carboplatin

Carboplatin is a chemotherapy medication used in the treatment of advanced ovarian cancer as a single agent or in combination with other approved chemotherapy drugs.

Carboplatin used in combination with cyclophosphamide is an established regimen of chemotherapy. Carboplatin is a platinum-based alkylating antineoplastic drug derived from another anticancer drug cisplatin, with reduced side effects of vomiting and kidney toxicity.

Carboplatin enters into the cancer cells, binds to the DNA and forms cross-links between the DNA strands. This modifies the DNA structure and prevents the DNA strands from separating for transcription into RNA, and synthesis of RNA and DNA, controlling the growth and proliferation of cancer cells. Carboplatin appears to exert its effects in all phases of cell cycle.

What cancers are treated with carboplatin?

Carboplatin is used in the treatment of several cancers, mostly advanced, recurrent, or metastatic, including the following:

FDA-approved:

• Initial treatment of advanced ovarian carcinoma
• Palliative treatment of ovarian carcinoma that is recurrent after prior chemotherapy

Off-label uses:

• Advanced anal cancer
• Bladder cancer
• Advanced or metastatic breast cancer
• Recurrent or metastatic cervical cancer
• Advanced or recurrent endometrial cancer
• Esophageal cancer
• Gastric cancer
• High-risk, refractory gestational trophoblastic neoplasia
• Head and neck cancer
• Hematopoietic stem cell transplant for metastatic germ cell tumors
• Relapsed or refractory Hodgkin lymphoma
• Malignant pleural mesothelioma
• Advanced or metastatic melanoma
• Merkel cell carcinoma
• Advanced, atypical or poorly differentiated, neuroendocrine tumors (nonpulmonary)
• Relapsed or refractory non-Hodgkin lymphomas
• Small cell lung cancer
• Non–small cell lung cancer
• Castration-resistant, metastatic prostate cancer
• Sarcomas including Ewing sarcoma and osteosarcoma
• Testicular cancer
• Advanced thymoma or thymic malignancies
• Anaplastic thyroid carcinoma
• Unknown primary cancer

• Do not use carboplatin in patients with a history of severe allergic reactions to carboplatin, other platinum containing compounds or any of the components in the formulation.
• Do not administer carboplatin to patients with severe bone marrow depression or significant bleeding.
• Do not administer carboplatin to pregnant or breastfeeding women. Advise women of pregnancy potential to use effective contraception. If a patient becomes pregnant while on carboplatin treatment, apprise the patient of the potential hazard to the fetus.
• Carboplatin should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents, in an establishment where adequate treatment facilities are readily available for the appropriate management of therapy and any complications that arise.
• There may be severe dose-related bone marrow depression that can result in infection and/or bleeding.
  • Blood count should be frequently monitored during treatment.
  • Anemia may be cumulative and may require transfusion, particularly with prolonged treatment.
• The risk of bone marrow suppression is higher in patients who have received prior therapy, especially regimens that include cisplatin, and patients with impaired kidney function. Initial dosages should be appropriately reduced in these patients and blood counts should be closely monitored between courses of carboplatin.
• Vomiting is a frequent side effect of carboplatin treatment, which may require premedication with antiemetics.
• There have been reports of severe allergic (anaphylactic-like) reactions to carboplatin that have occurred within minutes of carboplatin administration. The risk is higher in patients who have previously received platinum therapy. Epinephrine, corticosteroids, and antihistamines have been employed to alleviate symptoms.
• High doses of carboplatin have resulted in severely abnormal liver function tests.
• Carboplatin has limited nephrotoxicity, but concurrent use with aminoglycoside antibiotics can increase the risk of kidney toxicity, exercise caution.
• Higher than recommended doses and concurrent use of carboplatin with other drugs that are toxic to the ear (ototoxic) have resulted in hearing loss in pediatric patients. Use with caution.
• The risk of peripheral neurotoxicity from carboplatin, although infrequent, is higher in patients older than 65 years of age and in those previously treated with cisplatin.
• Use of higher than recommended doses of carboplatin has been reported to result in vision loss, which can be complete for light and colors. Vision appears to recover totally or to a significant extent within weeks after stopping high doses.
• Needles or intravenous administration sets containing aluminum parts that may come in contact with carboplatin Injection should not be used for preparation or administration of the drug. Aluminum can react with carboplatin causing precipitate formation and loss of potency.

Common side effects of carboplatin include:

• Nausea
• Vomiting
• Gastrointestinal pain
• Constipation
• Diarrhea
• Oral inflammation (stomatitis)
• Inflammation of mucous membranes (mucositis)
• Bone marrow depression including:
  • Low red blood cell count (anemia)
  • Low platelet count (thrombocytopenia)
  • Low count of neutrophil immune cells (neutropenia)
  • Low count of leukocyte immune cells (leukopenia)
• Bleeding
• Transfusions
• Infections
• Pain
• Weakness (asthenia)
• Central neurotoxicity
• Peripheral nerve disease (neuropathy)
• Toxicity to the ear (ototoxicity)
• Visual disturbance
• Taste perversion (dysgeusia)
• Increase in serum alkaline phosphatase
• Increase in liver enzyme aspartate aminotransferase (AST/SGOT)
• Elevation of bilirubin levels
• Loss of electrolytes including:
  • Magnesium
  • Calcium
  • Potassium
  • Sodium
• Reduced creatinine clearance
• Increase in serum creatinine
• Increase in blood urea nitrogen (BUN)
• Hair loss (alopecia)
• Hypersensitivity reactions including:
  • Rash
  • Hives (urticaria)
  • Itching (pruritus)
  • Redness (erythema)

Less common side effects of carboplatin include:

• Loss of appetite (anorexia)
• Neutropenia with fever (febrile neutropenia)
• Damage to small blood vessels in kidney (hemolytic-uremic syndrome)
• Inflammation in the kidney (acute interstitial nephritis)
• Dehydration
• High blood pressure (hypertension)
• Hypersensitivity reactions including:
  • Bronchospasm
  • Low blood pressure (hypotension)
  • Severe allergic reaction (anaphylaxis)
• Feeling unwell (malaise)
• Injection site reactions including:
  • Pain
  • Swelling
  • Redness (erythema)
• Optic disc swelling and bleeding due to high intracranial pressure (hemorrhagic papilledema)
• Respiratory effects
• Genitourinary effects
• Cardiovascular effects including:
  • Cardiac failure
  • Blood clot block (embolism)
• Cerebrovascular accident

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Lyophilized Powder for Reconstitution

• 150 mg

Injectable Solution

• 10 mg/mL (in vials of 50, 150, 450, and 600 mg)

Adult:

Advanced Ovarian Carcinoma

• Single agent: 360 mg/m² intravenous (IV) every 4 weeks  
• Combination treatment: 300 mg/m² IV (plus cyclophosphamide 600 mg/m² IV) every 4 weeks

Dose Modifications

For SI units: Count in US units x 10^6/L

Give full dose if

• Platelets 50-100,000
• Neutrophils 500-2000

Give 125% if

• Platelets above 100000
• Neutrophils above 2000

Give 75% if

• Platelets below 50000
• Neutrophils below 500

Renal Impairment

• Creatinine clearance (CrCl) 41-59 mL/minute: 250 mg/m² IV on day 1
• CrCl 16-40 mL/minute: 200 mg/m² IV on day 1
• CrCl below15 mL/minute: Not recommended

Hepatic Impairment

• Dose adjustment may not be necessary; not studied

Administration

• Do not repeat dose until absolute neutrophil count (ANC) is above 2000 AND platelets above 100000
• Infuse over a period longer than 15 minutes
• Monitor: Complete blood count (CBC) weekly

Other Indications and Uses

Off-label: testicular cancer, head and neck cancer, cervix cancer, small cell lung cancer, progressive diffuse large B-cell lymphoma

Geriatric:

• Calvert formula should be used to calculate dosing

Pediatric:

General Dosing Guidelines

Solid tumor

• 300-600 mg/m² IV every 4 weeks  

Sarcoma (bone/soft tissue)

• 400 mg/m²/day for 2 days every 21 days

Brain tumor

• 175 mg/m² every week for 4 weeks with a 2 weeks recovery period between courses

Bone marrow transplant preparative regimen

• 500 mg/m²/day for 3 days

Retinoblastoma

• 1-2 mL subconjunctival injection of 10 mg/mL solution per dose

Overdose

Carboplatin overdose can cause liver toxicity and severe neutropenia. Overdose treatment includes symptomatic and supportive care and delaying the next carboplatin treatment, if necessary.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Carboplatin has no known severe interactions with other drugs.
• Serious interactions of carboplatin include:
  • adenovirus types 4 and 7 live, oral
  • amphotericin B deoxycholate
  • axicabtagene ciloleucel
  • bacitracin
  • brexucabtagene autoleucel
  • cidofovir
  • ciltacabtagene autoleucel
  • idecabtagene vicleucel
  • influenza virus vaccine quadrivalent, adjuvanted
  • influenza virus vaccine trivalent, adjuvanted
  • lisocabtagene maraleucel
  • palifermin
  • ropeginterferon alfa 2b
  • tisagenlecleucel
  • tofacitinib
• Carboplatin has moderate interactions with at least 58 different drugs.
• Mild interactions of carboplatin include:
  • vitamin A
  • vitamin E

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

• Carboplatin can cause fetal harm if administered during pregnancy. Do not use except in life-threatening emergencies when no safer drug is available.
• Women of pregnancy potential should use effective contraception while receiving carboplatin treatment.
• It is not known if carboplatin is excreted in breast milk. Nursing mothers should discontinue breastfeeding while receiving carboplatin treatment because of the potential for possible toxicity to the breastfed infant.

• You will need frequent tests while on carboplatin treatment, follow up with your healthcare provider and do not miss appointments.
• Inform your physician if you develop infections or have unusual bleeding.