Chemotherapeutic Agents

Docetaxel is a widely used chempotherapeutic agent in treatment of various malignancies like hormone refractory prostate cancer. There are many side effects due to the docetaxel. Despite the other side effects, cutanous manifestations are affecting the patient's quality of life.
Case
A 65 year old man diagnosed with T4N1M1 prostate adenocarcinoma was treated with bicalutamide 150 mg oral daily and gosereline 10,8 mg subcutaneously every three months for nine months. He began to receive second line chemotherapy with intravenous docetaxel and estramustine for hormone refractory disease. On 7th day of cycle 4, patient presented with hyperpigmentation of skull, both hands, left axillar area, neck and both feet. Chemotherapy protocol was stopped and the patient treated with hydrocortisone 1% cream. He also advised to apply cold compress three times a day to the reaction sites. All lesions recovered at the 5th week of the treatment. Conclusion
Even the cutaneous side effects of the docetaxel are not life threatening, it must be kept in mind by the urologists and oncologists for the sake of the chemotherapy in patients with advanced cancer.

Introduction
Chemotherapeutic agents are widely used in treatment of various malignancies may be associated with various cutaneous adverse effects like hyper sensitivity and neutropenia (1). Hyperpigmented linear streaks following the superficial venous network at the injection site have been frequently reported after administration of several chemotherapeutics (2). Docetaxel belongs to the taxane class of chemotherapeutic drugs and acts by disrupting the micro tubular network in cells. Stabilization of microtubules results in the inhibition of mitosis (3).

The combination of docetaxel with other chemotherapeutics is approved for the treatment of metastatic, androgen-independent (hormone-refractory) prostate cancer, adjuvant treatment of operable node-positive breast cancer, advanced gastric adenocarcinoma, metastatic non-small cell lung cancer, and also in inoperable, locally advanced squamous cell carcinoma of the head and neck (4).

Even there are many systemic side effects of docetaxel, discrete erythematous or edematous plaques similar to acral erythema can be seen as cutaneous manifestations and usually occur 2'4 days after treatment(2).

Despite well-known local cutaneous side effects of docetaxel, we present a case of cutaneous lesions widely spread at different sites of body beside the injection side due to the docetaxel.

Case Report

A 65 year old Azerbaijani man diagnosed with T4N1M1 prostate adenocarcinoma in January 2012. He was treated with bicalutamide 150 mg oral daily and gosereline 10,8 mg subcutaneously every three months for nine months. After nine month he began to receive second line chemotherapy with intravenous infusions of three-weekly docetaxel 75 mg/m2 and twice a day estramustine 30 mg /m2 for hormone refractory disease. He completed 3 cycles of chemotherapy. On 7th day of cycle 4, patient presented with hyperpigmentation of skull, both hands, left axillar area, neck and both feet (Figure 1). He had no complaint of pain at the affected areas. Chemotherapy protocol was stopped and the patient treated with hydrocortisone 1% cream via consulting to the dermatology. He also advised to apply cold compress three times a day to the reaction sites. All lesions recovered at the 5th week of the treatment.
Discussion
Docetaxel is a chemotherapeutic agent from the taxane group and has been used as a second-line treatment following unsuccessful therapy of various cancers including hormone refractory prostate cancer (3). Docetaxel inhibits the mitosis in tumour cells by attaching the free tubulin in the tumour cells and giving rise to accumulation and stabilization of tubulin in microtubules (5).

Docetaxel based chemoteraphy has been widely used for many advanced cancers like hormone refractory prostate cancer as well(6). Cutaneous side effect of docetaxel does not life threatening, but it can negatively affect the quality of life of patients. Docetaxel induced cutaneous toxicity has also been described as a risk factor for major infections in a randomized controlled trial involving metastatic breast cancer patients treated with docetaxel(7). The etiology of cutaneous reactions from systemic administration of docetaxel is unknown. It can be a direct toxic effect of docetaxel. Frequent adverse events include dose-dependent neutropenia, hypersensitivity, fluid retention, skin and nail reactions, asthenia, alopecia, nausea, vomiting, diarrhea, mucositis, sensory neuropathies, arthralgia and myalgia (1).

Extravasation of docetaxel can also cause erythema, edema, blistering, desquamation, dermatitis resulting in skin discoloration, and hyperplasia at the injection site. Chu et al. describes four patients with fixed erythrodysaesthesia plaque following administration of weekly docetaxel infused over 30 min. Our reports differ from the other with eruptions with spread to the different sites of body except the injection site. Also hyperpigmentation occurred after the 4th cycle of the docetaxel immediately in one night. Hyperpigmentation sites were left side of skull, dorsum of both hands, left axillar area, neck and anterior region of both feet.
The management strategies of cutaneous reactions include hand elevation, warm or cold compresses, topical and/or systemic corticosteroids, and cessation of drug (3). We stopped the chemotheraphy and treated the lesions with hydrocortisone 1% cream and cold compress to the lesions three times a day due to the advice of dermatology for 5 weeks. After 5 weeks all hyperpigmentation disappeared.

Conclusion
It is obvious that the side-effects of this chemotherapeutic agent will increase in future due to the increase in cancer. Patients receiving docetaxel should be informed of the various cutaneous reactions that can occur receiving or following chemotherapy.

Source: Essay UK - http://www.essay.uk.com/free-essays/science/chemotherapeutic-agents.php



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