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تعداد آیتم قابل مشاهده باقیمانده : -73 مورد

Systemic therapy regimens for non-small cell lung cancer and mesothelioma: Pemetrexed plus carboplatin[1,2]

Systemic therapy regimens for non-small cell lung cancer and mesothelioma: Pemetrexed plus carboplatin[1,2]
Cycle length: Every 21 days for a maximum of four cycles.
Drug Dose and route Administration Given on days
Pemetrexed 500 mg/m2 IV Dilute with 100 mL NS* and administer over 10 minutes. Do not administer with calcium-containing IV fluids such as lactated Ringer solution. Day 1
Carboplatin AUC = 5 mg/mL × min IV Dilute in 250 mL NS* and administer over 30 minutes, beginning 30 minutes after pemetrexed. Day 1
Pretreatment considerations:
Emesis risk
  • MODERATE.Δ
  • Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
Prophylaxis for skin rashes
  • Premedication with dexamethasone (4 mg orally twice daily for three days starting the day before drug administration) is recommended to reduce cutaneous toxicity.[3]
  • Refer to UpToDate topics on cutaneous complications of conventional chemotherapy agents.
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 8% but may be higher in patients 75 years of age and older.[1] The decision to use primary prophylaxis with a hematopoietic growth factor 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
  • Avoid use of pemetrexed if CrCl is <45 mL/min. Each carboplatin dose should be calculated based upon kidney function by use of the Calvert formula. There are recommendations for avoidance of NSAIDs in the days prior to and immediately following each dose of pemetrexed in patients with mild to moderate kidney dysfunction (CrCl 45 to 79 mL/min) because of the potential for decreased clearance of pemetrexed.
  • 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; dosing of anticancer agents in adults; and pemetrexed: drug information.
Vitamin supplementation
  • Vitamin supplementation with folic acid and B12 is recommended prior to administration of pemetrexed and during treatment to reduce both hematologic and nonhematologic side effects.[3]
Monitoring parameters:
  • CBC with differential and platelet count before each treatment and once midcycle between days 10 to 14.
  • Electrolytes, kidney, and liver function before 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. Dose reductions should be maintained for subsequent cycles.[1]
Nonhematologic toxicity§
  • Creatinine clearance should be ≥45 mL/min, and grade 3 and 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 is ≤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, for 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. 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; CrCl: creatinine clearance; GFR: glomerular filtration rate; IV: intravenous; NCCN: National Comprehensive Cancer Network; NS: normal saline; NSAIDs: nonsteroidal anti-inflammatory drugs.

* Diluent solutions should not be modified without consulting a detailed reference due to potential incompatibility(ies). There is also the option of a ready-to-use formulation of pemetrexed that requires no reconstitution, dilution, or refrigeration.[3]

¶ 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 topic 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 topic on "Prevention and treatment 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.[3,4]

§ Toxicity was graded using the Common Terminology Criteria of Adverse Events version 3.0.
References:
  1. Gronberg BH, Bremnes RM, Flotten 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.
  2. Ceresoli GL, Zucali PA, Favaretto AG, et al. Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. J Clin Oncol 2006; 24:1443.
  3. Pemetrexed disodium injection. United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on March 15, 2024).
  4. Carboplatin 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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