Chemotherapy regimens for non-small cell lung cancer: Gemcitabine plus carboplatin^[1]

Cycle length: Every 21 days for a maximum of four cycles.
Drug	Dose and route	Administration	Given on days
Gemcitabine	1000 mg/m² IV	Dilute in 250 mL NS* (concentration no more than 40 mg/mL) and administer over 30 to 60 minutes.	Days 1 and 8
Carboplatin	AUC^¶ = 5 mg/mL × min IV	Dilute in 250 mL NS* and administer over 30 minutes.	Day 1
Pretreatment considerations:
Emesis risk	MODERATE on day 1 and LOW on day 8.^Δ Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
Vesicant/irritant properties	Carboplatin is an irritant. Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
Infection prophylaxis	The incidence of neutropenic infections was reported to be 9% but may be higher in patients 75 years of age or older.^[1] Decisions about primary prophylaxis with hematopoietic growth factors should be individualized according to current guidelines. 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 gemcitabine may be needed for patients with liver impairment. 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 on days 1 and 8 of each cycle during treatment.
Electrolytes, kidney, and liver function on day 1 of each cycle.
Suggested dose modifications for toxicity:^◊
Myelotoxicity	Chemotherapy should be delayed for one week if the ANC is <1000/microL and/or the platelet count is <75,000/microL prior to the start of each cycle. Doses for subsequent cycles are reduced by 25% if the ANC is 1000 to 1499/microL or platelets are 75,000 to 99,000/microL on day 22 after the preceding cycle, or if the nadir ANC was <500/microL. A 50% dose reduction should be considered if the platelet nadir is <50,000/microL. Consider discontinuing therapy if a patient qualifies for a third dose reduction or a cycle is delayed by more than 21 days. Omissions or reductions of the gemcitabine dose on day 8 of a cycle are allowed and are based upon the same criteria as on day 1. Dose reductions should be maintained for subsequent cycles.^[1]
Thrombotic microangiopathy	Thrombotic microangiopathy (TMA, also sometimes called thrombotic thrombocytopenic purpura [TTP] or hemolytic uremic syndrome [HUS]) has been associated with gemcitabine, in individuals who have received a large or small cumulative dose.^[2] Consider the possibility of TMA if the patient develops Coombs-negative hemolysis, thrombocytopenia, kidney failure, and/or neurologic findings. Management consists of drug discontinuation and supportive care, without plasma exchange, as long as there is high confidence in a drug-induced etiology rather than TTP. Refer to UpToDate topics on drug-induced thrombotic microangiopathy.
Pulmonary toxicity	A variety of manifestations of pulmonary toxicity have been reported. Discontinue gemcitabine immediately and permanently. Refer to UpToDate topics on pulmonary toxicity associated with antineoplastic therapy, cytotoxic agents.
Other nonhematologic toxicity^§	Creatinine clearance should be ≥45 mL/min and grade 3 or 4 toxicities should be resolved prior to beginning therapy. A delay in therapy by one week should be considered if toxicities are not resolved or the creatinine clearance ≤45 mL/min. It is recommended that subsequent cycles be dose reduced by 25% if the patient has grade 3 or 4 toxicity (excluding grade 3 or 4 mucositis, in which a 50% dose reduction is warranted) and discontinued if a patient qualifies for a third dose reduction or a cycle is delayed by more than 21 days. Omissions or reductions of the gemcitabine dose on day 8 of a cycle are allowed. Dose reductions should be maintained for subsequent cycles.^[1]
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; GFR: glomerular filtration rate; IV: intravenous; NCCN: National Comprehensive Cancer Network; NS: normal saline.

* Diluent solutions should not be modified without consulting a detailed reference due to potential incompatibility(ies).
¶ AUC is converted to a patient-specific carboplatin dose (in mg) according to kidney 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.
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 of chemotherapy-induced nausea and vomiting in adults.
◊ Dose adjustments in the study may differ slightly from that recommended by the manufacturer. The manufacturer's recommendations can be found in the United States Prescribing Information.^[2,3]
§ Toxicity was graded using the Common Terminology Criteria of Adverse Events version 3.0.

References:

Gronberg BH, Bremnes RM, Fløtten O, et al. Phase III study by the Norwegian lung cancer study group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2009; 27:3217.
Gemcitabine hydrochloride injection. United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on October 28, 2019).
Carboplatin 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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Chemotherapy regimens for non-small cell lung cancer: Gemcitabine plus carboplatin[1]

Chemotherapy regimens for non-small cell lung cancer: Gemcitabine plus carboplatin^[1]