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Carboplatin plus etoposide for chemotherapy-naïve extensive-stage small cell lung cancer[1]

Carboplatin plus etoposide for chemotherapy-naïve extensive-stage small cell lung cancer[1]
Cycle length: 21 days, for a maximum of six cycles.
Drug Dose and route Administration Given on days
Carboplatin AUC* = 5 mg/mL × min IV Dilute in 250 mL NS and administer over 30 minutes. Day 1
Etoposide 100 mg/m2 IV Dilute in 500 mL NS or D5W to final concentration <0.4 mg/mL. Infuse over 30 to 60 minutes; if infused more rapidly, severe hypotension may occur. Days 1, 2, and 3
Pretreatment considerations:
Emesis risk
  • MODERATE on day 1 and LOW on days 2 and 3.Δ
  • Refer to UpToDate topic on "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults".
Vesicant/irritant properties
  • Carboplatin and etoposide are irritants.
  • Refer to UpToDate topic on "Extravasation injury from chemotherapy and other non-antineoplastic vesicants".
Infection prophylaxis
  • Routine primary prophylaxis with hematopoietic growth factors is not recommended (incidence of febrile neutropenia is about 5%[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.* A lower starting dose of etoposide may be needed for patients with renal or liver impairment.[2]
  • 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 and platelet count weekly during treatment.
  • Electrolytes and liver and renal function prior to each cycle of chemotherapy.
Suggested dose modifications for toxicity:
Myelotoxicity
  • Dose adjustment based on myelotoxicity was not reported in the final publication. Per protocol, cycles were delayed for up to 42 days to allow neutrophils to return to ≥1500/microL and platelets to ≥100,000/microL.[1] However, the United States Prescribing Information recommends that the dose of carboplatin be reduced by 25% if platelets are <50,000/microL and/or ANC is <500/microL.
Nonhematologic toxicity
  • Chemotherapy should be held for grade 3 and 4 nonhematologic toxicities (except for neurotoxicity) and is only restarted after the toxicity has resolved to patient's baseline.[1]
Hepatotoxicity
  • No formal etoposide dosing recommendations were reported in this publication. However, accepted dose reductions per product information may be found in the literature.
  • Refer to UpToDate topic 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".
Nephrotoxicity
  • Alterations in renal function during therapy may require a recalculation of the carboplatin dose.
  • Refer to UpToDate topic on "Dosing of anticancer agents in adults".
If there is a change in body weight of at least 10%, doses should be recalculated.
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.
AUC: area under the concentration × time curve; IV: intravenous; NS: normal saline; D5W: 5% dextrose in water; CBC: complete blood count; ANC: absolute neutrophil count; GFR: glomerular filtration rate; NCCN: National Comprehensive Cancer Network.
* 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".
¶ Diluent solutions should not be modified without consulting a detailed reference due to potential incompatibility(ies).
Δ 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. Socinski MA, et al. J Clin Oncol 2009; 27:4787.
  2. Etoposide injection. United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on October 29, 2019).
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