Hand-foot syndrome

Capecitabine is used for the treatment of colorectal and breast cancers. It is contraindicated in patients with known hypersensitivity to capecitabine or any of its components or to 5-fluorouracil and in patients with known dihydropyrimidine dehydrogenase (DPD) deficiency. The use of capecitabine is restricted in patients with severe renal impairment. The drag can induce diarrhea, sometimes severe. Other side effects include anemia, hand-foot syndrome, hyperbilirubinemia, nausea, stomatitis, pyrexia, edema, constipation, dyspnea, neutropenia, back pain, and headache. Cardiotoxicity has been observed with capecitabine. A clinically important drag interaction between capecitabine and warfarin has been demonstrated. Care should be exercised when the drag is co-administered with CYP2X9 substrates. 

Children younger than 3 years of age can present with dactylitis (hand-foot syndrome), which is painful swelling of the hands and feet. 

Liposomal doxorubicin Myelosuppression, palmar-plantar erythrodysesthesia (hand-foot syndrome) Alopecia, infusion reactions, stomatitis, fatigue, nausea, vomiting... 

Fluorouracil Inhibition of the enzyme thymidylate synthase, the rate-limiting step in thymidine formation. Dose-limiting Myelosuppression and mucositis with bolus administration Diarrhea and hand-foot syndrome with continuous infusion Additional toxicities Skin discoloration, nail changes, photosensitivity, and neurologic toxicity... 

Warning signs to report to the physician (depends on regimen used) include fever, diarrhea, mucositis, and hand-foot syndrome. 

Doxorubicin 3 hours cycles 1 2 and then infused over 1 hour thereafter repeat every 28 days mucositis, alopecia, flushing, shortness of breath, hypotension, headaches, cardiotoxicity, hand-foot syndrome dysfunction. 2. Do not give if total bilirubin is greater than 5 mg/dL. 

Capecitabine 1 800-2500 mg/m2 PO as divided dose twice for 14 consecutive days, followed by 1 week of rest 29% Myelosuppression, hand-foot syndrome, nausea/vomiting, edema, stomatitis, diarrhea, cardiotoxicity, rash 1. Monitor for PPE and recommend regular use of lotions on hands and feet. 

Capecitabine -converted to 5-FU preferentially by tumor cells pyrimidine analogue antimetabolite inhibits thymidylate synthase -mucocutaneous effects (stomatitis, mucositis) -diarrhea -bone marrow suppression -nausea and vomiting -palmar-plantar erythrodysethesias (hand-foot syndrome) -fatigue... 

Continuous IV infusion of 5-FU is generally well tolerated but is associated with palmar-plantar erythrodysesthesia or hand-foot syndrome. This distinct skin toxicity can be acutely disabling, but it is reversible and not life threatening. IV bolus administration is associated with leukopenia, which is dose limiting and can be life threatening. Both methods are associated with a similar incidence of mucositis, diarrhea, nausea and vomiting, and alopecia. 

Capecitabine monotherapy See Table 62-1° Diarrhea, hand-foot syndrome... 

CapOx Fluorouradl plus leucovorin only Oxaliplatin 130 mg/m2 day 1 plus capecitabine 850 mg/m2 twice a day for 14 days, repeat every 3 weeks Diarrhea, hand-foot syndrome, neuropathies... 

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. 

Capecitabine Inhibits TS incorporation of FUTP into RNA resulting in alteration in RNA processing incorporation of FdUTP into DNA resulting in inhibition of DNA synthesis and function Breast cancer, colorectal cancer, gastroesophageal cancer, hepatocellular cancer, pancreatic cancer Diarrhea, hand-foot syndrome, myelosuppression, nausea and vomiting... 

FU remains the most widely used agent in the treatment of colorectal cancer, both as adjuvant therapy and for advanced disease. It also has activity against a wide variety of solid tumors, including cancers of the breast, stomach, pancreas, esophagus, liver, head and neck, and anus. Major toxicities include myelosuppression, gastrointestinal toxicity in the form of mucositis and diarrhea, skin toxicity manifested by the hand-foot syndrome, and neurotoxicity. 

Toxicities In addition to nausea, vomiting, diarrhea, and alopecia, severe ulceration of the oral and Gl mucosa, bone marrow depression (with bolus injection), and anorexia are frequently encountered. A dermopathy (erythematous desquamation of the palms and soles) called the hand-foot syndrome is seen after extended infusions. 

Fluorouracil may produce the hand-foot syndrome (known as palmar-plantar erythrodysaesthesia) that results in a dry, reddened and painful area on the extremities of the hands and feet. 

The efficacy and toxicity of Caelyx in combination with paclitaxel (Taxol) were investigated as a first-line therapy in 34 patients with advanced breast cancer in a multicentric phase II study [428], Paclitaxel at a dose of 175 mg/m2 and Caelyx (30 mg/m2) were administered intravenously every 3 weeks. It was shown that the response rates of the combination were over 70% while the median time to treatment failure was 45 weeks. No significant clinical cardiotoxicity was observed and the usual side effects (mucositis, stomatitis, hand-foot syndrome) were treated accordingly. 

Coleman et al. [430] demonstrated that using Caelyx in a dose format of 50mg/m2 every four weeks in patients with metastatic breast cancer is quite effective (objective partial responses 31%) while the main side effect was hand-foot syndrome. 

CALCIUM CHANNEL BLOCKERS DOXORUBICIN t serum concentrations and efficacy of doxorubicin when co-administered with verapamil, nicardipine and possibly diltiazem and nifedipine however, no cases of doxorubicin toxicity have been reported Uncertain however, verapamil is known to inhibit intestinal P-gp, which may t the bioavailability of doxorubicin Watch for symptoms/signs of toxicity (tachycardia, heart failure and hand-foot syndrome)... 

FLUOROURACIL ANTIPROTOZOALS -LEVAMISOLE t risk of hepatotoxicity and neurotoxicity despite t cytotoxic effects Antiphosphatase activity of levamisole may t fluorouracil cytotoxicity This combination has been used successfully in the treatment of colon cancer. Monitor FBC and LFTs regularly. Advise patients to report symptoms such as diarrhoea, numbness and tingling, and peeling of the skin of the hands and feet (hand-foot syndrome)... 

In 60 patients receiving polyethylene glycol-coated liposomal doxorubicin (Doxil) 35-70 mg/m by infusion over 1-2 hours there were four patterns of skin eruption hand-foot syndrome (40%), a diffuse follicular rash (10%), an intertrigo-like eruption (8%), and new melanotic macules (0.5%) (81). 

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