toxicity. As a result, the duration of the antibiotic treatment was much shorter, and the risk of dose reduction or interruption of the cancer treatment was diminished. In conclusion, we emphasize the need for a regular dermatological examination with dermatoscopy of CRC patients undergoing Cetuximab treatment. Skin toxicity is a significant concern for these patients, and healthcare providers should be vigilant in monitoring and managing this side effect in order to optimize patient care. The correlation between anti-alpha-Gal IgE levels and Cetuximab-induced skin toxicities is an emerging area. More extensive studies need to be published in order to establish this relationship directly.

Intermittent or continuous panitumumab plus FOLFIRI (FOLFIRI/PANI) for first-line treatment of patients (pts) with RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC): An update of survival/toxicity and preliminary results of genomic alterations from IMPROVE study.

3571 Background: IMPROVE is a randomized, non-comparative multicenter, phase 2 study which evaluated continuous, until progressive disease (PD), or intermittent FOLFIRI/PANI, in pts with unresectable and previously untreated RAS/BRAF wt mCRC. In the intermittent schedule 8 cycles were followed by a treatment free interval lasting until PD when another 8 cycles were restarted, continuing this strategy until PD occurred on treatment. Primary endpoints was progression-free survival on treatment (PFSOT) at 1 year. In a previous analysis the primary endpoint of the study was met and a reduced skin toxicity was observed in the intermittent arm. Here we report an updated analysis. Methods: Updated analysis includes PFSOT and toxicity with 9 months (mo) of additional follow-up. Moreover we report overall survival (OS), skin toxicity burden (STB) score and preliminary data on genomic alterations (GAs) in 46 pts with PD. STB score, incorporating both the frequency and the severity of skin toxicity, was obtained by summing all grades that the pts experienced across all treatment cycles. GAs were performed by NGS on circulating tumor DNA (ctDNA) from paired plasma samples (baseline and progression), focusing specifically on RAS, BRAF and PI3K mutations. Results: Pts received FOLFIRI/PANI continuously (arm A, 69 pts) or intermittently (arm B, 67 pts). Median number of FOLFIRI/PANI cycles administered per pt were (arm A/B) 13/16. In arm B, after induction treatment, 24/53 pts (45%) without PD had ≥ 2 rounds of 8 FOLFIRI/PANI cycles. ORR (arm A/B) was 63/57%. At a median follow-up of 28 mo (IQR: 21-37), median PFSOT (77% of events) was 11.4 mo (95% CI: 9.1-13.7) in arm A, and 18.1 mo (95% CI: 6.8-29.3) in arm B. Median PFSOT in left sided tumors was 11.7 mo (95% CI: 9.1-14.3) in arm A and 23.9 mo (95% CI: 15.0-32.9) in arm B, compared with 10.7 mo (95% CI: 7.3-14.1) and 7.9 mo (95% CI: 5.7-10.1) in right sided pts, respectively. OS (46% of events) was 31.0 mo (95% CI: 24.7-37.2) in arm A and 32.2 mo (95% CI: 23.6-40.8) in arm B. Main grade ≥ 3 toxicities were (arm A/B): skin 30/18%, neutropenia 25/24%; diarrhea 13/15%. Median STB score was 0.77/cycle (IQR: 0.20-1.06) in arm A and 0.36/cycle (IQR: 0-0.77) in arm B. GAs in baseline ctDNA were evidenced in 12/46 (26%) pts, persisting to PD in all but one pt. Among the 34 pts without baseline GAs, only 8 (23%) developed ≥ 1 acquired GAs (Acq-GAs) to PD. Conclusions: Updated analyses confirmed that intermittent FOLFIRI/PANI strategy produces a long PFSOT and a reduced skin severe and skin burden toxicity without any detrimental effect on OS. Preliminary data on Acq-GAs suggest that classical mutations associated with anti-EGFR resistance are infrequent with up-front use of anti-EGFR/chemotherapy. Clinical trial information: NCT04425239 .

TARC/CCL17 Expression Is Associated with CD8+ T Cell Recruitment in Abacavir-Induced Skin Hypersensitivity in HLA-Transgenic Mice.

Abacavir (ABC)-induced hypersensitivity (AHS) is strongly associated with human leukocyte antigen (HLA)-B*57 : 01 expression. Previous studies have demonstrated the feasibility of applying the HLA-transgenic mouse model in this context. ABC-induced adverse reactions were observed in HLA-B*57 : 01 transgenic (B*57 : 01-Tg) mice. Moreover, regulating immune tolerance could result in severe AHS that mimics symptoms observed in the clinical setting, which were modeled in CD4+ T cell-depleted programmed death-1 receptor (PD-1) knockout B*57 : 01-Tg (B*57 : 01-Tg/PD-1-/-) mice. Here, we aimed to examine whether thymus and activation-regulated chemokine (TARC)/CCL17 level can be used as a biomarker for AHS. Serum TARC levels increased in HLA-B*57 : 01-transgenic mice following oral administration of ABC; this increase was associated with the severity of skin toxicity. In ABC-fed CD4+ T cell-depleted B*57 : 01-Tg/PD-1-/- mice, TARC was detected in the epidermal keratinocytes of the ear. Skin toxicity was characterized by the infiltration of CD8+ T cells partially expressing C-C chemokine receptor type 4, which is the primary receptor for TARC. In vivo TARC neutralization effectively alleviated the symptoms of ear skin redness and blood vessel dilatation. Moreover, TARC neutralization suppressed the infiltration of CD8+ T cells to the ear skin but did not affect the ABC-induced adaptive immune response. Therefore, TARC was involved in ABC-induced skin toxicity and contributed to the recruitment of CD8+ T cells to skin. This evidence suggests that serum TARC level may be a functional biomarker for AHS.

Skin disorder management in oral anticancer drugs by collaboration of hospital pharmacists and community pharmacists

BackgroundIn Japan, the multidisciplinary team approach in cancer chemotherapy has become quite widespread. However, patients treated with oral anticancer drugs in outpatient clinics usually receive short medical examinations from doctors without any intervention of pharmacists. To improve this medical circumstance, we made a skin disorder manual for community pharmacists and evaluated its feasibility.MethodsPatients who underwent oral skin toxic chemotherapy from May 1, 2017, to October 31, 2017, were enrolled. The severity of skin toxicities was evaluated based on NCI-CTCAE ver4.0. Skin care and skin disorders were assessed by community pharmacists based on the assessment document arranged by the investigator. Numbers of patients who replied to the assessment, numbers of replies, numbers of assessments and instructions for skin care, and numbers of prescription proposals were evaluated to assess the value of intervention of community pharmacists.ResultsSixty-two patients were enrolled in this study. Community pharmacy responded to 55 patients (88.7%), for a total of 335 replies. The data described in the replies were as follows: 317 assessments of skin disorders (94.6%), 307 assessments of skin care (91.6%), 248 instructions for skin care (74%), and 19 prescription proposals (5.7%).ConclusionsCommunity pharmacists have high motivation for prevention and early detection of skin disorders. Although the number of prescription proposals is small, some proposals have contributed to improving side effects. Collaboration of hospital pharmacists and community pharmacists is important for prevention, early detection, and treatment of skin disorders caused by oral anticancer drugs.

EGFRI-associated health-related quality of life by severity of skin toxicity in metastatic colorectal cancer patients receiving epidermal growth factor receptor inhibitor target therapy

The purposes of this study were to assess the levels of symptom distress, body image, and epidermal growth factor receptor inhibitors (EGFRI)-associated health-related quality of life (QoL); identify the factors related to EGFRI-associated health-related QoL; and examine the differences in EGFRI-associated health-related QoL by grade of skin toxicity in mCRC patients receiving target therapy. This cross-sectional study examined mCRC patients who received cetuximab-based target therapy from the oncology and CRC inpatient and outpatient departments of a medical center in northern Taiwan. Structured questionnaires were used to measure patients' symptom distress, body image, and EGFRI-associated health-related QoL. Of the 111 mCRC patients studied, 79.2% reported acneiform eruption and 52.2% reported paronychia. The most common symptoms were dry skin and itching. Poor EGFRI-associated health-related QoL was associated with more symptom distress, more negative body image, a higher cumulative dose of target therapy, and being married; these factors explained 66.6% of the variance in EGFRI-associated health-related QoL. Patient-specific skin care and emotional support are needed to relieve distressful dermatological symptoms and emotional distress during and post-treatment for mCRC.

Hand Foot Syndrome Has the Strongest Impact on QOL in Skin Toxicities of Chemotherapy.

Background: Chemotherapy often results in dermatologic toxicities, which decrease quality of life (QOL) of cancer patients. These adverse skin reactions sometimes happen simultaneously. Though previous reports have demonstrated that skin reactions influence QOL, those reports were focused on only one kind of skin toxicity or on the most serious skin toxicity. The aim of this study is to demonstrate the contribution of each skin toxicity to QOL.Methods: This is a cross-sectional study at Kinki Central Hospital. Patients were enrolled who underwent skin toxic chemotherapy from April 1 to June 30, 2017. DLQI and Skindex29 were used to grade the QOL of patients. Also, the severity of skin toxicities was evaluated based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE ver4.0). We investigated how QOL changed with patient demographic and clinical characteristics, the worst skin toxicity grade, and each skin toxicity using statistical analyses.Results: No significant differences were detected between QOL scores (total score of DLQI, emotions domain, symptoms domain, functioning domain and total score of Skindex29) and patient demographic and clinical characteristics (P values were 0.155, 0.086, 0.052, 0.312 and 0.114, respectively). There were statistically significant QOL differences among the grades of the worst skin toxicity (P values were <0.001). Xerosis, paronycia, pigmentation, and hand foot syndrome showed statistically significant associations with some QOL domains analyzed by multiple logistic regression analyses adjusted by demographic characteristics. When adjusted by both demographic characteristics and other skin toxicities, three of xerosis, paronycia, and pigmentation showed no statistically significant associations, but hand foot syndrome showed statistically significant associations in all subdomains and total score of Skindex29 (P values were <0.05).Conclusions: Hand foot syndrome was a stronger factor in decreasing QOL than xerosis, paronychia, pigmentation, or rash. Therefore, especially in hand foot syndrome, prevention, early detection, and daily medical care are necessary to maintain QOL.

Genome wide association study to identify predictors for severe skin toxicity in colorectal cancer patients treated with cetuximab.

EGFR-antibodies are associated with significant skin toxicity, including acneiform rash and folliculitis. It remains impossible to predict the occurrence of severe skin toxicity due to the lack of predictive markers. Here, we present the first genome-wide association study (GWAS) to find single nucleotide polymorphisms (SNPs) associated with EGFR inhibitor-induced skin toxicity using data of the multicentre randomized phase III CAIRO2 trial (clinicaltrials.gov NCT00208546). In this study, advanced or metastatic colorectal cancer patients were treated with capecitabine, oxaliplatin and bevacizumab with or without cetuximab. Germline DNA was available in 282 of the 368 patients in the cetuximab arm. Mild skin toxicity occurred in 195 patients (i.e. CTC grade 1 or 2, respectively 91 and 104 patients) and severe skin toxicity (i.e. grade 3) in 36 patients. Grade 4 skin toxicity did not occur. None of the SNPs reached the formal genome wide threshold for significance of 5x10-8, though SNPs of at least 8 loci did show moderate association (p-value between 5x10-7 and 5x10-5) with the occurrence of grade 3 (severe) skin toxicity. These SNPs did not overlap with SNPs associated with cetuximab efficacy as found in a previous GWAS in the same CAIRO2 cohort. If formally proven by replication, the SNPs associated with severe EGFR induced skin toxicity may be helpful to predict the occurrence and severity of skin toxicity in patients that will receive cetuximab and allow for adequate information on the risk of skin toxicity and prophylactic measurements.

Acute radiodermatitis in modern adjuvant 3D conformal radiotherapy for breast cancer - the impact of dose distribution and patient related factors

PurposeThis study was performed to evaluate skin toxicity during modern three-dimensional conformal radiotherapy (3D-CRT) and to evaluate the importance of dose distribution and patient related factors.Material and methodsThis study comprises 255 patients with breast cancer treated with tangential three-dimensional conformal radiotherapy (3D-CRT) after breast conserving surgery between 03/2012 and 05/2017. The median prescribed dose was 50.4 Gy (range 50–50.4) and 92.2% of the patients received a sequential boost of 10–16 Gy. Adverse skin toxicities (according to CTCAE v. 4.03 and the occurrence of moist desquamations) were assessed at the end of treatment. The dose distribution in the skin (5 mm strip from the patient outline) and in the CTV was evaluated and correlated to the CTCAE scores and the occurrence of moist desquamation.Results42.4% of the patients developed grade I, 55.7% grade II and 2% grade III skin toxicities. Moist desquamation was observed in 59 cases (23.1%). Dose distribution within the CTV and skin was homogenous with only small areas receiving 107% of the prescribed dose (median: 0.7 cm3) in the CTV and 105% (median 0.5 cm3) in the skin. On univariate analysis breast size as well as V107%(CTV), V105%(skin) and V80%(skin) correlated significantly (p < 0.05) with the incidence of skin toxicity. On multivariate analysis only V80%(skin) was confirmed as independent risk factor.ConclusionModern tangential multi-field 3D-CRT allows a homogeneous dose distribution with similar skin toxicity as compared to studies performing IMRT. Dose distribution within the skin (V80%) might have a relevant impact on the severity of skin toxicity and the occurrence of moist desquamation.

Compared with intensity-modulated radiotherapy, image-guided radiotherapy reduces severity of acute radiation-induced skin toxicity during radiotherapy in patients with breast cancer.

Radiotherapy (RT) is an effective treatment for breast cancer. The side effects of breast irradiation, including skin toxicity in the irradiation field, cause considerable discomfort. This study compared the severity of skin toxicity caused by image‐guided RT (IGRT) and intensity‐modulated RT (IMRT) combined with an electronic portal imaging device (EPID) in breast cancer. This study retrospectively analyzed 458 patients with breast cancer who had received RT. The patients were divided into two groups: 302 and 156 patients in the IMRT and IGRT groups. In the IGRT group, 8 and 148 patients had received helical tomotherapy irradiation and IMRT with cone‐beam computed tomography. Simple and multiple logistic regression analyses were used to estimate the relationship between RT technique and the severity of radiation skin toxicity. In our study, 284, 97, and 6 patients exhibited grades I, II, and III radiation dermatitis (RD). Moreover, 75 patients in the IMRT group (24.80%) and 22 patients in the IGRT group (14.10%) exhibited grade II RD. All patients with grade III RD were in the IMRT group (2.00%). No patient exhibited grade IV RD. The patients in the IGRT group exhibited less severity of RD than in the IMRT group. The severity of acute RD due to IGRT is significantly lower than that due to IMRT with EPID.

Impact of dermatologic adverse reactions on QOL in oncologic patients: results from a single-center prospective study.

Skin toxicity in patients receiving novel therapeutic cancer agents has become a very important marker in determining drug activity, but it can also severely impact their quality of life. About half of the patients receiving this type of oncologic treatment will develop cutaneous reactions, that is why adequate understanding and management of these side effects is very important for drug adherence and patients' quality of life. We conducted a prospective study of consecutive patients who received oncologic treatment in our institution and presented with dermatologic side effects. The severity of skin toxicity was assessed using the DLQI score and patients were prospectively followed to evaluate response to therapy. Univariate analysis of factors influencing the impact of skin toxicity on patient QOL was conducted. 52 patients were enrolled in the study. Patients who developed grade 3 and 4 skin toxicity had a higher DLQI score, with a greater impact on quality of life, but with better clinical outcome at 3 months follow-up, based on RECIST. Patients with moderate or severe cutaneous AE were more likely to achieve complete or partial response to therapy than those with mild AE (16/33 vs. 3/19, p = 0.035). Interestingly, female patients had a significantly poorer quality of life than male patients as assessed by the DLQI score (7.28 ± 7 vs. 3.7 ± 3.6, p = 0.038). Cutaneous side effects are often encountered in cancer patients and their severity can be a surrogate marker for a positive clinical tumor response to therapy.

Adverse Reactions to Biologics: Melanoma (Ipilimumab, Nivolumab, Pembrolizumab).

With increasing use of immunotherapies such as anti-cytotoxic T cell lymphocyte antigen-4 and anti-programmed cell death 1 antibodies, various skin toxicities have emerged. Severity of skin toxicities varies from mild lichenoid reaction to severe toxic epidermal necrolysis. Appropriate diagnosis and management of these skin toxicities are essential for optimal patient care and to avoid unnecessary cessation of anti-cancer therapies. This review summarises a wide range of cutaneous manifestations associated with immunotherapy usage in patients with metastatic melanoma.

Skin toxicity evaluation in patients treated with cetuximab for metastatic colorectal cancer: a new tool for more accurate comprehension of quality of life impacts

ObjectivesThe effectiveness of evaluation of the severity of epidermal growth-factor receptor inhibitor (EGFRI)-associated dermatological toxicities remains a topic of debate. This study was designed to assess the correlation between quality of life (QoL) and severity of dermatological toxicity, evaluated using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE) and our novel scale, the Eruption Scoring System (ESS), in metastatic colorectal cancer (CRC) patients treated with first-line chemotherapy combined with cetuximab.MethodsCutaneous toxicity was evaluated, by oncologists and dermatologists, in patients (n=30) with histologically confirmed metastatic CRC who were scheduled to begin first-line chemotherapy combined with the EGFRI, cetuximab, using the NCI-CTCAE and ESS tools. Health-related QoL (HRQoL) was evaluated using the Skindex-29 and Skindex-17 dermatology-specific instruments. Correlations between QoL and skin toxicity severity were assessed using Spearman’s rank tests. Interclass correlation coefficients were used to assess interoperator agreement for ESS and NCI-CTCAE v4.0 scoring.ResultsA positive correlation was identified between dermatology HRQoL and the severity of dermatological toxicities assessed using the NCI-CTCAE v4.0 scale for cutaneous papulopustular acneiform rash; however, a stronger correlation was observed between HRQoL and toxicities evaluated using the ESS tool. Both NCI-CTCAE v4.0 and ESS tools demonstrated good interobserver agreement for grading of skin toxicity.ConclusionThere is a strong correlation between the scores generated by the ESS and NCI-CTCAE tools to grade cutaneous toxicity related to treatment with the anti-EGFR monoclonal antibody, cetuximab. ESS can be considered a valid instrument for identification and grading of the severity of skin toxicity induced by cetuximab, with some advantages over the standard NCI-CTCAE scoring system.

2110 Efficacy outcomes by severity of skin toxicity from ASPECCT: Randomized phase 3 study of panitumumab (pmab) versus cetuximab (cmab) in chemorefractory wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC)

2110 Efficacy outcomes by severity of skin toxicity from ASPECCT: Randomized phase 3 study of panitumumab (pmab) versus cetuximab (cmab) in chemorefractory wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC)

Predictability of antitumor efficacy of cetuximab plus irinotecan based on skin rash severity according to observation period in patients with metastatic colorectal cancer following failure of fluorouracil, irinotecan and oxaliplatin

The efficacy of cetuximab correlates with the severity of skin toxicity, although its onset may vary. The AIM of this retrospective study was to investigate the optimal observation period for skin rash as a predictor of the efficacy of cetuximab plus irinotecan. The subjects comprised 33 patients with KRAS wild-type metastatic colorectal cancer (mCRC) who had received prior chemotherapy with fluorouracil, irinotecan and oxaliplatin. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were compared according to the presence or absence of ≥grade 2 skin rash within 2, 4, 6, or 8 weeks following cetuximab initiation. The overall RR was 45% (15/33) and the median PFS and OS were 188 and 383 days, respectively. A total of 26 patients experienced ≥grade 2 skin rash within 8 weeks. The proportion of responders among patients who developed ≥grade 2 skin rash (severe group) decreased depending on the duration of the observation period (50% within 8 weeks), whereas the proportion of non-responders among patients with <grade 2 skin rash (mild group) increased (71% within 8 weeks). Similarly, the proportion of patients with an unfavorable prognosis (PFS <6 months, OS <1 year) in the mild group increased (86% for PFS and 71% for OS within 8 weeks), whereas the proportion of those with a favorable prognosis in the severe group remained stable (73% for PFS and 62% for OS within 8 weeks). Therefore, the absence of ≥grade 2 skin rash within 8 weeks may be predictive of unfavorable efficacy of cetuximab plus irinotecan in mCRC patients.

Quality of life (QoL) during first-line treatment with FOLFOX4 with or without panitumumab (pmab) in RAS wild-type (WT) metastatic colorectal carcinoma (mCRC).

693 Background: The benefits of anti-cancer treatment must be balanced with the impact of adverse events on QoL. In the PRIME study, first-line pmab + FOLFOX4 significantly improved overall survival vs. FOLFOX4 in patients (pts) with RAS WT (KRAS/NRAS WT exons 2, 3 and 4) mCRC, but was associated with typical EGFR inhibitor adverse events. Here we report pre-specified tertiary QoL endpoints for pts with RAS WT mCRC. Methods: PRIME was a randomised open-label phase III study of first-line pmab 6.0 mg/kg Q2W + FOLFOX4 vs. FOLFOX4 in mCRC pts. QoL was assessed every 4 weeks until disease progression, and once at safety follow-up, using the EuroQoL 5-domain (EQ-5D) health state index (HSI) and overall health rating (OHR; 0–100 visual analogue scale). Differences were assessed from baseline to disease progression, and to discontinuation of first-line treatment, using analysis of covariance (ANCOVA) and a mixed-effect piecewise linear model. Analysis of QoL by skin toxicity severity is also planned. Results: 505 pts had RAS WT mCRC; overall compliance rates (evaluable vs. expected assessments) were 57% for both HSI and OHR. When analysed by ANCOVA there were no significant differences between the pmab + FOLFOX4 and FOLFOX4 arms from baseline to progression (Table) or to discontinuation. In the mixed-effect model, there were no significant differences between pmab + FOLFOX4 and FOLFOX4 in terms of HSI (overall test of difference between arms from baseline to discontinuation, p=0.2433; baseline to progression, p=0.5364) or OHR (p=0.1312 and 0.1290, respectively). Significant differences in favour of pmab + FOLFOX4 were reported in the baseline to discontinuation analysis at week 8 for HIS (p=0.0267) and OHR (0.0137) and week 12 for OHR (p=0.0187), and in the baseline to disease progression analysis at week 16 for OHR (p=0.0163) (Table). Conclusions: Addition of pmab to FOLFOX4 in first-line mCRC improves OS with no negative effect on overall QoL. Clinical trial information: NCT00364013. [Table: see text]

Racial Variations in Radiation-Induced Skin Toxicity Severity: Data From a Prospective Cohort Receiving Postmastectomy Radiation

Radiation-induced skin toxicity is one of the most symptomatic side effects of postmastectomy radiation therapy (PMRT). We sought to determine whether the severity of acute skin toxicity was greater in black patients in a prospective cohort receiving PMRT and to identify other predictors of more severe skin toxicity. We evaluated the first 110 patients in an ongoing prospective study assessing radiation-induced skin toxicity in patients receiving PMRT. We recorded patient demographics, body mass index (BMI), and disease and treatment characteristics. Logistic regression analyses were conducted to evaluate the effect of potential predictors on the risk of skin toxicity. A total of 23.6% respondents self-identified as black, 5.5% as non-Hispanic white, 69.1% as Hispanic white, and 1.8% as other; 57% were postmenopausal, and 70.9% had BMI of >25. Median chest wall dose was 50 Gy, and mastectomy scar dose was 60 Gy. Most patients, 95.5%, were treated with a 0.5-cm bolus throughout treatment. There were no significant differences in patient characteristics in black versus non-black patients. At RT completion, moist desquamation was more common in black patients (73.1% vs 47.6%, respectively, P=.023), in postmenopausal patients (63.5% vs 40.4%, respectively, P=.016), and in those with BMI of ≥25 (60.3% vs 37.5%, respectively, P=.030). On multivariate analysis, the effects of black race (odds ratio [OR] = 7.46, P=.031), BMI ≥25 (OR = 2.95, P=.043) and postmenopausal status (OR = 8.26, P=.004) remained significant risk factors for moist desquamation. In this prospectively followed, racially diverse cohort of breast cancer patients receiving PMRT delivered in a uniform fashion, including the routine use of chest wall boost and bolus, black race, higher BMI, and postmenopausal status emerged as significant predictors of moist desquamation. There was a high frequency of moist desquamation, particularly in those patients with elevated risk. Continued study of patient selection for chest wall boost and bolus as well improved skin toxicity management strategies are needed.

552P - Randomized Controlled Trial on the Skin Toxicity of Panitumumab in Third Line Treatment of Kras Wild-Type Metastatic Colorectal Cancer: Hgcsg1001 (Japanese Skin Toxicity Evaluation Protocol with Panitumumab: J-Stepp): Additional Analysis of Qol and Skin Toxicity

ABSTRACT Aim: Panitumumab (Pmab) has demonstrated efficacy in patients with KRAS wild-type metastatic colorectal cancer (mCRC). Although the STEPP study (Lacouture M. E. et al. J Clin Oncol. 2010; 28: 1351-7.) showed that pre-emptive skin treatment reduced skin toxicities compared with reactive treatment among patients receiving Pmab, data for Asians has not been reported. We planned a randomized, open-label trial to verify the differences between pre-emptive and reactive treatment for skin toxicities in Japanese patients. Methods: Patients receiving third-line Pmab-containing regimens for mCRC were randomly assigned 1:1 to pre-emptive (skin moisturizers, sunscreen, topical steroid, and minocycline) or reactive (only skin moisturizers) skin treatment. The primary endpoint was the cumulative incidence of ≥grade 2 skin toxicities during the 6-week treatment period. Retrospectively, a dermatologist reviewed skin toxicities, in a blinded manner, using photographs. Results: Of 95 enrolled patients, 47 were assigned to pre-emptive, and 48 to reactive treatment. The incidence of ≥grade 2 skin toxicities during the 6-week treatment period (investigators’ assessment) was 21.3% and 62.5% (risk ratio [RR], 0.34; 95% CI, 0.19 to 0.62; P Conclusions: Although pre-emptive skin treatment could not be affected with QOL, it could reduce the severity of skin toxicities during Pmab treatment. Our data clearly validate that pre-emptive treatment can also be recommended in Japanese patients. Disclosure: M. Nakamura: Takeda Pharmaceutical, Chugai Pharmaceutical, Bayer Yakuhin; S. Yuki: Taiho Pharmaceutical, Chugai Pharmaceutical, Bristol-Myers Squibb, Merck Serono, Takeda Pharmaceutical, Yakult Honsha; Y. Sakata: Taiho Pharmaceutical, Daiichi Sankyo, Yakult Honsha, Otsuka Pharmaceutical, Merck Serono, Bristol-Myers Squibb, Synergy International; Y. Komatsu: Yakult Honsha, Taiho Pharmaceutical, Chugai Pharmaceutical, Merck Serono, Pfizer Japan, Novartis Pharma, Sawai Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Eli Lilly Japan, Kureha Corporation. All other authors have declared no conflicts of interest.

Timing and severity of skin-related adverse events in a phase II trial of sorafenib (BAY43-9006) in patients with advanced thyroid cancer.

e17009 Background: We previously conducted a phase II study of sorafenib (BAY43-9006) in advanced thyroid cancer. Rash and Hand-Foot Skin Reaction (HFSR) were two of the most common adverse events (AEs). Because these skin-related AEs affect quality of life, we further explored their time course and management. Methods: Fifty-five patients were treated on UPCC 03305, a phase II study of sorafenib in patients with advanced thyroid cancer from 2006 to 2011. AEs were recorded using CTCAE v.3.0 and reported here if relation to the drug was deemed “possibly-related” or greater. Cycle length was four weeks. Results: No grade 4 or 5 skin toxicity was observed. Forty-nine patients (89%) experienced rash. Thirty-one patients had a maximum severity of grade 1 (56%), eight had grade 2 (15%), and nine had grade 3 (18%). Fifty patients (91%) had HFSR. Thirteen patients had a maximum severity of grade 1 (24%), 33 had grade 2 (60%), and four had grade 3 (7%). The severity of rash peaked at cycle 1 (19% grade 2,3) and declined by cycle 3 (4% grade 2,3). The severity of HFSR peaked at cycle 2 (39%, grade 2,3) and declined by cycle 6 (10% grade 2,3). The timing and severity of rash and HFSR by cycle are reported in the Table. Following cycle 12 the severity and prevalence of skin AEs reached a steady state. Of the 55 patients, 30 patients (55%) required dose-reduction, and nine of those patients (31%) resumed full dose by the end of study date. Nine patients (16%) were dose-reduced for rash, 17 patients (31%) were dose-reduced for HFSR, and three patients (5%) were dose-reduced for both rash and HFSR. Conclusions: The severity of skin toxicity peaked by cycle 1 for rash and cycle 2 for HFSR. The severity improved dramatically for rash by cycle 3 and for HFSR by cycle 6. Our data support the close supervision of skin-related AEs in the first six cycles of treatment with sorafenib. However, the sustained high prevalence of rash and HFSR requires all patients receive ongoing skin care for the duration of therapy. Clinical trial information: NCT00095693. [Table: see text]

Skin toxicity and quality of life in patients with metastatic colorectal cancer during first-line panitumumab plus FOLFIRI treatment in a single-arm phase II study

BackgroundIntegument-related toxicities are common during epidermal growth factor receptor (EGFR)-targeted therapy. Panitumumab is a fully human monoclonal antibody targeting the EGFR that significantly improves progression-free survival when added to chemotherapy in patients with metastatic colorectal cancer who have wild-type (WT) KRAS tumours. Primary efficacy and tolerability results from a phase II single-arm study of first-line panitumumab plus FOLFIRI in patients with metastatic colorectal cancer have been reported. Here we report additional descriptive tolerability and quality of life data from this trial.MethodsIntegument-related toxicities and quality of life were analysed; toxicities were graded using modified National Cancer Institute Common Toxicity Criteria. Kaplan-Meier estimates of time to and duration of first integument-related toxicity were prepared. Quality of life was measured using EuroQoL EQ-5D and EORTC QLQ-C30. Best overall response was analysed by skin toxicity grade and baseline quality of life. Change in quality of life was analysed by skin toxicity severity.Results154 patients were enrolled (WT KRAS n = 86; mutant KRAS n = 59); most (98%) experienced integument-related toxicities (most commonly rash [42%], dry skin [40%] and acne [36%]). Median time to first integument-related toxicity was 8 days; median duration was 334 days. Overall, proportionally more patients with grade 2+ skin toxicity responded (56%) compared with those with grade 0/1 (29%). Mean overall EQ-5D health state index scores (0.81 vs. 0.78), health rating scores (72.5 vs. 71.0) and QLQ-C30 global health status scores (65.8 vs. 66.7) were comparable at baseline vs. safety follow-up (8 weeks after completion), respectively and appeared unaffected by skin toxicity severity.ConclusionsFirst-line panitumumab plus FOLFIRI has acceptable tolerability and appears to have little impact on quality of life, despite the high incidence of integument-related toxicity.Trial registrationClinicalTrials.gov NCT00508404