How Do Other Antineoplastics Work?

Antineoplastics are medications that prevent, inhibit, or halt the growth of neoplasms (tumors), used to treat various types of cancers. Medications that do not fall into any specific class of antineoplastics are categorized as other antineoplastics. Other antineoplastics include the following medications each of which works in unique ways:

• Arsenic trioxide: Arsenic trioxide is an antineoplastic drug used to treat acute promyelocytic leukemia (APL), an aggressive type of cancer with excessive immature white blood cells in blood and bone marrow. APL is characterized by a chromosomal translocation that fuses promyelocytic leukemia (PML) gene and retinoic acid receptor-alpha (RAR-A) gene, which results in the production of PML-RAR alpha fusion protein.
  • The abnormal fusion protein blocks the maturation and differentiation of white cells leading to the proliferation of immature cells. Arsenic trioxide causes structural changes and fragmentation of the cancer cell DNA, inducing programmed cell death (apoptosis) in the cancer cells, and also damages and degrades the PML-RAR fusion protein.
• Eflornithine/sulindac: Eflornithine/sulindac is a combination drug being developed (pending FDA approval) to delay the need for surgeries in familial adenomatous polyposis (FAP), an inherited disorder that causes the growth of multiple precancerous polyps in the colon and rectum.
  • Eflornithine inhibits ornithine decarboxylase (ODC), an enzyme that catalyzes the synthesis of compounds required for cell division and differentiation. Sulindac, a nonsteroidal anti-inflammatory drug (NSAID) causes cell death by blocking cyclic guanosine monophosphate-phosphodiesterase (cGMP-PDE), an enzyme that inhibits cell apoptosis.
• Inotuzumab: Inotuzumab ozogamicin is an antibody-drug conjugate used to treat B-cell precursor acute lymphoblastic leukemia, a type of blood cancer. Inotuzumab ozogamicin is a conjugate of a lab-made antibody against human CD22, N-acetyl-gamma-calicheamicin, a cytotoxin, and a substance that links the two drugs.
  • The antibody component of the drug recognizes and specifically binds to CD22, a protein found on B-cell membranes, and the cytotoxin calicheamicin enters into the B-cell and causes double-strand DNA breaks inducing cell cycle arrest and apoptotic cell death.
• Larotrectinib: Larotrectinib is used to treat metastatic solid tumors that have neurotrophic tyrosine receptor kinase (NTRK) gene fusion. NTRK genes encode proteins known as tropomyosin receptor kinases (TRK), and larotrectinib prevents tumor growth by inhibiting the drivers of tumor growth, the abnormal TRK proteins resulting from NTRK gene fusion.
• Mitotane: Mitotane is an antineoplastic used to treat inoperable adrenocortical carcinoma, cancer that affects the adrenal cortex, the outer region of the adrenal gland. Mitotane is cytotoxic to adrenal tissue and suppresses the adrenal cortex, leading to adrenal atrophy and tumor death.
• Polatuzumab vedotin: Polatuzumab vedotin is an antibody-drug conjugate used to treat diffuse large B-cell lymphoma, a type of lymphatic cancer. Polatuzumab vedotin is a conjugate of humanized immunoglobulin G1 (IgG1) monoclonal antibody against CD79b, a B-cell protein, monomethyl auristatin E (MMAE), and an agent that links them.
  • The monoclonal antibody identifies and binds to CD79b, a B-cell-specific surface protein, and delivers MMAE into the B-cell. MMAE is an anti-mitotic agent that kills dividing B-cells by inhibiting cell division and inducing apoptosis.
• Porfimer: Porfimer is a photosensitizing agent used in photodynamic therapy (PDT) for tumors and growths that affect the esophagus. Porfimer is injected intravenously and is activated with 630 nm wavelength laser light precisely focused on the tumor, after 40-50 hours.
  • Exposure to laser light activates porfimer retained in the tumor, which produces oxygen free radicals, destroying the tumor cells. The light-activated porfimer also causes the release of thromboxane A2, a substance made by platelets that causes blood clotting, which occludes the blood vessels in the tumor and blocks its blood supply.
• Tagraxofusp: Tagraxofusp is an antineoplastic used to treat blastic plasmacytoid dendritic cell neoplasm (BPDCN), a cancer of dendritic cells, a type of immune cells. Tagraxofusp is a fusion protein composed of recombinant human interleukin-3 and truncated diphtheria toxin.
  • Human interleukin-3 is a growth factor that induces the proliferation and differentiation of blood cells and immune cells by binding to CD123, a receptor that these cells express. Tagraxofusp identifies and binds to CD123, prevents protein synthesis, and causes cell death.
• Tumor necrosis factor-alpha (TNF-A) adenovector: Tumor necrosis factor-alpha (TNF-A) adenovector is a medication being investigated for use in pancreatic, head and neck, esophageal and rectal cancers. TNF-A is an immune system protein with potent anticancer effects.
  • TNF-A adenovector is a harmless adenovirus genetically engineered to carry the gene for TNF-A protein in its DNA. The medication is directly injected into solid tumors, the TNF-A gets inserted into the DNA of tumor cells and exerts its effects.

Other antineoplastics may be administered through the following routes:

• Oral:
  • Capsules
  • Tablets
  • Solutions
• Injections:
  • Intravenous (IV) injections or infusions into the vein
  • Intratumoral injections into the tumor

Uses of other antineoplastics include:

• Arsenic trioxide:
  • Treatment of newly diagnosed or relapsed/refractory acute promyelocytic leukemia with t (15;17) translocation or PML/RAR alpha gene expression, in combination with tretinoin
  • Orphan indications include:
    • Chronic lymphocytic leukemia
    • Malignant glioma
    • Myelodysplastic syndrome
    • Multiple myeloma
    • Liver cancer
    • Chronic myeloid leukemia
    • Amyotrophic lateral sclerosis
    • Graft-versus-host disease
• Eflornithine/sulindac:
  • To delay the need for major surgeries in the colon and rectum due to familial adenomatous polyposis (FAP), an inherited disorder marked by growth of multiple precancerous polyps in the colon/rectum and a high risk of colorectal cancer
• Inotuzumab:
  • Treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia, a blood cancer with too many B-cell lymphoblasts (premature lymphocytes)
• Larotrectinib:
  • Treatment of patients with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no alternative treatments or have progressed following treatment
• Mitotane:
  • Inoperable, functional, or non-functional adrenal cortical carcinoma, a cancer of the adrenal gland, which causes the production of too much hormone (functional) or too little (non-functional)
  • Cushing’s syndrome is an adrenal gland disorder that causes the production of excessive cortisol hormone
• Polatuzumab vedotin:
  • Treatment of relapsed or refractory diffuse large B-cell lymphoma (a cancer of the lymphatic system) after 2 or more prior therapies, in combination with bendamustine and rituximab
• Porfimer:
  • Palliative treatment for patients with completely obstructing esophageal cancer
  • Treatment of microinvasive endobronchial non-small cell lung cancer (NSCLC) when surgery and radiotherapy are not possible
  • Ablation of high-grade dysplasia (growth of abnormal cells) in Barret’s esophagus, a complication from gastrointestinal reflux disease (GERD)
  • Orphan indications include:
    • Bladder carcinoma
    • Cholangiocarcinoma (bile duct cancer)
    • Mesothelioma, is a cancer of the thin tissue (mesothelium) that lines the lungs, chest wall, and stomach
• Tagraxofusp:
  • Blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare fast-growing cancer that affects the blood, bone marrow, and skin
• Tumor necrosis factor-alpha (TNF-A) adenovector:
  • Investigational/orphan status for:
    • Pancreatic cancer
    • Head and neck cancer
    • Esophageal cancer
    • Rectal cancer

Side effects of other antineoplastics vary with each drug. A few of the most common side effects may include:

• Arsenic trioxide:
  • Nausea and vomiting
  • Cough
  • Fatigue
  • Pyrexia (fever)
  • Headache
  • Abdominal pain, diarrhea
  • Tachycardia (rapid heartbeat)
  • Dyspnea (shortness of breath)
  • Leukocytosis (high level of white blood cells, leukocytes)
  • Pain, including back pain, bone pain, and myalgia (muscle pain)
  • Hypokalemia, hypomagnesemia (drop in potassium and magnesium levels)
  • Hyperglycemia (high blood glucose levels)
• Eflornithine/sulindac:
  • Nausea and vomiting
  • Diarrhea
  • Abdominal pain
  • Rectal hemorrhage
  • Blood in stool
  • Gastroenteritis
  • Ear and labyrinth disorders
  • Upper respiratory tract infection
  • Headache
  • Rash
• Inotuzumab:
  • Thrombocytopenia (low count of platelets in the blood)
  • Neutropenia (low count of neutrophils, type of immune cells)
  • Leukopenia (low count of leukocytes)
  • Anemia (low red blood cells)
  • Infection
  • Fatigue
  • Hemorrhage
  • Pyrexia (fever)
  • Nausea and vomiting
  • Headache
  • Elevated liver enzymes
• Larotrectinib:
  • Increased liver enzymes AST and ALT
  • Anemia
  • Fatigue
  • Hypoalbuminemia (low albumin level in the blood)
  • Increase in alkaline phosphatase
  • Nausea and vomiting
  • Cough
  • Neutropenia
  • Constipation
  • Diarrhea
• Mitotane:
  • Nausea and vomiting
  • Lethargy and somnolence (drowsiness)
  • Anorexia (loss of appetite)
  • Vertigo
  • Skin rash
  • Diarrhea
  • Weakness
• Polatuzumab vedotin:
  • Decreased lymphocyte count
  • Increase in creatinine
  • Decrease in neutrophil
  • Decrease in hemoglobin
  • Decrease in platelets
  • Anemia
  • Decrease in calcium levels
  • Peripheral neuropathy
  • Diarrhea
  • Elevated liver enzymes ALT and AST
• Porfimer:
  • Anemia
  • Fever
  • Pleural effusion
  • Constipation
  • Chest pain
  • Abdominal pain
  • Dyspnea
  • Pneumonia
  • Insomnia
  • Back pain
• Tagraxofusp:
  • Increase in glucose levels
  • An increase in liver enzymes ALT and AST
  • Decrease in albumin
  • Decrease in platelets
  • Decrease in hemoglobin
  • Decrease in calcium, sodium levels
  • Nausea and vomiting
  • Capillary leak syndrome
  • Peripheral edema
  • Pyrexia (fever) and fatigue
• Tumor necrosis factor-alpha (TNF-A) adenovector:
  • Fever
  • Injection site pain
  • Chills

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these products do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of some of the other antineoplastics include:

• arsenic trioxide
• Besponsa
• eflornithine/sulindac (pending FDA approval)
• Elzonris
• inotuzumab
• larotrectinib
• Lysodren
• mitotane
• Photofrin
• polatuzumab vedotin
• polatuzumab vedotin-piiq
• Polivy
• porfimer
• tagraxofusp
• tagraxofusp-erzs
• TNFerade
• Trisenox
• tumor necrosis factor-alpha (TNF-alpha) adenovector
• Vitrakvi