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Table 2 Pharmacokinetics and adverse effects of chemotherapeutic drugs for the therapeutic management of various types of skin cancer

From: Skin cancer therapeutics: nano-drug delivery vectors—present and beyond

Chemotherapeutic agent

Dosage regimen

Adverse effects



Imiquimod (5%)

Superficial BCC- 5 times in a week for 6 weeks

Actinic keratosis: 2 times in a week for 16 weeks

Cutaneous erythema, swelling, erosions, crusts, vesicles, pruritis, and, occasionally, tingling sensations. Systemic symptoms include fatigue, influenza-like symptoms, myalgia, and headache

Mean peak serum concentration was found to be 0.1, 0.2, and 3.5 ng/mL at for 12.5, 25 and 75 mg at the end of 16 weeks This indicates minimal systemic absorption and prolonged retention of drug in the skin


5 Fluorouracil

Actinic keratosis- 0.5% once a day for 2–4 weeks

BCC: 5% cream twice a day for 3–6 or 10–12 weeks

Erythema, swelling, crust, erosions, ulcers, and eschar

0.5% cream shows minimal systemic absorption



Metastatic BCC or locally advanced BCC 150 mg orally once daily

Muscle spasms and arthralgias, alopecia, and dysgeusia often culminating in weight loss. It is embryotoxic and teratogenic

Bioavailability is 31.8%, serum protein binding observed was higher than 99%, half-life is 4 days. It is well distributed in the body

[41, 42]

Ingenol mebutate

Ak of face and scalp-0.015% once daily for 3 consecutive days

AK of trunks and extremities- 0.05% once daily for 2 consecutive day

Local skin reactions like pain, pruritis, infection, periorbital edema, nasopharyngitis and headache

0.05% gel shows minimal systemic absorption


Dicolfenac (3%)

AK- Twice daily topically for 60–90 days

Localized dermal side effects such as contact dermatitis, exfoliation, dry skin, and rash

Systemic bioavailability after topical application is lower than that after oral administration, approximately 10% gets absorbed after topical application, gets associated to serum albumin, half-life being 1–2 h



SCC- 400 mg/m2 by infusion administered one week prior to radiation therapy or on the day of initiation of other chemotherapeutic agent. Subsequent dose is 250 mg/m2 by infusion weekly for 6–7 weeks

Cutaneous side effects including rash, itching, and nail changes, headache, diarrhea, and infection

It follows non-linear pharmacokinetics, is mainly restricted to the intravascular compartment. It reaches steady state by the third week and has a plasma half-life of 112 h. It has a poor distribution within hypoxic regions of the tumor

[45, 46]


Malignant melanoma- 2 to 4.5 mg/kg/day orally for 10 days. Treatment may be repeated at 4 week intervals

OR 250 mg/square meter body surface/day I.V. for 5 days. Treatment may be repeated every 3 weeks

Symptoms of anorexia, nausea, and vomiting

After administration the volume of distribution exceeds total body water content indicating partial distribution in tissue, mostly the liver. It has a terminal half-life of 5 h



Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation- 450 mg orally once daily in combination with Binimetinib

Fatigue, nausea, vomiting, abdominal pain, and arthralgia

At least 86% of the dose is absorbed and a similar percentage is associated to plasma proteins, with an apparent volume of distribution of 164 L, the terminal half-life -3.5 h, is extensively distributed in the tissues highest levels are found in the liver

[51, 52]


Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation- 960 mg orally twice daily taken approximately 12 h apart

Arthralgia, rash, alopecia, fatigue, photosensitivity reaction, nausea, itching, and skin papilloma

Bioavailability data is not yet available. Highly protein bound (more than 99%) with a volume of distribution of 106 L, elimination half-life is 57 h. Non clinical data reports that this drug is equally distributed in tissue and blood, however it doesn’t penetrate brain and spinal cord



Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation- 150 mg orally twice daily as a single agent or in combination with trametinib, at least 1 h before or at least 2 h after a meal

Hyperkeratosis, headache, pyrexia, arthralgia, papilloma, alopecia, and palmar-plantar erythrodysesthesia syndrome

Bioavailability is 95%, 99.7% is bound to plasma proteins with a volume of distribution of 70.3L. The metabolites-hydroxy- and desmethyl-dabrafenib are likely to contribute to the clinical activity of Dabrafenib. Terminal half-life is 8 h. It exhibits a widespread tissue distribution

[54, 55]


Unresectable or metastatic melanoma

 3 mg/kg intravenously over 90 min every 3 weeks for a total of 4 doses

Adjuvant melanoma: 10 mg/kg intravenously over 90 min every 3 weeks for 4 doses, followed by 10 mg/kg every 12 weeks for up to 3 years

Fatigue, diarrhea, itching, rash, and colitis. nausea, vomiting, headache, weight loss, pyrexia, anorexia and insomnia

It follows linear pharmacokinetics, steady state concentration is achieved after the 3rd dose, terminal half-life is 15.4 days. It remains in the vasculature and doesn’t undergo tissue distribution

[56, 57]


Unresectable or metastatic melanoma 240 mg every 2 weeks or 480 mg every 4 weeks. OR 1 mg/kg, followed by Ipilimumab on the same day, every 3 weeks for 4 doses, then Nivolmab 240 mg every 2 weeks or 480 mg every 4 weeks

Adjuvant treatment of melanoma 240 mg every 2 weeks or 480 mg every 4 weeks

Fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, anorexia, back pain, arthralgia, upper respiratory tract infection, pyrexia, headache, abdominal pain, and vomiting

Steady state concentration is achieved after 12 weeks, half-life is 25 days. Owing to high molecular mass, it is very slowly distributed in the tissue and is bound to the antigens present in the tissue or in blood

[58, 59]


Melanoma or head neck SCC: 200 mg as intravenous infusion every 3 weeks

Fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain

Steady-state concentrations of Pembrolizumab are reached by 16 weeks, terminal half-life is 22 days. Preclinical data reports that Pembrolizumab accumulates in liver and spleen tissue

[60, 61]


Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation- 2 mg orally once daily as a single agent or in combination with Dabrafenib, at least 1 h before or at least 2 h after a meal

Rash, diarrhea, and lymphedema

Absolute bioavailability is 72%, 97.4% is bound to plasma proteins and apparent volume of distribution is 214L, half-life is 3.9–4.8 days. It is widely distributed in the tissues; however penetration in the brain is low. It also exhibited accumulation in the pigmented skin

[54, 55]


Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation- 60 mg orally once daily for the first 21 days of each 28-day cycle until disease progression

Diarrhea, photosensitivity reaction, nausea, pyrexia, and vomiting

The absolute bioavailability is 46%, 95% is bound to plasma proteins. It preferentially binds to red blood cells and has volume of distribution of 806 L, elimination half- life is 44 h. Preclinical studies indicate wide distribution of the drug after oral administration, it is found more in the lacrimal glands and pigmented skin and very less in the CNS

[62, 63]

NRAS Inhibitors—Binimetinib

Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation- 45 mg orally twice daily in combination with Encorafenib

In combination with Encorafenib, it causes fatigue, nausea, diarrhea, vomiting, and abdominal pain

50% of the dose is absorbed, 97% is bound to plasma proteins with a volume of distribution of 92 l, half-life is 3.5 h. It is widely distributed in the tissue, however very less permeates in the CNS

[64, 65]

Talimogene laherparepvec

Local treatment of unresectable cutaneous- subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery- starting dose is up to a maximum of 4 mL at a concentration of 106 (1 million) plaque-forming units (PFU) per mL. Subsequent doses should be administered up to 4 mL at a concentration of 108 (100 million) PFU per mL (3 and /or 5 weeks after initial treatment)

Fatigue, chills, pyrexia, nausea, influenza-like illness, and injection site pain, herpetic infection, immune mediated events, risk of spread to people in close contact with the patient following administration

85% of the DNA is found in blood and 20% in urine