-Characteristics of the study population
A total of 131 patients were eligible for the study, and 17 declined to participate. Thus, 114 patients were included in the study. Demographic and clinical characteristics of study population are summarized in Table 1.
Table 1
Demographic and clinical characteristics
Variable | Total (n = 114) |
Gender, n (%) - Male - Female | 49 (43.0) 65 (57.0) |
Age at diagnosis, years - Mean (SD) - Median (IQR) | 59.9 (11.7) 62.5 (50.3–68.5) |
Tumor type, n (%) - Gastrointestinal - Breast - Lung - Urological/renal - Gynecologic - Other | 42 (36.8) 33 (28.9) 19 (16.7) 11 (9.6) 4 (3.5) 5 (4.4) |
Tumor stage, n (%) - Stage 2 - Stage 3 - Stage 4 | 11 (9.6) 16 (14.0) 87 (76.3) |
Treatment type, n (%) - Conventional chemotherapy - Targeted therapy - Combined therapy (targeted + chemotherapy) | 46 (40.3) 44 (38.6) 24 (21.0) |
Type of dichotomous treatment, n (%) - Conventional chemotherapy - Targeted therapy + Combined therapy (targeted + chemotherapy) | 46 (40.3) 68 (59.6) |
Previous lines of treatment, n - Mean (SD) - Median (IQR) | 1.46 (0.96) 1 (1–2) |
Treatment duration, months - Mean (SD) - Median (IQR) | 6.7 (6.5) 4 (2–9) |
Previous dermatological disease * - No - Yes | 110 (96.5) 4 (3.5)* |
ECOG Performance Status - 0 (Asymptomatic) - 1 (Symptomatic, but completely ambulatory) - 2 (Symptomatic, < 50% of time in bed) - 3 (Symptomatic, > 50% of time in bed) | 2 (1.7) 89 (78.1) 21 (18.4) 2 (1.7) |
* Four patients presented previous dermatological disease including psoriasis (2 patients), paraneoplastic dermatomyositis and simple chronic lichen (1 patient each) |
-Type of treatment
Regarding classic chemotherapy medicines, the most frequently drugs were part of schemes that included 5-FU or derivatives in combination with oxaliplatin or irinotecan (41.9%), followed by taxanes in monotherapy (20.9%), regimes with anthracyclines and alkylating agents (14.8% ), schemes with platinum salts and taxanes, vinca alkaloids or others (12.3%), and others (9.8%).
Of targeted therapies, immunotherapy (27%) was the most frequently used, followed by EGFR inhibitors (21%), VEGF inhibitors (17%), multi-kinase inhibitors (14%), HER2 inhibitors (13%), and others (8%).
-Identified Cutaneous Adverse Events
Among the 114 patients included, the total number of CAEs was 177. The most frequent CAEs were pruritus, xerosis, palmar-plantar erythrodysesthesia (PPE), alopecia and papulopustular eruption (Table 2). Regarding the number of CAEs, a majority of patients reported one CAE (56.1%), while 37 (32.5%) and 13 (11.4%) subjects had two or three CAEs, respectively.
Table 2
Cutaneous Adverse Events (CAEs)
Variable | Total (177 CAEs) |
Type of CAE, n (%) - Pruritus - Xerosis - Palmar-plantar erythrodysesthesia (PPE) - Alopecia - Papulopustular eruption - Ungual apparatus lesions - Pigmentary changes - Rash - Hand foot skin reaction (HFSR) - Photosensitivity - Other* | 29 (16.3) 24 (13.5) 24 (13.5) 21 (11.8) 17 (9.6) 13 (7.3) 13 (7.3) 9 (5.0) 6 (3.3) 6 (3.3) 15 (8.4) |
Number of CAE, n (%) - Patients with only one CAE - Patients with two CAEs - Patients with three CAEs | 64 (56.1) 37 (32.5) 13 (11.4) |
Severity of CAE, n (%) - Grade 1 - Grade 2 - Grade 3 - Grade 4 | 112 (63.2) 53 (29.9) 12 (6.7) - |
*Other: bullous pemphigoid, eyelid edema, telangiectasis, purpura, hypertrichosis, trichomegaly, folliculitis, balanitis |
According to severity of CAEs, most patients experienced CAEs grade 1 (54.3%), while 35.1% and 10.5% experienced CAEs grade 2 and 3, respectively. No grade 4 CAE were observed.
-Quality of life indices
Mean (SD) score of total study population in FACT-G was 65.3 (13.4). We did additional sub-analysis according to the specific domains of FACT-G. Scores according to Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB) domains are presented in Table 3.
Table 3
Indices | Total (114) |
FACT-G - Mean (SD) - Median (IQR) | 65.3 (13.4) 66 (57–74) |
Subscale Physical Well-Being (PWB) - Mean (SD) - Median (IQR) | 17.2 (5.0) 17 (14–21) |
Subscale Social/Family Well-Being (SWB) - Mean (SD) - Median (IQR) | 19.3 (4.3) 20 (17–21) |
Subscale Emotional Well-Being (EWB) - Mean (SD) - Median (IQR) | 14.3 (4.0) 14 (11–18) |
Subscale Functional Well-Being (FWB) - Mean (SD) - Median (IQR) | 14.5 (4.8) 14.5 (11–18) |
DLQI - Mean (SD) - Median (IQR) | 8.4 (5) 8 (5–12) |
SKINDEX-16 - Mean (SD) - Median (IQR) | 30.8 (16.9) 29 (19–44) |
Symptoms domain - Mean (SD) - Median (IQR) | 10.6 (6.1) 11 (6–15) |
Emotions domain - Mean (SD) - Median (IQR) | 15.0 (8.8) 13 (9–21) |
Functioning domain - Mean (SD) - Median (IQR) | 5.2 (5.7) 3 (0–8) |
Mean (SD) score of total study population in DLQI was 8.4 (5) while mean (SD) score of SKINDEX-16 was 30.8 (16.9). Additional sub-analyses were carried out according to the specific domains of SKINDEX-16. Scores of Symptoms, Emotions and Functioning domains can be seen in Table 3.
A total of 17 patients with anti-EGFR toxicities completed the FACT-EGFRI-18 questionnaire. The mean (SD) score of this subgroup was 47,2 (SD 13,2). In this group, mean (SD) values of FACT-G, DLQI and SKINDEX-16 were 64.1 (18.7), 8.4 (4.5) and 33.5 (19.7), respectively.
Quality of life (QoL) indices and differences between conventional chemotherapy vs. targeted therapy.
In our study, no significant differences in QoL indices (FACT-G, DLQI, SKINDEX-16) were observed according to the type of treatment (conventional chemotherapy vs Targeted therapy plus combined therapy). Mean (SD) and median (IQR) scores for Skindex-16 Symptoms, Emotions and Functioning domains are presented in Table 4.
Table 4
Quality of life (QoL) indices and differences between conventional chemotherapy vs targeted therapy.
| Total (n = 114) | Conventional chemotherapy (n = 46) | Targeted therapy + Combined therapy (n = 68) | p |
FACT-G - Mean (SD) - Median (IQR) | 65.3 (13.4) 66 (57–74) | 66.5 (13.2) 69 (58–73) | 64.1 (13.4) 61 (54–75) | 0.573 |
DLQI - Mean (SD) - Median (IQR) | 8.4 (5.0) 8 (5–12) | 7.7 (5.3) 7 (4–11) | 8.9 (4.8) 8 (5–12) | 0.160 |
SKINDEX-16 - Mean (SD) - Median (IQR) | 30.8 (16.9) 29 (19–44) | 29.2 (17.1) 28.5 (18–42) | 31.9 (16.8) 29.5 (19–44) | 0.477 |
Skindex symptoms - Mean (SD) - Median (IQR) | 10.6 (6.1) 11 (6–15) | 10.6 (6.8) 11 (5–16) | 10.5 (5.6) 11 (6–14) | 0.864 |
Skindex emotions - Mean (SD) - Median (IQR) | 15.0 (8.8) 13 (9–21) | 13.7 (8.8) 11 (8–18) | 15.9 (8.7) 15 (9–21) | 0.148 |
Skindex functioning - Mean (SD) - Median (IQR) | 5.2 (5.7) 3 (0–8) | 4.9 (5.4) 3 (0–8) | 5.5 (6.0) 3 (0–8) | 0.799 |
-Cutaneous toxicities and quality of life
Cutaneous toxicities related to QoL indices (FACT-G, DLQI and Skindex-16) are presented in Table 5.
Table 5
Cutaneous toxicities and quality of life
CAE | FACT-G Mean (SD) | DLQI Mean (SD) | SKINDEX 16 Mean (SD) |
- PPE | 61.0 (12.6) | 8.9 (3.6) | 31.1 (13.9) |
- Pruritus | 61.4 (14.1) | 7.5 (3.9) | 23.9 (14.8) |
- Papulopustular rash | 64.1 (18.7) | 8.4 (4.5) | 33.5 (19.7) |
- Alopecia | 62.6 (10.4) | 5.8 (4.4) | 24.6 (13.9) |
- Xerosis | 68.0 (7.9) | 5.3 (3.6) | 24.3 (23.7) |
- Ungual apparatus | 62.2 (14.9) | 6.2 (5.5) | 23.4 (15.1) |
- Rash | 63.1 (15.4) | 10.1 (7.4) | 40.3 (16.4) |
- HFSR | 60.7 (3.4) | 14.5 (4.4) | 45.6 (7.3) |
- Pigmentary changes | 73.1 (18.8) | 3.1 (6.0) | 10.0 (18.1) |
The CAEs that had the greatest impact on quality of life were HFSR, rash and PPE. Mean (SD) for HFSR was 14.5 (4.4) in DLQI and 45.6 (7.3) in Skindex-16, while mean (SD) for rash was 10.1 (7.4) in DLQI and 40.3 (16.4) in Skindex-16. Mean (SD) values for PPE were 8.9 (3.6) and 31.1 (13.9) in in DLQI and Skindex-16, respectively.
The CAEs that had the least impact were pigmentary changes, alopecia and xerosis. Pigmentary changes had mean (SD) scores of 3.1 (6.0) in DLQI and 10.0 (18.1) in Skindex-16, while alopecia had mean (SD) scores of 5.8 (4.4) in DLQI and 24.6 (13.9) in Skindex-16. Mean (SD) values for xerosis were 5.3 (3.6) and 24.3 (23.7) in in DLQI and Skindex-16, respectively.
-Other results
-Treatment interruption CAE related
Treatment interruption due to CAE was observed in 17/114 (14.91%) patients. Of those, 13/17 (76.47%) had DLQI ≥ 10 and 10/17 (58.82%) had 2 or more CAE.
Of those 17 treatment interruptions, 7 were associated to PPE and 4 to papulopustular lesions, while 2 interruptions were observed in patients with HFSR, 2 with rash, and 2 in subjects with ungual apparatus lesions. Regarding severity of CAE related to treatment interruption, 3/17 patients had a CAE grade 1, 9/17, and 5/17 had a CAE grade 2 and grade 3, respectively.
-Total number of CAEs per patient between treatment groups
No differences were found regarding the total number of CAE per patient between conventional chemotherapy vs targeted therapy (number of patients with 1 CAE: targeted therapy + combined therapya 38 vs conventional chemotherapy 26; number of patients with 2 or more CAEs: targeted therapy + combined therapy 30 vs conventional chemotherapy 20; p = 0.94).
-Patients with DLQI ≥ 10 and number of CAEs
Patients with 2 or more CAEs and patients with moderate to severe CAEs had significantly more impact on QoL as measured by DLQI vs patients with one or mild CAEs (Table 6).
Table 6
Patients with DLQI ≥ 10 and number of CAEs
Number of CAEs | Total (n = 114) | DLQI ≥ 10 (n = 43) | DLQI < 10 (n = 71) | P value |
- 1 CAE - 2 or more CAE | 64 50 | 16 27 | 48 23 | 0.002 |
- Mild (grade 1) - Moderate-severe (grade 2–3) | 62 52 | 15 28 | 47 24 | 0.002 |