Dacarbazine

Dacarbazine Injection is administered in the treatment of metastatic malignant melanoma. Also, as a second-line therapy, it is prescribed in combination with other drugs to treat Hodgkin's disease.

Generic DTIC-Dome

Dacarbazine

Decarb

1

Cipla Limited

Injection

200 mg

India

Dacarbazine

Introduction

Brief Overview of Dacarbazine

Dacarbazine is a type of medication used in chemotherapy treatments for forms of cancer. It belongs to a group called alkylating agents, which work by modifying the DNA structure, within cancer cells.

Importance in Chemotherapy Regimen

Dacarbazine has shown effectiveness in the treatment of Hodgkins Lymphoma and Malignant Melanoma. Including it in chemotherapy protocols provides benefits, in fighting specific types of cancers.

Scope of the Article

This article explores a range of aspects related to Dacarbazine including its approved and off label applications, pharmacological properties and recommendations, for administration.

Uses of Dacarbazine

Approved Medical Indications

Hodgkin's Lymphoma

Dacarbazine is a chemotherapy drug that is used in the treatment of melanoma and Hodgkin lymphoma1For Hodgkin lymphoma, it is often combined with other chemotherapy drugs, such as doxorubicin, bleomycin, and vinblastine, as part of the ABVD regimen123This regimen is considered the standard of care for patients with advanced-stage Hodgkin lymphoma, as it has shown high cure rates and acceptable toxicity4Dacarbazine damages the DNA of cancer cells, preventing them from dividing and growing1.

1Dacarbazine - Wikipedia 2Doxorubicin, Etoposide, Vinblastine and Dacarbazine (AEVD) for Newly … 3ABVD | Cancer information | Cancer Research UK 4Standard therapy of advanced Hodgkin lymphoma

Malignant Melanoma

Dacarbazine is a chemotherapy drug used to treat melanoma, a type of skin cancer that develops from pigment-producing cells called melanocytes12Dacarbazine can be used alone or with other medications, such as temozolomide, cisplatin, or interferon-alpha, to destroy cancerous melanoma cells13Dacarbazine works by sticking to the DNA of cancer cells and damaging it, which prevents them from dividing and growing.

1Dacarbazine (DTIC) | Melanoma | Cancer Research UK 2Dacarbazine - Wikipedia 3Dacarbazine (DTIC) | Cancer information | Cancer Research UK

Investigational Uses

Dacarbazine is a chemotherapy drug that is used in the treatment of some types of soft tissue sarcoma, which are rare tumors that arise from mesenchymal cells, such as muscle, fat, or connective tissue1Dacarbazine can be used alone or in combination with other drugs, such as doxorubicin, ifosfamide, or gemcitabine, to treat metastatic or unresectable soft tissue sarcoma23Ongoing research is being conducted to evaluate how dacarbazine could be used in treating other types of soft tissue sarcoma, such as angiosarcoma, leiomyosarcoma, or synovial sarcoma13Dacarbazine works by sticking to the DNA of cancer cells and damaging it, which prevents them from dividing and growing2.

1Soft Tissue Sarcoma Treatment (PDQ®) - NCI - National Cancer Institute 2SOFT TISSUE SARCOMA TREATMENT REGIMENS (Part 1 of 2) 3Overview of the initial treatment of metastatic soft tissue sarcoma

Comparative Efficacy to Other Drugs in Similar Cases

Dacarbazine is a chemotherapy drug used for more than 30 years as the standard treatment for advanced metastatic melanoma, a type of skin cancer that develops from pigment-producing cells called melanocytes1Dacarbazine methylates nucleic acids, causing DNA damage resulting in growth arrest and cell death1However, dacarbazine is considered a choice with limited efficacy and high toxicity, and its effectiveness is frequently compared to more recent immunotherapies and targeted treatments in a constantly evolving field of therapy123Immunotherapies are treatments that stimulate the immune system to fight cancer cells, while targeted therapies are treatments that interfere with specific molecules or pathways that are involved in cancer growth or survival23Some examples of immunotherapies and targeted therapies for melanoma are ipilimumab, nivolumab, pembrolizumab, vemurafenib, dabrafenib, and trametinib23.

1Dacarbazine Combined Targeted Therapy versus Dacarbazine Alone … - PLOS 2Frontiers | Dacarbazine-Loaded Targeted Polymeric Nanoparticles for … 3Protocatechuic aldehyde acts synergistically with dacarbazine to …

Off-Label Uses of Dacarbazine

Common Off-Label Applications

Dacarbazine is a chemotherapy drug that is sometimes used to treat neuroendocrine tumors (NETs), which are rare tumors that arise from specialized cells that link the endocrine system (which manages hormones) and the nervous system123Dacarbazine can be used alone or in combination with other drugs, such as ramucirumab, streptozocin, or doxorubicin, to treat NETs that originate from the gastrointestinal tract, such as the pancreas, stomach, or small intestine12However, dacarbazine is not a standard treatment for NETs and there have been reports of effectiveness based on anecdotal evidence or small studies12More research is needed to evaluate the efficacy and safety of dacarbazine for NETs and to compare it with other treatment options12.

1Ramucirumab in combination with dacarbazine in patients with … 2Metastatic well-differentiated gastrointestinal neuroendocrine … 3Gastrointestinal Neuroendocrine Tumors (GI NET) - Cleveland Clinic

Research and Studies Supporting Off-Label Uses

The use of Dacarbazine in scenarios that go beyond its FDA-approved indications is being documented more and more in the literature, although there isn't a universal consensus, on this.

Ethical Considerations in Off-Label Use

When doctors consider using a medication for a purpose other than its approved use, they need to carefully balance the available evidence, with the possible risks. They should also follow the principles of ethics.

How Dacarbazine Works

Mechanism of Action at the Cellular Level

Dacarbazine is a type of medication that works by attaching itself to the N7 position of guanine which in turn prevents the replication of DNA and the transcription of RNA.

Pharmacodynamics and Pharmacokinetics

After it is given Dacarbazine is quickly processed by the liver. It usually takes around 40 to 75 minutes for its effects to decrease by half.

The Role of Dacarbazine in DNA Damage

Dacarbazine works by creating damage, in the DNA leading to the death of cells. This disrupts the pathways that promote tumor growth and ultimately causes apoptosis.

Composition of Dacarbazine

Active Ingredients

Dacarbazine itself is the component usually found in the form of a sterile powder.

Inactive Ingredients and Excipients

The formulation typically contains active ingredients such, as mannitol and sodium chloride to ensure it stays isotonic.

Available Formulations (Injectable, etc.)

Dacarbazine is primarily found in a form that needs to be mixed before it can be given through an injection, into a vein.

Dosage and Administration

Standard Dosage Guidelines

The recommended dose usually falls within the range of 150 to 375 mg/m² depending on the chemotherapy regimen being used.

Route of Administration

Dosage Modifications in Specific Populations

Renal Impairment

Hepatic Impairment

Common Side Effects of Dacarbazine

Gastrointestinal Issues

Hematological Effects

Dermatological Reactions

Frequency and Severity of Side Effects

VIII. Less Common but Serious Side Effects

Neurological Complications

Cardiovascular Issues

Risk of Secondary Malignancies

IX. Drug Interactions with Dacarbazine

Common Drugs that Interact

Effect on Cytochrome P450 Enzymes

Impact on Efficacy of Concomitant Medications

X. Warnings and Contraindications

Absolute Contraindications

Relative Contraindications

Required Medical Tests Before Initiation

XI. Careful Administration and Important Precautions

Monitoring Parameters

Preventive Measures for Side Effects

Management of Toxicities

XII. Special Populations

Administration to Elderly

Age-related Dosage Adjustments

Geriatric Concerns

Administration to Pregnant Women and Nursing Mothers

Fetal Risks

Lactation Warnings

Administration to Children

Pediatric Dose Recommendations

Efficacy and Safety in Children

XIII. Overdosage and Management

Symptoms of Overdosage

Immediate Management Steps

Antidotes if Available

XIV. Storage Guidelines for Dacarbazine

Temperature Requirements

Light Sensitivity

Shelf-life Considerations

XV. Handling Precautions

Personal Protective Equipment for Healthcare Providers

Safe Disposal Methods

Contamination Risks and Mitigation

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