Hand-foot skin reaction

Sorafenib is a multikinase inhibitor that inhibits both intracellular and extracellular kinases to decrease renal cell cancer proliferation. The half-life of sorafenib is 25 to 48 hours, with a bioavailability of 38% to 49% and a time to peak concentration of 3 hours. Sorafenib is metabolized primarily by the liver by CYP450 3A4. Sorafenib is used for the treatment of renal cell cancer. The primary side effects of sorafenib include rash, hand-foot skin reaction, diarrhea, pruritus, and elevations in serum lipase. 

A recent multi-institution survey in Japan drew attention to an important effect of histamine H2 antagonists on docetaxel-induced skin toxicity. Analyses revealed that administration of H2 blockers was associated with a significantly higher incidence of acral erythema (hand-foot syndrome palmar-plantar erythrodysesthesia compare with hand-foot skin reaction. Sects. 13.3.2 and 13.3.3 and see Fig. 13.1) and facial erythema. Steroids and H2 blockers affect the metabolism of docetaxel by cytochrome P45o3A4 (CYP3A4), but dexamethasone dosage did not change the incidence of hand-foot syndrome or facial edema. 

A phase I study of Xeloda in combination with XRT in rectal cancer is in the adjuvant, neoadjuvant, and palliative settings (71-73). The DLT of the combination is hand-foot syndrome and mild to moderate leukopenia, diarrhea, and local skin reaction (71-73). The recommended dose for phase 2 studies is Xeloda 825 mg/m2 twice daily without interruption in combination with standard dose of radiation. Promising activity has been demonstrated in neoadjuvant therapy with six objective responses in seven evaluable patients including one pathological confirmed CR. 

Skin Cutaneous reactions to fluorouracil include photosensitivity, erythema, maculo-pamlar rashes, and hyperpigmentation [8 ]. Alopecia is uncommon. Hand-foot syndrome affects about 50% of patients but it is usually mild. It occurs after a median of nine cycles of treatment and necessitates dosage reduction or delay in 15% of patients [90 ]. It is less frequent with bolus doses than infusions [83 ]. 

Skin and subcutaneous tissue disorders Reversible cutaneous reactions have been observed and are generally mild to moderate. Reactions are characterised by a rash including localised eruptions mainly on the feet and hands (including severe hand and foot syndrome), but also on the arms, face or thorax, and frequently associated with pruritus. Eruptions generally occur within one week after the docetaxel infusion. Severe nail disorders are characterised by hypo- or hyperpigmentation and sometimes pain and onycholysis. 

HT is relatively more potent than histamine in increasing vascular permeability in the rat [61, 137, 414, 485, 487, 534, 578, 581]. Parratt and West [482-490] extensively studied the significance of the presence of the substantial amounts of both 5-HT and histamine in the skin and subcutaneous tissues of the rat, and the importance of their release from these sites during the anaphylactoid reaction. Polymyxin B sulphate released more than 90% of the histamine in the rat skin but less than 20% of its 5-HT on the other hand, reserpine released more than 90% of the 5-HT but only small amounts of the histamine. Pretreatment with reserpine, but not with polymyxin B sulphate, effectively inhibited both the egg-white and dextran anaphylactoid reaction. Further evidence for an important role of 5-HT in the anaphylactoid reaction was obtained when it was found that after an intraperitoneal injection of egg-white or dextran 5-HT, but not histamine, was present in the oedema fluid associated with the subcutaneous tissues on the dorsal side of the foot. 

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