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Paclitaxel and carboplatin chemotherapy for non-small cell lung cancer[1]

Paclitaxel and carboplatin chemotherapy for non-small cell lung cancer[1]
Cycle length: Every 21 days, for a maximum of six cycles.
Drug Dose and route Administration Given on days
Paclitaxel 200 mg/m2 IV Dilute in 250 mL NS* and administer over one hour; special tubing needed. Day 1
Carboplatin AUCΔ = 6 mg/mL per min IV Dilute in 250 mL NS* and administer over 30 minutes. Day 1
Pretreatment considerations:
Emesis risk
  • MODERATE.◊
  • Refer to UpToDate topic on "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults".
Prophylaxis for infusion reactions
  • Premedicate with dexamethasone plus both an H1 and an H2 receptor antagonist prior to paclitaxel administration.
  • Refer to UpToDate topic on "Infusion reactions to systemic chemotherapy".
Vesicant/irritant properties
  • Paclitaxel can cause significant tissue damage; avoid extravasation.
  • Refer to UpToDate topic on "Extravasation injury from chemotherapy and other non-antineoplastic vesicants".
Infection prophylaxis
  • Primary prophylaxis with hematopoietic growth factors is not recommended (risk of febrile neutropenia approximately 2 to 4%[1]).
  • Refer to UpToDate topic on "Use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation".
Dose adjustment for baseline liver or renal dysfunction
  • Each carboplatin dose should be calculated based upon renal function by use of the Calvert formula.Δ
  • A lower starting dose of paclitaxel may be needed in patients with liver impairment.
  • Refer to UpToDate topics on "Chemotherapy hepatotoxicity and dose modification in patients with liver disease: Conventional cytotoxic agents" and "Chemotherapy hepatotoxicity and dose modification in patients with liver disease: Molecularly targeted agents" and "Dosing of anticancer agents in adults".
Monitoring parameters:
  • CBC with differential weekly during treatment.
  • Serum electrolytes and liver and renal function tests prior to each treatment cycle.
  • Assess changes in neurologic function prior to each treatment cycle.
Suggested dose modifications for toxicity:
Myelotoxicity
  • Treatment with paclitaxel and carboplatin should be delayed until the absolute neutrophil count is >1500/microL and platelet count is >100,000/microL. If a patient developed severe neutropenia (<500/microL) for a week or longer, or febrile neutropenia during the prior course, then the paclitaxel and carboplatin doses should be reduced by 20 to 25% for subsequent courses.[2] An alternative to dose reduction is the institution of hematopoietic growth factor support. The carboplatin dose should be decreased by 25% in patients whose platelet count nadir is <50,000/microL for longer than five days.[3]
Renal/hepatic toxicity
  • Alterations in renal function during therapy may require a recalculation of the carboplatin dose. Paclitaxel dose may need to be adjusted for hepatic impairment on day 1 of each cycle.
  • Refer to UpToDate topics on "Dosing of anticancer agents in adults" and "Chemotherapy hepatotoxicity and dose modification in patients with liver disease: Conventional cytotoxic agents" and "Chemotherapy hepatotoxicity and dose modification in patients with liver disease: Molecularly targeted agents".
Neurotoxicity
  • For patients who develop severe neuropathy (grade 3 or 4) for a week or longer, the dose of paclitaxel should be reduced by 20% for subsequent courses.[4]
If there is a change in body weight of at least 10%, doses should be recalculated.
Dose reductions may also be indicated if there are other grade 2 or higher nonhematologic toxicities. The dose reduction is at the discretion of the clinician, as formal guidelines are not available.
This table is provided as an example of how to administer this regimen; there may be other acceptable methods. This regimen must be administered by a clinician trained in the use of chemotherapy, who should use independent medical judgment in the context of individual circumstances to make adjustments, as necessary.
IV: intravenous; NS: normal saline; AUC: area under the concentration × time curve; CBC: complete blood count; D5W: 5% dextrose in water; NCCN: National Comprehensive Cancer Network; GFR: glomerular filtration rate.
* Diluent solutions should not be modified without consulting a detailed reference due to potential incompatibility(ies).
¶ Paclitaxel can be administered in NS, D5W, or NS/D5W* at varying concentrations between 0.3 to 1.2 mg/mL. Use glass or polypropylene bottles or polypropylene or polyolefin plastic bags, and administer through polyethylene-lined administration sets with a microporous membrane 0.22 microns or less.
Δ AUC is converted to a patient-specific carboplatin dose (in mg) according to renal function by using the Calvert formula. The Calvert formula is total dose (mg) = (target AUC) × (GFR + 25). If using measured serum creatinine, limit the maximal GFR for the calculation to 125 mL/min. Refer to UpToDate topic on "Dosing of anticancer agents in adults".
◊ Consensus-based guidelines from the NCCN classify higher carboplatin doses (AUC ≥4) as highly emetogenic; by contrast, the American Society of Clinical Oncology and the Multinational Association for Supportive Care in Cancer guidelines consider all carboplatin doses to be moderately emetogenic. Although many institutions classify carboplatin-containing regimens as moderately emetogenic, a benefit for adding a neurokinin 1 receptor antagonist on day 1 has been shown in many studies; additional prophylaxis beyond day 1 for delayed emesis is not needed for most patients. Refer to UpToDate topic on "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults".
References:
  1. Sandler A, et al. N Engl J Med 2006; 355:2542.
  2. Langer CT, et al. J Clin Oncol 1995; 13:1860.
  3. Carboplatin injection. United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on October 28, 2019).
  4. Paclitaxel injection. United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on October 28, 2019).
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