Chemotherapy regimens for chemotherapy-naïve extensive-stage small cell lung cancer: Carboplatin plus etoposide^[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 topics on prevention of chemotherapy-induced nausea and vomiting in adults.
Vesicant/irritant properties	Carboplatin and etoposide are irritants. Refer to UpToDate topics 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 topics 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 kidney dysfunction	Each carboplatin dose should be calculated based upon kidney function by use of the Calvert formula.* A lower starting dose of etoposide may be needed for patients with kidney or liver impairment.^[2] Refer to UpToDate topics on chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents; 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 kidney 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 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.
Nephrotoxicity	Alterations in kidney function during therapy may require a recalculation of the carboplatin dose. Refer to UpToDate topics 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.

ANC: absolute neutrophil count; AUC: area under the concentration × time curve; CBC: complete blood count; D5W: 5% dextrose in water; GFR: glomerular filtration rate; IV: intravenous; NCCN: National Comprehensive Cancer Network; NS: normal saline.

* 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 topics 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 topics on prevention and treatment of chemotherapy-induced nausea and vomiting in adults.

References:

Socinski MA, Smit EF, Lorigan P, et al. Phase III study of pemetrexed plus carboplatin compared with etoposide plus carboplatin in chemotherapy-naive patients with extensive-stage small-cell lung cancer. J Clin Oncol 2009; 27:4787.
Etoposide injection. United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on October 29, 2019).

Graphic 75586 Version 27.0

خرید پکیج

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

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