Advanced Disease Regimen: Carboplatin + Paclitaxel
Hauschild A et al. J Clin Oncol 2009;27:2823–2830
Premedications:
Dexamethasone 20 mg per dose; administered orally or intravenously for 2 doses: the first dose between 12 and 14 hours before starting paclitaxel, and a second dose 6–7 hours before starting paclitaxel
Diphenhydramine 50 mg; administer intravenously per push 30 minutes before starting paclitaxel
Ranitidine 50 mg; administer intravenously in 25–100 mL of 0.9% sodium chloride injection (0.9% NS) or 5% dextrose injection (D5W) over 15–30 minutes, 30–60 minutes before starting paclitaxel
Cycles 1 through 4
Paclitaxel 225 mg/m2; administer intravenously, diluted in 0.9% sodium chloride injection (0.9% NS) or 5% dextrose injection (D5W) to a concentration between 0.3 and 1.2 mg/mL, over 3 hours before carboplatin on day 1, every 21 days cycle (total dosage/cycle = 225 mg/m2)
Carboplatin AUC = 6 mg/mL · min✫; administer intravenously, diluted in 0.9% NS or D5W to a concentration >0.5 mg/mL, over 30 minutes on day 1 every 21 days (total dose/cycle calculated to produce an AUC = 6 mg/mL · min✫)
Cycles 5 through 10
Paclitaxel 175 mg/m2; administer intravenously, diluted in 0.9% NS or D5W to a concentration between 0.3 and 1.2 mg/mL, over 3 hours on day 1, every 21 days (total dosage/cycle = 175 mg/m2)
Carboplatin AUC = 5 mg/mL · min✫; administer intravenously, diluted in 0.9% NS or D5W to a concentration >0.5 mg/mL, over 30 minutes on day 1, every 21 days (total dose/cycle calculated to produce an AUC = 5 mg/mL · min✫)

In practice, creatinine clearance (Clcr) is used in place of glomerular filtration rate (GFR). Clcr can be estimated from the equation of Cockcroft and Gault, thus:

Note: A carboplatin dose calculated with an IDMS-measured serum creatinine result using the Calvert formula could exceed an expected exposure (AUC) and result in increased drug-related toxicity. The FDA recommends capping an estimated GFR at 125 mL/min for any targeted AUC value. No greater estimated GFR values should be used [online] May 23, 2013. Available from: http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm228974.htm [accessed February 26, 2014]
Notes:
If paclitaxel is discontinued because of hypersensitivity, carboplatin may be continued
If carboplatin is discontinued because of hypersensitivity, tinnitus, or hearing loss, paclitaxel may be continued
After 4 cycles of chemotherapy, the dose of both chemotherapy agents will be reduced to carboplatin AUC of = 5 mg/mL · min and paclitaxel 175 mg/m2. Patients who had a dose reduction during the first 4 chemotherapy cycles will continue at reduced doses. There is no additional dose reduction at cycle 5; a second dose reduction would be triggered by an occurrence of toxicity
In the absence of unacceptable toxicity, patients may continue to receive chemotherapy until disease progression. After completing 10 cycles of chemotherapy, carboplatin and paclitaxel may be discontinued at the discretion of a treating physician
Supportive Care
Antiemetic prophylaxis
Emetogenic potential is HIGH with potential for delayed symptoms
See Chapter 39 for antiemetic recommendations
Hematopoietic growth factor (CSF) prophylaxis
Primary prophylaxis is indicated with one of the following:
Filgrastim (G-CSF) 5 mcg/kg per day by subcutaneous injection, or
Pegfilgrastim (pegylated filgrastim) 6 mg/0.6 mL by subcutaneous injection for 1 dose
See Chapter 43 for more information
Antimicrobial prophylaxis
Risk of fever and neutropenia is LOW
See Chapter 47 for more information
Patient Population Studied
A study of 270 patients with unresectable stages III/IV melanoma with disease progression on a dacarbazine- or temozolomide-containing regimen. Prior adjuvant immunotherapy was allowed. Patients with active brain metastases were excluded