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تعداد آیتم قابل مشاهده باقیمانده : 3 مورد

Systemic therapy regimens for advanced non-small cell lung cancer: Carboplatin plus nanoparticle albumin-bound paclitaxel (nabpaclitaxel)[1]

Systemic therapy regimens for advanced non-small cell lung cancer: Carboplatin plus nanoparticle albumin-bound paclitaxel (nabpaclitaxel)[1]
Cycle length: 21 days.
Drug Dose and route Administration Given on days
Nabpaclitaxel* 100 mg/m2 IV Administer undiluted over 30 minutes. Days 1, 8, 15
Carboplatin AUC = 6 mg/mL per min IV Dilute in 250 mL NSΔ and administer over 30 minutes. The carboplatin should be given immediately after the nabpaclitaxel. Day 1
Pretreatment considerations:
Emesis risk
  • MODERATE on day 1 (30 to 90%); LOW on days 8 and 15 (10 to 30%).◊
  • Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
Prophylaxis for infusion reactions
  • Premedication to prevent hypersensitivity reactions is generally not needed. Premedication may be needed in patients who have had a prior hypersensitivity reaction to nabpaclitaxel.
  • Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
Vesicant/irritant properties
  • Nabpaclitaxel can cause significant tissue damage; avoid extravasation.
  • Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
Infection prophylaxis
  • The incidence of febrile neutropenia with this regimen was 1%.[1] Primary prophylaxis with granulocyte colony stimulating factors is not indicated.
  • 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
  • A lower starting dose for nabpaclitaxel may be needed for patients with liver impairment.[2] Do not administer nabpaclitaxel if AST >10 times ULN or bilirubin >5 times ULN. Each carboplatin dose should be calculated based upon kidney function by use of the Calvert formula.
  • 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 platelets weekly during treatment.
  • Electrolytes, kidney, and liver function weekly during treatment.
  • Monitor for infusion reactions.
  • Monitor for extravasation.
  • Assess for changes in neurologic function prior to each treatment cycle.
Suggested dose modifications for toxicity:
Myelotoxicity
  • Do not administer carboplatin and nabpaclitaxel on day 1 of each new cycle unless ANC is ≥1500/microL and platelet count is ≥100,000/microL.[2,3] For patients who develop neutropenic fever OR ANC <500/microL for >7 days or delay of next cycle by >7 days or thrombocytopenia, withhold treatment until counts recover to an ANC of at least 1500/microL and platelet count of at least 100,000/microL on day 1, or to an ANC of at least 500/microL and platelet count of at least 50,000/microL on days 8 or 15 of the cycle.[2] Upon resumption of therapy, reduce nabpaclitaxel and carboplatin by 25% upon the first occurrence, an additional 25% on the second recurrence, and discontinue treatment for a third occurrence.
Peripheral neuropathy
  • In the original trial, all patients had less than grade 2 peripheral neuropathy prior to beginning therapy.[1] Withhold nabpaclitaxel for grade 3 or 4 neuropathy during treatment. Resume nabpaclitaxel and carboplatin at reduced doses when peripheral neuropathy improves to grade 1 or completely resolves. Upon resumption of therapy, reduce nabpaclitaxel and carboplatin AUC by 25% for the first occurrence of grade 3 or 4 peripheral neuropathy, and an additional 25% for the second occurrence.[2] Discontinue treatment for a third occurrence.[2,3]
Hepatotoxicity
  • Reduced starting doses of nabpaclitaxel are recommended for individuals with pre-existing moderate to severe hepatic impairment; the need for further dose adjustments in subsequent courses based upon ongoing hepatotoxicity should be based on individual tolerance and clinician judgment.[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.
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; AST: aspartate aminotransferase; 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; ULN: upper limit of normal.

* Do not substitute paclitaxel for nabpaclitaxel.

¶ 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 Diluent solutions should not be modified without consulting a detailed reference due to potential incompatibility(ies).

◊ 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.

References:
  1. Socinski MA, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: Final results of a phase III trial. J Clin Oncol 2012; 30:2055.
  2. Abraxane for injectable suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound). United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on October 30, 2019).
  3. Carboplatin injection. United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on October 30, 2019).
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