**4. Other targets**

over 50% reduction in grade ≥ 2 skin toxicities and less QoL impairment with the pre-emptive compared with reactive treatment [103]. In cases of grade 3 rash, treatment should be delayed until toxicity has resolved to grade 2 or less and dose should be reduced in a second occurrence. In grade 1 or 2 rash, dose reduction is not indicated. Other dermatological symptoms, including hair growth, periungual and nail plate abnormalities, xerosis, telangiectasias, and pruritus can occur at lower

Infusion reactions commonly occur with cetuximab and should be prevented with premedication, antihistamines, and corticosteroids. Other adverse effects, like hypomagnesemia, ocular toxicities as conjunctivitis and blepharitis, and less commonly diarrhea, can also occur [104]. Toxicity management is grade-depend and, in

The main anti-VEGF side effects are cardiovascular and kidney problems (**Table 3**). Hypertension has been observed at high rates in all phase III studies of anti-VEGF drugs and is normally manageable with standard antihypertensive medications, but this treatment should not be initiated in patients with uncontrolled hypertension. Proteinuria is another side effect, defined as protein content in the urine >300 mg/dL. No standard treatment is established, but anti-angiogenic drugs should be disused if protein content in the urine is >2 g/24 h, and evaluation by a nephrologist should be considered. Hand-foot syndrome is also common with this

Bevacizumab has also been associated with other side effects, like thromboembolic events (8%), delayed wound healing, bleeding, fistulae, and gastrointestinal

> Skin moisturizer, sunscreen, hydrocortisone cream, and oral tetracycline

Antihistamines and corticosteroids Low rate, gradual titration

electrolyte replacement, hospitalization

Blood pressure monitoring, antihypertensive drugs

angiotensin receptor blockers

*A, aflibercept; B bevacizumab; C cetuximab; EGFR, epidermal growth factor receptor; G grade; P, panitumumab;*

B 8% Anticoagulation therapy Cease bevacizumab

**Prevention/treatment Dose reduction/delay**

Magnesium replacement Some G3/4 toxicity delay

Emollient, analgesia Reduction in 1st G3 or 2nd

**treatment**

Reduction in 2nd G3 occurrence, delay until ≤ G2

Grade dependent

until recovery

Reduction in 1st G3 or 2nd G2 occurrence

Cease if G4 or persisting G3 toxicity

Discontinue if nephrotic syndrome

G2 occurrence, delay until ≤ G1

some cases, should be addressed by a multidisciplinary team.

**incidence**

P 20–50%

P-3%

P 27%

A 42.4% Reg 15% Ram 11%

B 16% Reg 14%

*Ram, ramucirumab; Reg, regorafenib, VEGF, vascular endothelial growth factor.*

*Adverse effects of any severity with anti-EGFR and -VEGF therapies.*

Diarrhea 2% G3/4 Loperamide, hydration,

Proteinuria 18.7% Screening for proteinuria

rates [102].

*Colorectal Cancer*

class of drugs [105].

**Target Effect Drug-**

EGFR Rash C 52–89%

Infusion reactions C 14–21%

Hypomagnesemia C 4–38%

VEGF Hypertension B 25%

Hand-foot syndrome

Thromboembolic events

**Table 3.**

**142**
