Carboplatin

Carboplatin Brand Name– Paraplatin

What is Carboplatin

Carboplatin (CBDCA) is a platinum compound related to cisplatin.

Carboplatin is formed by replacing the chloride leaving groups of cisplatin with 1, 1-cyclobutanedicarboxylato ligand, which increases the stability of the leaving groups.

On a molar basis, carboplatin is 45 times less cytotoxic than cisplatin.

Carboplatin has a more favorable adverse effect profile than cisplatin, which has led to the investigation of the replacement of cisplatin with carboplatin in many regimens.

Carboplatin and cisplatin seem to be equally effective in ovarian, non-small cell and small cell lung cancers.

Comparative trials are ongoing in these cancers and others to determine if there is an advantage of carboplatin over cisplatin. Most tumors that are resistant to cisplatin will be resistant to carboplatin.

Currently, there does not seem to be a role for carboplatin in place of cisplatin in the routine management of testicular or head and neck cancers.

Due to its myelosuppressive effects, carboplatin has been used in bone marrow ablation protocols and in the treatment of relapsed leukemias.

The FDA approved carboplatin for the treatment of ovarian cancer in March 1989.

Indications & Dosage

  1. acute lymphocytic leukemia (ALL)
  2. bladder cancer
  3. breast cancer
  4. glioblastoma multiforme
  5. head and neck cancer
  6. malignant glioma
  7. mesothelioma
  8. neuroblastoma
  9. non-Hodgkin’s lymphoma (NHL)
  10. non-small cell lung cancer (NSCLC)
  11. ovarian cancer
  12. small cell lung cancer (SCLC)
  13. stem cell transplant preparation
  14. testicular cancer
  15. thymic carcinoma
  16. thymoma
  17. Wilms’ tumor

Carboplatin Dosing with the Calvert equation:

NOTE: For all equations, AUC (area under the plasma concentration vs. time curve) is expressed in mg/ml x min and GFR (glomerular filtration rate) in ml/min.

The GFR should be calculated using creatinine clearance determined by actual measurements or estimated by using the Cockroft-Gault or Jeliffe methods.

It should be noted that these methods of determining creatinine clearance may not be as accurate, especially in patients with renal dysfunction or patients with low body weight, as the (51)Cr-EDTA method used in the original study. Currently, (51)Cr-EDTA is not available in the United States.

The following are general recommendations for target AUC; however, exact dosing guidelines have not been established and may vary depending upon the disease state and protocol.

  • For chemotherapy naive patients receiving carboplatin: A target AUC of 6—8 mg/ml x min is recommended.
  • For previously treated patients receiving carboplatin alone: An AUC of 4—6 mg/ml x min is recommended.
  • For patients receiving carboplatin with other antineoplastics: An AUC of 4—7 mg/ml x min is recommended.

NOTE: By the end of 2010, all clinical laboratories in the US will use the standardized Isotope Dilution Mass Spectrometry (IDMS) method to measure serum creatinine.

Compared to older methods of measuring serum creatinine, the IDMS method may underestimate serum creatinine when values are relatively low (e.g. about 0.7 mg/dl).

This could result in an overestimation of GFR in patients with normal renal function and when using the Calvert formula for carboplatin dosing, may result in a higher than desired dose and increased drug-related toxicity.

If a patient’s GFR is calculated based on a serum creatinine measured using the IDMS method, the FDA recommends that physicians consider capping the dose of carboplatin for desired exposure to avoid potential overdosing.

Based on the Calvert formula, maximum doses can be calculated as follows:

Target AUC = 6, the maximum dose is 6 x 150 = 900 mg

Target AUC = 5, the maximum dose is 5 x 150 = 750 mg

Target AUC = 4, the maximum dose is 4 x 150 = 600 mg

Maximum dose recommendations are based on a maximum estimated GFR = 125 ml/min. Higher estimated GFR values should not be used.

Side Effects

  1. alopecia
  2. anemia
  3. anemia
  4. anorexia
  5. asthenia
  6. bleeding
  7. bone marrow suppression
  8. bronchospasm
  9. constipation
  10. dehydration
  11. diarrhea
  12. dysgeusia
  13. elevated hepatic enzymes
  14. erythema
  15. hearing loss
  16. heart failure
  17. hemolytic-uremic syndrome
  18. hyperbilirubinemia
  19. hypertension
  20. hypocalcemia
  21. hypokalemia
  22. hypomagnesemia
  23. hyponatremia
  24. hypotension
  25. infection
  26. injection site reaction
  27. leukopenia
  28. leukopenia
  29. nausea
  30. neutropenia
  31. neutropenia
  32. new primary malignancy
  33. pruritus
  34. rash
  35. serious hypersensitivity reactions or anaphylaxis
  36. stomatitis
  37. stroke
  38. thrombocytopenia
  39. thrombocytopenia
  40. thromboembolism
  41. tissue necrosis
  42. urticaria
  43. visual impairment
  44. vomiting

Monitoring Parameters

  • CBC with differential
  • serum calcium
  • serum creatinine/BUN
  • serum magnesium
  • serum phosphate
  • serum potassium
  • serum sodium
  • serum uric acid

Contraindications

  • anemia
  • anuria
  • bleeding
  • bone marrow suppression
  • breast-feeding
  • children
  • coagulopathy
  • dialysis
  • geriatric
  • hearing impairment
  • herpes infection
  • infection
  • neutropenia
  • peripheral neuropathy
  • platinum compound hypersensitivity
  • pregnancy
  • radiation therapy
  • renal failure
  • renal impairment
  • requires a specialized care setting
  • requires an experienced clinician
  • serious hypersensitivity reactions or anaphylaxis
  • thrombocytopenia
  • varicella
  • viral infection
  • vomiting

Interactions

  • Amikacin
  • Aminoglycosides
  • Bictegravir; Emtricitabine; Tenofovir Alafenamide
  • Capreomycin
  • Carbamazepine
  • Clozapine
  • Colistimethate, Colistin, Polymyxin E
  • Daclizumab
  • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
  • Doravirine; Lamivudine; Tenofovir disoproxil fumarate
  • Efavirenz; Emtricitabine; Tenofovir
  • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
  • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
  • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
  • Emtricitabine; Rilpivirine; Tenofovir alafenamide
  • Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate
  • Emtricitabine; Tenofovir alafenamide
  • Emtricitabine; Tenofovir disoproxil fumarate
  • Ethotoin
  • Fosphenytoin
  • Gentamicin
  • Hydantoins
  • Kanamycin
  • Lamivudine; Tenofovir Disoproxil Fumarate
  • Mycophenolate
  • Paclitaxel
  • Palifermin
  • Paromomycin
  • Penicillamine
  • Phenytoin
  • Plazomicin
  • Polymyxin B
  • Polymyxins
  • Sirolimus
  • Streptomycin
  • Tacrolimus
  • Tenofovir Alafenamide
  • Tenofovir Alafenamide
  • Tenofovir, PMPA
  • Tobramycin
  • Tuberculin Purified Protein Derivative, PPD
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