Palmar-plantar erythrodysesthesia

Capedtabine is the prodrug of 5-FU and comes as oral tablets that are administered with food twice a day. Capedtabine has shown to be active in tumors of the colon, rectum, and breast. The toxicity profile of capecitabine is similar to that of 5-FU and includes diarrhea, mucositis, palmar-plantar erythrodysesthesia,... 

Liposomal doxorubicin is an irritant, not a vesicant, and is dosed differently from doxorubicin, so clinicians need to be very careful when prescribing these two drugs. The pharmacokinetics of liposomal doxorubicin are best described by a two-compartment model, with a terminal half-life of 30 to 90 hours.20 Liposomal doxorubicin has shown significant activity in the treatment of breast and ovarian cancer, along with multiple myeloma and Kaposi s sarcoma. Side effects include mucositis, myelosuppression, alopecia, and palmar-plantar erythrodysesthesia. The liposomal doxorubicin may be less cardiotoxic than doxorubicin. 

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

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. 

There has been a report of six cases of a variant of the palmar-plantar erythrodysesthesia syndrome (hand-foot syndrome), in which patients who had previously reported the syndrome developed it again when they were treated with completely different chemotherapeutic drugs (57). The recall syndrome was of mild to moderate intensity, less severe than the primary syndrome, and self-limiting in all cases. 

With protracted continuous infusion of 200-400 mg/m / day, mucositis and palmar-plantar erythrodysesthesia syndrome are the most common dose-limiting adverse effects (2). 

Some very high-dose, short-exposure studies have been reported, including 14 g over 24 hours (3) and 2.6 g/m weekly (4) in the latter study, neurotoxicity was dose-limiting with 24-hour infusion of 2.6 g/m weekly, palmar-plantar erythrodysesthesia syndrome is a major adverse effect. 

The dose and duration of protracted infusional fluorouracil is hmited by mucositis, diarrhea, and/or palmar-plantar erythrodysesthesia. Typically, palmar-plantar dysesthesia begins several weeks to months after starting treatment. Although the dysesthesia abates within several weeks of discontinuing the infusion, it rapidly recurs when the infusion is resumed. Five patients who developed palmar-plantar dysesthesia during infusion of fluorouracil were treated with oral pyridoxine, 50 or 150 mg/day, once it reached moderate severity (149). The severity of the skin toxicity improved, with resolution of pain in four of the five patients, despite continued administration of fluorouracil. The abihty of pyridoxine to modulate fluorouracil-induced cutaneous toxicity is currently undergoing evaluation in the randomized trial (150). 

BeUmunt J, Navarro M, Hidalgo R, Sole LA. Palmar-plantar erythrodysesthesia syndrome associated with short-term continuous infusion (5 days) of 5-fluorouracil. Tumori 1988 74(3) 329-31. 

Vukelja SJ, Lombardo FA, James WD, Weiss RB. Pyridoxine for the palmar-plantar erythrodysesthesia syndrome. Ann Intern Med 1989 lll(8) 688-9. 

Molina R, Fabian C, Slavik M, et al. Reversal of palmar-plantar erythrodysesthesia SPPE by B6 without loss of response in colon cancer patients receiving 200 mg/m / day continuous 5-FU. Proc Am Soc Clin Oncol 1987 6 90. 

The toxicity of antimetabolites is, as expected, due to their incorporation into the metabolism of normal cells, which is nearly identical to that of the malignant cells that they were designed to injure. The normal cells injured most severely are the rapidly proliferating cells of the bone marrow, the lymphoid system, and the GI epithelium. Thus, the common toxicities are bone marrow depression, nausea and vomiting, diarrhea, and mucositis. Cytarabine and pentostatin can cause conjunctivitis. Capecitabine and prolonged use of fluorouracil or cytarabine can cause cerebellar ataxia and the hand-foot syndrome, that is, palmar-plantar erythrodysesthesia or acral erythema. Pentostatin and high-dose methotrexate can cause renal toxicity. 

Palmar-plantar erythrodysesthesia (hand-foot syndrome) diarrhea stomatitis dermatitis bone marrow depression hyperbilirubinemia ocular irritation and corneal deposits... 

Oral and Gl ulcers bone marrow depression diarrhea (especially with fluorouracil and leucovorin) neurological defects, usually cerebeller cardiac arrhythmias angina pectoris alopecia hyperpigmentation palmar-plantar erythrodysesthesia conjunctivitis heart failure seizures... 

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. 

Palmar-plantar erythrodysesthesia syndrome (commonly called hand-foot syndrome) has been reported to be associated with docetaxel, although various patterns of spread, from solitary erythematous plaques to widespread involvement of the trunk, have been observed [139, 140 ]. 

Ko EM, Lippmann Q, Caron WP, Zamboni W, Gehrig PA. Clinical risk factors of PEGylated liposomal doxorubicin induced palmar plantar erythrodysesthesia in recurrent ovarian cancer patients. Gynecol Oncol 2013 131(3) 683-8. 

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